Next Article in Journal
Recombinant Inga Laurina Trypsin Inhibitor (ILTI) Production in Komagataella Phaffii Confirms Its Potential Anti-Biofilm Effect and Reveals an Anti-Tumoral Activity
Next Article in Special Issue
Zoonotic Fecal Pathogens and Antimicrobial Resistance in Canadian Petting Zoos
Previous Article in Journal
Harnessing the Power of Microbiome Assessment Tools as Part of Neuroprotective Nutrition and Lifestyle Medicine Interventions
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Microorganisms
Volume 6
Issue 2
10.3390/microorganisms6020036
microorganisms-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Genotypic Features of Clinical and Bovine Escherichia coli O157 Strains Isolated in Countries with Different Associated-Disease Incidences

by
Luis Pianciola
1,* and
Marta Rivas
2
1
Laboratorio Central, Subsecretaría de Salud de Neuquén, Gregorio Martínez 65, Neuquén 8300, Argentina
2
Servicio Fisiopatogenia, INEI-ANLIS “Carlos G. Malbrán”, Av. Vélez Sarsfield 563, Buenos Aires 1281, Argentina
*
Author to whom correspondence should be addressed.
Microorganisms 2018, 6(2), 36; https://doi.org/10.3390/microorganisms6020036
Submission received: 28 March 2018 / Revised: 20 April 2018 / Accepted: 25 April 2018 / Published: 27 April 2018
(This article belongs to the Special Issue Pathogenesis of Enterohaemorrhagic Escherichia coli)
Versions Notes

Abstract

:
There is great geographical variation in the frequency of Escherichia coli O157 infections that correlates with important differences in the bovine reservoir of each country. Our group carried out a broad molecular characterization of human and bovine E. coli O157 strains circulating in Argentina using different methodologies. Our data allows us to conclude that in Argentina, a high homogeneity is observed in both cattle and human strains, with almost exclusive circulation of strains belonging to the hypervirulent clade 8 described by Manning. The aim of this review was to compare the genetic background of E. coli O157 strains isolated in countries that have conducted similar studies, to try to correlate specific O157 genotypes with the incidence and severity of E. coli O157 associated diseases. The characteristics of the strains that cause disease in humans reflect the predominant genotypes in cattle in each of the countries analyzed. The main features clearly linked to high incidence or severity of E. coli O157 infections are lineage-specific polymorphism assay-6 lineage I/II, clade 8 strains and probably, clade 6 strains, the stx2a/stx2c genotype, the presence of q933 and q21 simultaneously, and putative virulence factor EC_3286. In countries with an absence of these features in O157 strains, the overall incidence of O157 disease is low. Argentina, where these characteristics are detected in most strains, shows the highest incidence of hemolytic uremic syndrome (HUS) worldwide.

1. Introduction

Shiga toxin-producing Escherichia coli (STEC) are a heterogeneous group of foodborne pathogens, and E. coli O157:H7 is the most common member of this group. The first outbreak associated with this microorganism occurred in Oregon and Michigan, United States (US), in 1982. It was isolated from individuals with bloody diarrhea and severe abdominal cramps who had consumed beef burgers in a well-known food chain [1]. A retrospective search of this serotype in culture collections showed few positive results—only eight strains were deposited before 1982, one in the US, one in the United Kingdom and six in Canada [2]. This low number of O157 strains could be related to a recent emergence of the pathogen and its entry into the agrifood chain.
E. coli O157 infections can range from asymptomatic carriage to mild diarrhea, hemorrhagic colitis or hemolytic uremic syndrome (HUS), a severe extraintestinal disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure [3]. Between 3% and 9% of STEC infections progress to HUS [4], and the mortality rate is 3–5% with long-term morbidity occurring in approximately 30% of patients [5]. Enterohemorrhagic E. coli (EHEC) is a subgroup of STEC strains characterized as stx/eae positive and recognized by their ability to cause severe disease in humans, like HUS. E. coli O157:H7 is the most frequent EHEC serotype, but other non-O157 EHEC serogroups are also implicated in HUS [6]. Many countries that use only culture-based confirmation of HUS cases, focusing on sorbitol-nonfermenting strains, may miss non-O157 isolates and therefore, bias the reports on the incidence of each serotype.
Majowicz et al. [7] estimated that STEC causes 2,801,000 acute illnesses and leads to 3890 cases of HUS and 230 deaths annually, worldwide. Important differences exist in the incidence of E. coli O157 infections and HUS. Surveillance practices vary considerably, and therefore, caution is required when comparing STEC incidence rates among countries. The incidence of E. coli O157 infections per 100,000 inhabitants is approximately 1.0 in the US, 2.1 in England, 0.43 in Germany and 0.08 in France [8]. There are also important regional differences within each country. For example, cases in Scotland increase from west to east and from north to south [9]. In Argentina, where post-diarrheal HUS is endemic, around 400 new cases are reported each year. The disease is the leading cause of acute renal failure in children and the second most frequent cause of chronic renal failure [10]. During 2016, 356 HUS cases were notified to the National Health Surveillance System, which corresponds to a rate of 0.82 cases per 100,000 inhabitants [9]. During the last decade, the annual incidence has ranged from 8 to 12 cases per 100,000 children under 5 years of age [11]. The distribution of cases shows a marked difference between the different regions of the country. The Northern regions show rates below the national average (0.17 and 0.52 per 100,000 inhabitants for northeast and northwest, respectively), the central region is near the national average (0.89 per 100,000), while central Cuyo (1.08 per 100,000) and particularly the Southern region (1.31 per 100,000) have the highest rates in the country.
Ruminants, especially cattle have been recognized as the main reservoir for E. coli O157 [12], and many studies have shown large variations in its prevalence in livestock [11]. Sheep, and possibly goats, may be other reservoirs [13]. These animals are not affected by this organism. It can also be found in asymptomatic bisons and cervids, and other mammals, like pigs, camelids, rabbits, horses, dogs and cats. Other free-living wild species, like raccoons, opossums, and rats, may carry this organism in their intestinal tract [14]. E. coli O157:H7 may be detected in wild or domesticated birds, including chickens, turkeys, geese, pigeons, starlings, and many other species. Some studies have examined a possible relationship between wild birds and livestock suggesting a role of wild birds in disseminating E. coli O157:H7 strains from feedlot pens to the environment [15]. In some instances, it is difficult to prove whether a species is actually a maintenance host or just a temporary carrier [14]. The foods involved are quite variable and include hamburgers, preparations with different types of meat, sausages, dairy products, cider, lettuce, spinach and vegetable sprouts, among others. A study conducted in the UK, Ireland, Denmark, Norway, Finland, the US, Canada and Japan found that the sources of transmission of E. coli O157 during outbreaks were different foods (42.2% of cases), dairy products (12.2%), contact with animals (7.8%), water (6.7%), the environment (2.2%), and those of unknown origin (28.9%) [16,17]. Transmission from person-to-person, a process that is especially linked to children’s daycare facilities or nurseries, has also been described. Domestic transmission is more frequent in children under 4 years of age [18].
Genomic studies have allowed researchers to postulate an evolutionary step-by-step model from a non-toxigenic sorbitol fermenter precursor related to the enteropathogen, E. coli O55:H7. This ancestor carries the genes of enterocyte effacement, which mediates the intimate attachment of the bacterium to the intestinal epithelium. The first evolutionary steps were the acquisition of the gene coding for Shiga toxin type 2, followed by the somatic antigen switch from O55 to O157 and the acquisition of the large virulence plasmid, pO157. Finally, these strains lost the ability to ferment sorbitol and acquired genes encoding Shiga toxin 1 [19]. Another lineage retained the sorbitol positive phenotype but lost motility, giving rise to the German O157:H- clone [14]. These strains have emerged as important causes of human disease in continental Europe [20]. Bacteriophages have played important roles in the genome changes of E. coli O157, and their genes have been gained and lost very dynamically and quickly [21]. The analysis of Single Nucleotide Polymorphisms (SNP) in stable regions of the genome of both ancestral and current strains from different continents and different sources has shown that the strains are very similar. This may be related to a recent origin of E. coli O157 [22]. The O157 genome has a 5.5 Mb size and includes a 4.1 Mb backbone shared with most of the E. coli serotypes. The rest of the genome originates, largely, from the horizontal transfer of genes, mainly through bacteriophages [23]. The gains and losses of phage genes along with the variation in nucleotides throughout the genome have guided the evolution and diversity of this pathogen [21].
The EDL933 strain associated with the Michigan outbreak and the Sakai City strain were the first E. coli O157:H7 genomes to be sequenced [23,24]. At present, a large number of O157:H7 strains have been sequenced, and whole genome comparisons can provide new insight into the underlying epidemiology of this pathogen. In the near future, the application of whole-genome sequencing (WGS) techniques to the analysis of large E. coli O157 strain collections will become an invaluable tool for molecular subtyping and will facilitate the establishment of evolutionary relationships [25].
Clinical strains of E. coli O157 are characterized by the presence of a specific set of genes and include those coding for Shiga toxins (stx1, stx2), intimin (eae), and hemolysin (ehxA) [26]. There are several subtypes of Stx1 (Stx1a, Stx1c, Stx1d) and Stx2 (Stx2a, Stx2b, Stx2c, Stx2d, Stx2e, Stx2f and Stx2g) [27]. Most human isolates of E. coli O157 produce Stx1, Stx2a or Stx2c alone or in combination with other subtypes. Strains that produce Stx2 are more virulent and are more frequently related to severe diseases [28], and those harboring the stx2a gene cause more serious illnesses than strains carrying stx2c.
There is a clear geographical difference in the incidence and severity of infections due to E. coli O157. For example, the incidence is generally higher in Scotland than in the rest of European countries [8]. In Latin America, the incidence of HUS is very high in Argentina and lower in the rest of the countries of the region. These differences could be due to (i) the different prevalences of cattle colonization; (ii) the load of E. coli O157 in the environment; (iii) the proportion of humans living in areas of high cattle density; (iv) different feeding habits; (v) different genetic structures of pathogen populations; (vi) the pathogen survival in different food types and ecological niches; (vii) differences in genotypes as well as in the infectivity and virulence of circulating strains; or (viii) a combination of these factors [29,30]. The proportion of clinical genotypes in cattle is weakly related to the incidence of HUS in each country, but this is not enough to explain the differences in the international incidence of HUS [24].
A meta-analysis conducted by Salim et al. [31], including 140 studies from 38 countries with more than 220,000 cattle, established a global prevalence of E. coli O157 of 5.68% (95% CI, 5.16–6.20). The study showed great regional variation; the highest prevalence was in Africa (31.20%), followed by North America (7.35%), Oceania (6.85%), Europe (5.15%), Asia (4.69%), and the lowest prevalences were detected in Latin America and the Caribbean (1.65%). Large differences were found between the prevalence in feedlot cattle (19.58%, CI 15.57–23.59) and dairy cattle (1.75%, CI 1.26–2.24). Several studies carried out in Argentina have shown prevalences ranging from 0.21% (CI 0.04–0.61) to 4.07% (CI 2.82–5.67) [32,33,34,35,36]. These data show that in Argentina, the country with the highest HUS incidence worldwide, the frequency of cattle colonization with E. coli O157 is close to the world’s average and is lower than in many other places with low rates of disease. Therefore, this does not seem to be relevant data to explain the geographical differences in the severity of the associated diseases.
Although cattle and other ruminants are the natural reservoir of E. coli O157, only a small subset of serotypes present in animals is related to human diseases [37]. Furthermore, genetic subtypes or lineages of E. coli O157 are more associated with human disease, and others are frequent in animals but rare in humans. This could be related to a low virulence or transmissibility to humans of some E. coli O157 bovine genotypes [38]. Genes of E. coli O157 that encode virulence factors (including products of LEE and pO157) have shown increased expression in clinical genotypes, while genes related to acid resistance and stress fitness were shown to be relatively upregulated in bovine-biased genotypes [39]. Most cattle isolates harbor stx2c as the sole gene encoding Stx, whereas stx2a is more frequent in patients with severe symptoms [33]. The E. coli O157 strains associated with cattle show a pronounced difference in their geographical distribution. This different geographical distribution may have several causes: (a) a different production type or system, like dairy herds or feedlots; (b) age, with a higher prevalence among young animals; (c) season, through an increase in the warmer months of the year; and (d) diet may also affect E. coli O157 populations [40,41]. This regional association suggests that strains of E. coli O157 have diverged evolutionary in different parts of the world through founder effects or genetic drift or by selective regional pressures. In this way, the difference in the virulence of the strains of each geographical area could explain the differences in the incidence and severity of human diseases related to this microorganism [33,39]. Several researchers have identified genetic markers that are found in different frequencies in strains of clinical cases and animals. Some studies have shown that these genotypic differences are attributable to insertions of bacteriophages, deletions and duplications of DNA fragments of different sizes [42,43]. Initially, an octamer-based genomic scanning was used, through which two lineages were identified: lineage I, composed mainly of strains of clinical origin; and lineage II, composed of strains of animal origin [44]. Subsequently, a new technique was developed, lineage-specific polymorphism assay-6 (LSPA-6), based on the use of a multiplex PCR to detect alleles from six loci that identify lineages I and II [45]. In 2010, Zhang et al. [46] identified another lineage, I/II, with intermediate characteristics between lineages I and II. They also showed that strains from lineage I and I/II produce more Stx2 than strains of lineage II, regardless of their origin. Furthermore, lineage I/II has been related to more severe pathologies, such as HUS [47]. It is interesting to note that the distribution of LSPA-6 lineages in human and cattle isolates is very different in The Netherlands, the US and Japan. A similar pattern occurs when other countries or regions are analyzed.
There is also a great variability in the clinical presentation of pathologies caused by E. coli O157. These differences are even more striking when comparing the number of HUS cases and hospitalization rates during different outbreaks. For example, HUS and hospitalization rates during the spinach outbreak in the US in 2006 [48] were higher than those of previous outbreaks in the US [49] and those of the 1996 outbreak in Japan [50]. Manning et al. [51] postulated the existence of E. coli O157 strains with great variation in their virulence and suggested that this diversity could explain the different incidences of severe diseases observed during outbreaks. Phylogenetic studies, based on the analysis of SNP in 36 loci of strains from different outbreaks, allowed the description of nine clades. Within them, clade 8 was related to a high number of HUS cases and the highest rates of hospitalization. For that reason, it is known as the hypervirulent clade.
Kulasekara et al. [52] sequenced the complete genome of strain TW14359 related to the spinach outbreak of 2006. The analysis of this sequence and its comparison with the sequences of other E. coli O157 strains already sequenced (EDL933, from the US outbreak in 1982 and Sakai, from the 1996 outbreak in Japan) identified some characteristic genetic determinants that could be related to the high virulence of this strain. These putative virulence factors include ECSP_0242, which encodes a factor linked to protein–protein interactions; ECSP_2687, which encodes a protein that reduces the expression of cytokines, decreasing the immune response of the host; ECSP_3620, which encodes the anaerobic nitric oxidase, NorV; ECSP_3286, a protein that binds with high affinity to heme; ECSP_1773, which encodes a protein that interferes with the innate immune response and ECSP_2870/2872, which encodes a protein related to adaptation to plant hosts. The presence of the intact norV gene (ECSP_3620) combined with any of the other virulence factors may contribute to the high virulence of these strains.
Although the increased production of Stx2 is a characteristic of clade 8 strains, it is not unique to it and, in addition, not all strains of this clade express high levels of Stx2. The differences in the severity of infections caused by strains of different clades could be explained, at least in part by the differential production of Stx2. In addition, clade 8 strains overexpress LEE genes. Therefore, the virulence of the strains of this clade probably reflects the upregulation of several discrete virulence systems [53]. Several authors have shown that LSPA-6 lineage II strains are less pathogenic, probably due to low Stx production [46,54,55]. Adherence to epithelial cells is higher for clade 8 strains than for clade 2 strains, although no differences have been observed in the invasiveness between the two clades. Strains belonging to clade 8 show upregulation of major virulence genes, including 29 of 41 LEE island genes, which are critical for adherence. The same has been observed for Stx coding genes and for virulence genes encoded in the plasmid, pO157 [56].
The stx2 gene is located on the λ family prophages immediately downstream of the phage late promoter (pR’). The expression of the stx2 gene is regulated by the transcription of the anti-terminator Q, which initiates the transcription at the late promoter pR’. It has been suggested that the anti-terminator q gene on the bacteriophage Q933 could be a useful marker of strains with high toxin production. In contrast, the q gene of bacteriophage 21 has been reported from E. coli O157:H7 with low Stx production [37,57,58].
STEC strains can colonize cattle for several months, and in this way, may serve as a gene reservoir and may be the origin of E. coli O157 genotypes with high virulence. Hence, the importance of characterizing genotypes that circulate in the livestock in a certain area, as the point of origin of strategies to reduce risks to human health [59]. Considering this, our group has previously carried out broad molecular characterization of the human and bovine O157 strains circulating in Argentina using different methodologies (PFGE, LSPA-6, SNP analysis, stx subtyping, and putative virulence factors and allele q detection, among others). Our data allows us to conclude that in contrast to the great genetic diversity observed in other studies worldwide, in Argentina, high homogeneity is observed in both cattle and human strains, with almost exclusive circulation of strains belonging to the hypervirulent clade 8 described by Manning et al. [51] also carrying also a significant set of putative virulence factors [60,61]. Other methods applied to STEC subtyping, like the Multiple-Locus Variable number tandem repeat Analysis (MLVA) and Multilocus Sequence Typing (MLST), were not used in our previous studies.
The aim of this review was to compare the genetic background of E. coli O157 strains isolated in countries that have conducted similar studies to try and correlate specific O157 genotypes with the incidence and severity of E. coli O157 associated diseases. This review focuses on E. coli O157:H7 (named throughout the manuscript as E. coli O157) because this serotype is the etiologic agent of more than 75% of HUS cases in Argentina.
A thorough web-based and PubMed search was conducted to identify relevant studies on these topics. We used the following search terms: Escherichia coli O157, Escherichia coli O157:H7, E. coli O157:H7, E. coli O157, STEC, EHEC, VTEC, Shiga toxin combined with LSPA-6 or clades or Q alleles or stx genotypes or Kulasekara factors or putative virulence factors.

2. Incidence of E. coli O157 Infections and HUS in Different Countries

Laboratory surveillance shows that the incidence of E. coli O157 infections varies widely from country to country, although these data may be biased. There has been considerable variation in sampling procedures and analysis of specimens, in the methodologies used, and in the epidemiological surveillance systems and records in each country [62]. In Argentina, data on human STEC infections are gathered through different strategies: (i) the reporting of clinical HUS cases to the National Health Surveillance System; these reports, which have been mandatory since 2000, must be immediate and individualized; (ii) the Sentinel Surveillance System through 25 HUS sentinel units; (iii) the laboratory-based surveillance system through the National Diarrheal and Foodborne Pathogens Network; and (iv) the Molecular Surveillance through the PulseNet of Latin America and Caribbean. Data on the incidence of E. coli O157 infections and HUS in different countries are shown in Table 1.
These data show that Argentina, which has the highest incidence of HUS in the world, has low incidence rates of E. coli O157 infections. In a previous study, we hypothesized that the strains circulating in this country have a high pathogenic potential to develop HUS, and the clinical evolution would be too fast to be detected at the first stage of diarrhea [76].

3. Genetic Features of the Isolates

A collection of 280 strains (226 non-related human and 54 cattle strains) of E. coli O157 from Argentina was analyzed by XbaI-PFGE, and a great diversity was found [61]. A total of 148 different patterns were detected. The five most common XbaI-PFGE patterns identified in both human and animal strains in this study had been included in the National Database. Two of these common patterns, AREXH01.0011 and AREXH01.0022, were predominant in the Argentine Database of E. coli O157 in the 1998–2008 period, representing 9.7% and 6.8% of samples, respectively. The AREXH01.0011 pattern is identical to the SMI-H and EXH01.0047 patterns, which are described as predominant in Sweden and the US, respectively [77].

3.1. LSPA-6 Analysis

Despite this remarkable diversity observed in PFGE studies, other molecular subtyping techniques applied to study population diversity showed a marked homogeneity of the strains circulating in Argentina. Thus, LSPA-6 showed that 98% of the Argentine strains belong to lineage I/II, which refers to 100% of clinical isolates and all except one strain of the bovine reservoir [61]. This differs from reports from other countries. Frequently, there is greater heterogeneity in the E. coli O157 lineages circulating, as well as considerable differences between bovine and human strains. Table 2 shows data from the Argentine strains studied by LSPA-6 compared with data from other countries analyzed with the same methodology.
The predominance of lineage I/II in Argentina is very high in both human and bovine strains. It is noteworthy that strains of lineage II, frequent in the bovine reservoir, were not detected in this collection of strains from Argentina [61]. A similar situation is that of Australia, although this country shows greater heterogeneity in the strains of the bovine reservoir, with a lower frequency of lineage I/II and detection of strains of lineage II that were absent in human strains. Scotland presents a similar situation with a broad predominance of strains of lineage I/II although the other two lineages are also detected in human strains. It is striking that in the bovine reservoir, 100% of the strains belong to lineage I/II. These three countries, in which lineage I/II predominates, present different rates of HUS. Argentina, with the highest incidence of HUS in the world also has the highest frequency of lineage I/II, to which the majority of the strains belong to. A country with a fairly similar situation with respect to LSPA-6 lineage is Australia, although this country has the lowest incidence rate of HUS. Scotland, which has an intermediate incidence rate of HUS, but one of the highest rates in Europe, shows a high prevalence of lineage I/II in human isolates. Belgium, with intermediate values of lineage I/II, is one of the European countries with intermediate incidence of HUS. Other countries, such as the USA, Japan and Canada, in which lineage I/II is not predominant, have lower incidences of HUS. There seems to be an association between the predominance of severe diseases and LSPA I/II lineage, although data from Australia could also indicate that lineage I/II includes strains with different levels of virulence and that in this country, unlike Argentina and Scotland, there are predominately strains with lower virulence in this lineage. A similar situation may be that of The Netherlands. Additional information can be derived from the analysis of data from The Netherlands. While in the bovine reservoir there is a broad predominance of strains of lineage II, they are rare in human cases. This could imply that strains of lineage II represent a lower risk for humans, probably due to a lower level of virulence.

3.2. Clade Analysis

In Argentina, an almost exclusive circulation of hypervirulent clade 8 strains is observed, and this could be related to the high incidence of HUS. The clade frequencies in bovine and human E. coli O157 strains from different countries are shown in Table 3 and Table 4, respectively.
Countries with intermediate values of clade 8, such as Sweden, also have intermediate rates of HUS. Australia has a very marked predominance of clade 7 strains and is a country with a low incidence of HUS. Something similar happens with Japan, although in this case, there is not such a marked predominance of this clade, and greater heterogeneity is observed in the distribution. Likewise, this country has low HUS rates. The US shows a predominance of isolates belonging to clade 2, although their intermediate HUS incidence could also be related to the intermediate frequency (24.1%) of clade 8 strains. One case to highlight is that of Scotland; although it has low percentages of clade 8 strains (6.8%), it has one of the highest HUS rates in Europe. This country shows a very broad predominance of strains belonging to clades 4/5, 6 or 7, without specifying the particular clade. Probably most of these strains do not belong to clade 7, which, as previously mentioned, includes low virulence strains. Some recent studies have shown a significant relationship between clade 6 strains and the most severe forms of E. coli O157 infections [87,88]; this could be the case for Scotland. This point deserves more research. As can be observed in the distribution of clades in bovine strains, especially in Argentina and Australia, the predominance of strains belonging to the same clades in bovine and human populations could demonstrate that most of these last strains have their origin in the bovine reservoir.

3.3. stx-Genotype Analysis

Argentina presents a clear predominance of stx2a/stx2c genotypes, which could be directly related to the high incidence of HUS. The distribution of stx-genotypes in bovine and human E. coli O157 isolated in different countries is shown in Table 4.
In countries with low or intermediate rates of HUS incidence, the stx2a/stx2c genotype is not the predominant one. In countries with a lower incidence of HUS, the stx2c variant predominates, in combination with stx1 (57.0–76.0%) or alone (4.0–30.0%), for example, in Australia. In Japan, the stx1/stx2a genotype clearly predominates (44.0–44.3%). This could confirm a decrease in the virulence of genotype stx2a when it is accompanied by stx1. This last piece of data seems to be ratified by the information from Belgium, since the clear predominance of genotype stx2a alone is related to one of the highest HUS rates in Europe. Again, it is observed that the predominance of specific genotypes in humans is related to their distributions in the bovine reservoir. An exception to this is the predominance of the stx2c genotype in cattle that is not observed in clinical strains, perhaps related to the lower virulence of this variant.

3.4. Anti-terminator Q Alleles Analysis

In relation to the anti-terminator Q, the simultaneous presence of the two q alleles is related to the higher incidence of HUS, as occurs in the case of Argentina. Table 5 shows the distribution of bovine and human q alleles in different countries.
The intermediate incidence of HUS is related to q933, which is broadly predominant in Belgium and is present in a similar percentage to q21 in The Netherlands. As in the cases analyzed above, the predominance of more virulent genotypes in human strains is linked to a similar predominance in the bovine reservoir. On the other hand, when less virulent forms prevail in cattle, this predominance is lost or diluted in human strains. This could indicate that the less virulent strains have low pathogenic capacity and therefore cause infections in humans less frequently.

3.5. Putative Virulence Determinants Analysis

In relation to the putative virulence factors described by Kulasekara et al. [52], the only one that shows an association with high incidences of HUS, such as in Argentina, is ECSP_3286. This factor is related to the extracellular transport of the heme complex. Table 6 shows the distribution of putative virulence factors of Kulasekara in human strains in different countries.
A similar relationship is observed, although to a lesser extent, with factor 2870/2872 which is related to adaptation in plant cells. A case that deserves further analysis is the ECSP_3620 factor, related to the intact gene that encodes a nitric oxide reductase (norV gene). The microorganisms carrying this intact gene have a longer survival time within macrophages since they markedly reduce the level of intracellular nitric oxide. It has also been shown that STEC carriers of this gene produce higher levels of Stx2 within the macrophages. These data could be related to a greater virulence of the E. coli O157 that carry this gene [95]. Despite this, the data in Table 6 show that the vast majority of strains are related to a high incidence rate of HUS (Argentina, 95.0–100% of the strains) as well as to lower incidence rates of the disease (Australia, 97.0% of the strains) involving the intact gene. As LSPA-6 lineage I/II predominates in both countries, despite their different incidences of HUS, it could be thought that the presence of ECSP_3620 is a characteristic of this lineage and is not related to the virulence of the strains. This hypothesis was considered in a recent paper by Shimizu et al. [96] where the norV gene was analyzed from the perspective of the evolution of E. coli O157.

4. Conclusions

The characteristics of the strains that cause disease in humans reflect the predominant genotypes in cattle in each of the countries analyzed. When LSPA-6 lineage II prevails widely in cattle, this predominance is markedly reduced in strains isolated from clinical cases; this is probably related to the low virulence of these strains. The LSPA-6 lineage I/II is related to the most severe cases of E. coli O157 infections. Despite this, data from Argentina and Australia show that it is not the only marker of the severity of infections. Clade 8 strains are clearly related to a higher incidence of HUS, although a similar relationship probably exists between strains belonging to clade 6 and serious diseases. The stx2a/stx2c genotype is linked to a high incidence of HUS and the stx2a genotype is linked to intermediate incidence. In addition, the stx1a gene predominates in strains isolated in countries with a low incidence of HUS. The simultaneous presence of the q933 and q21 alleles encoding the anti-terminator Q protein is associated with a high incidence of HUS, whereas the presence of q933 alone is linked to intermediate incidence. The only putative virulence factor described by Kulasekara that is related to the high incidence of HUS is EC_3286. The presence of the intact norV gene may not be related to virulence but could be a marker of LSPA-6 lineage I/II.

Author Contributions

L.P. and M.R. contributed equally to the design, writing and correction of the paper.

Acknowledgments

The authors thank Narelle Fegan from CSIRO Agriculture and Food, Werribee, Victoria, Australia, Denis Piérard from the Universitair Ziekenhuis Brussel, Brussels, Belgium, Erik Eriksson from Department of Microbiology, National Veterinary Institute, Uppsala, Sweden, and Camilla Sundborger from Public Health Agency of Sweden, for their contribution to this review with input data on human disease in their countries.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Centers for Disease Control. Isolation of E. coli O157:H7 from sporadic cases of hemorrhagic colitis—United States. MMWR Morb. Mortal. Wkly Rep. 1982, 31, 580–585. [Google Scholar]
  2. Griffin, P.M.; Tauxe, R.V. The epidemiology of infections caused by Escherichia coli O157:H7, other enterohemorrhagic E. coli, and the associated hemolytic syndrome. Epidemiol. Rev. 1991, 13, 60–98. [Google Scholar] [CrossRef] [PubMed]
  3. Gianantonio, C.; Vitacco, M.; Mendilaharzu, F.; Rutty, A.; Mendilaharzu, J. The hemolytic uremic syndrome. J. Pediatr. 1964, 64, 478–491. [Google Scholar] [CrossRef]
  4. Mele, C.; Remuzzi, G.; Noris, M. Hemolytic uremic síndrome. Semin. Immunopathol. 2014, 36, 399–420. [Google Scholar] [CrossRef] [PubMed]
  5. Walsh, P.R.; Johnson, S. Treatment and managment of children with haemolytic uraemic síndrome. Arch. Dis. Child. 2018, 103, 285–291. [Google Scholar] [PubMed]
  6. Mellmann, A.; Bielaszewska, M.; Köck, R.; Friedrich, A.W.; Fruth, A.; Middendorf, B.; Harmsen, D.; Schmidt, M.A.; Karch, H. Analysis of collection of Hemolytic Uremic Syndrome-associated Enterohemorragic Escherichia coli. Emerg. Infect. Dis. 2008, 14, 12871290. [Google Scholar] [CrossRef] [PubMed]
  7. Majowicz, S.E.; Scallan, E.; Jones-Bitton, A.; Sargeant, J.M.; Stapleton, J.; Angulo, F.J.; Yeung, D.H.; Kirk, M.D. Global incidence of human Shiga toxin-producing Escherichia coli infections and deaths: A systematic review and knowledge synthesis. Foodborne Pathog. Dis. 2014, 11, 447–455. [Google Scholar] [CrossRef] [PubMed]
  8. Pennington, H. Escherichia coli O157. Lancet 2010, 376, 1428–1435. [Google Scholar] [CrossRef]
  9. Innocent, G.T.; Mellor, D.J.; McEwen, S.A.; Reilly, W.J.; Smallwood, J.; Locking, M.E.; Shaw, D.J.; Michel, P.; Taylor, D.J.; Steele, W.B.; et al. Wellcome Trust-funded IPRAVE Consortium. Spatial and temporal epidemiology of sporadic human cases of Escherichia coli O157 in Scotland 1996–1999. Epidemiol. Infect. 2005, 133, 1033–1042. [Google Scholar] [CrossRef] [PubMed]
  10. Spizzirri, F.D.; Rahman, R.C.; Bibiloni, N.; Ruscasso, J.D.; Amoreo, O.R. Childhood hemolytic uremic syndrome in Argentina: Long term follow-up and prognostic features. Pediatr. Nephrol. 1997, 11, 156–160. [Google Scholar] [CrossRef] [PubMed]
  11. Boletín Integrado de Vigilancia N° 344–SE 3–Enero de 2017. Available online: http://www.msal.gob.ar/images/stories/boletines/Boletin-Integrado-De-Vigilancia-N344-SE3.pdf (accessed on 28 March 2018).
  12. Gyles, C.L. Shiga toxin-producing Escherichia coli: An overview. J. Anim. Sci. 2007, 85, E45–E62. [Google Scholar] [CrossRef] [PubMed]
  13. Milnes, A.S.; Stewart, I.; Clifton-Hadley, F.A.; Davies, R.H.; Newell, D.G.; Sayers, A.R.; Cheasty, T.; Cassar, C.; Ridley, A.; Cook, A.J.; et al. Intestinal carriage of verocytotoxigenic Escherichia coli O157, Salmonella, thermophilic Campylobacter and Yersinia enterocolitica in cattle, sheep and pigs at slaughter in Great Britain during 2003. Epidemiol. Infect. 2008, 136, 739–751. [Google Scholar] [CrossRef] [PubMed]
  14. Iowa State University Center for Food security and Public health. Enterohemorragic Escherichia coli and Other E. coli Causing Hemolytic Uremic Syndrome. Center for Food Security and Public Health Technical Factsheets.61. Available online: https://lib.dr.iastate.edu/cfsph_factsheets/61 (accessed on 17 April 2018).
  15. Tanaro, J.D.; Pianciola, L.A.; D’Astek, B.A.; Piaggio, M.C.; Mazzeo, M.L.; Zolezzi, G.; Rivas, M. Virulence profile of Escherichia coli O157 strains isolated from surface water in cattle breeding areas. Lett. Appl. Microbiol. 2018. [Google Scholar] [CrossRef] [PubMed]
  16. Snedeker, K.G.; Shaw, D.J.; Locking, M.E.; Prescott, R. Primary and secondary cases in Escherichia coli O157 outbreaks: A statistical analysis. BMC Infect. Dis. 2009, 9, 144. [Google Scholar] [CrossRef] [PubMed]
  17. Painter, J.A.; Hoekstra, R.M.; Ayers, T.; Tauxe, R.V.; Braden, C.R.; Angulo, F.J.; Griffin, P. Attribution of Foodborne Illnesses, Hospitalizations, and Deaths to Food Commodities by using Outbreak Data, United States, 1998–2008. Emerg. Infect. Dis. 2013, 19, 407–415. [Google Scholar] [CrossRef] [PubMed]
  18. Parry, S.M.; Salmon, R.L. Sporadic STEC O157 Infections: Secondary household transmission in Wales. Emerg. Infect. Dis. 1998, 4, 657–661. [Google Scholar] [CrossRef] [PubMed]
  19. Feng, P.; Lampel, K.A.; Karch, H.; Whittam, T.S. Genotypic and phenotypic changes in the emergence of Escherichia coli O157:H7. J. Infect. Dis. 1998, 177, 1750–1753. [Google Scholar] [CrossRef] [PubMed]
  20. Karch, H.; Bielaszewska, M. Sorbitol-fermenting Shiga toxin-producing Escherichia coli O157:H-strains: Epidemiology, phenotypic and molecular characteristics, and microbiological diagnosis. J. Clin. Microbiol. 2001, 39, 2043–2049. [Google Scholar] [CrossRef] [PubMed]
  21. Wick, L.M.; Qi, W.; Lacher, D.W.; Whittam, T.S. Evolution of genomic content in the stepwise emergence of Escherichia coli O157:H7. J. Bacteriol. 2005, 187, 1783–1791. [Google Scholar] [CrossRef] [PubMed]
  22. Leopold, S.R.; Magrini, V.; Holt, N.J.; Shaikh, N.; Mardis, E.R.; Cagno, J.; Ogura, Y.; Iguchi, A.; Hayashi, T.; Mellmann, A.; et al. A precise reconstruction of the emergence and constrained radiations of Escherichia coli O157 portrayed by backbone concatenomic analysis. PNAS 2009, 106, 8713–8718. [Google Scholar] [CrossRef] [PubMed]
  23. Hayashi, T.; Makino, K.; Ohnishi, M.; Kurokawa, K.; Ishii, K.; Yokoyama, K.; Han, C.G.; Ohtsubo, E.; Nakayama, K.; Murata, T.; et al. Complete Genome Sequence of Enterohemorrhagic Escherichia coli O157:H7 and Genomic Comparison with a Laboratory Strain K-12. DNA Res. 2001, 8, 11–22. [Google Scholar] [CrossRef] [PubMed]
  24. Perna, N.T.; Plunkett, G., 3rd; Burland, V.; Mau, B.; Glasner, J.D.; Rose, D.J.; Mayhew, G.F.; Evans, P.S.; Gregor, J.; Kirkpatrick, H.A.; et al. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 2001, 409, 529–533. [Google Scholar] [CrossRef] [PubMed]
  25. Dallman, T.J.; Byrne, L.; Ashton, P.M.; Cowley, L.A.; Perry, N.T.; Adak, G.; Petrovska, L.; Ellis, R.J.; Elson, R.; Underwood, A.; et al. Whole-Genome Sequencing for National Surveillance of Shiga Toxin–Producing Escherichia coli O157. Clin. Infect. Dis. 2015, 61, 305–312. [Google Scholar] [CrossRef] [PubMed]
  26. Karmali, M.A. Infection by Shiga toxin-producing Escherichia coli: An overview. Mol. Biotechnol. 2004, 26, 117–122. [Google Scholar] [CrossRef]
  27. Scheutz, F.; Teel, L.D.; Beutin, L.; Pierard, D.; Buvens, G.; Karch, H.; Mellmann, A.; Caprioli, A.; Tozzoli, R.; Morabito, S.; et al. A multi-center evaluation of a sequence-based protocol to subtype Shiga toxins and standardize Stx nomenclature. J. Clin. Microbiol. 2012, 50, 2951–2963. [Google Scholar] [CrossRef] [PubMed]
  28. Reiland, H.A.; Omolo, M.A.; Johnson, T.J.; Baumler, D.J. A Survey of Escherichia coli O157:H7 Virulence Factors: The First 25 Years and 13 Genomes. Adv. Microbiol. 2014, 4, 390–423. [Google Scholar] [CrossRef]
  29. Franz, E.; van Hoek, A.H.A.M.; van der Wal, F.J.; de Boer, A.; Zwartkruis-Nahuis, A.; van der Zwaluw, K.; Aarts, H.J.M.; Heuvelink, A.E. Genetic features differentiating bovine, food, and human isolates of Shiga toxin-producing Escherichia coli O157 in The Netherlands. J. Clin. Microbiol. 2012, 50, 772–780. [Google Scholar] [CrossRef] [PubMed]
  30. Withworth, J.H.; Fegan, N.; Keller, J.; Gobius, K.S.; Bono, J.L.; Call, D.R.; Hancock, D.D.; Besser, T.E. International comparison of clinical, bovine, and environmental Escherichia coli O157 isolates on the basis of Shiga toxin-encoding bacteriophage insertion site genotypes. Appl. Environ. Microbiol. 2008, 74, 7447–7450. [Google Scholar] [CrossRef] [PubMed]
  31. Islam, M.Z.; Musikiwa, A.; Islam, K.; Ahmed, S.; Chowdjury, S.; Ahad, A.; Biswas, P.K. Regional variation in the prevalence of E. coli O157 in cattle: A meta-analysis and meta-regression. PLoS ONE 2014, 9, e93299. [Google Scholar] [CrossRef] [PubMed]
  32. Chinen, I.; Otero, J.L.; Miliwebsky, E.S.; Rold, M.L.; Baschkier, A.; Chillemi, G.M.; Nóboli, C.; Frizzo, L.; Rivas, M. Isolation and characterisation of Shiga toxin-producing Escherichia coli O157:H7 from calves in Argentina. Res. Vet. Sci. 2003, 74, 283–286. [Google Scholar] [CrossRef]
  33. Fernandez, D.; Irino, K.; Sanz, M.E.; Padola, N.L.; Parma, A.E. Characterization of Shiga toxin-producing Escherichia coli isolated from dairy cows in Argentina. Lett. Appl. Microbiol. 2010, 51, 377–382. [Google Scholar] [CrossRef] [PubMed]
  34. Masana, M.O.; Leotta, G.A.; Castillo, L.L.D.; Dastek, B.A.; Palladino, P.M.; Galli, L.; Vilacoba, E.; Carbonari, C.; Rodríguez, H.R.; Rivas, M. Prevalence, characterization, and genotypic analysis of Escherichia coli O157:H7/NM from selected beef exporting abattoirs of Argentina. J. Food. Prot. 2010, 73, 649–656. [Google Scholar] [CrossRef] [PubMed]
  35. Meichtri, L.; Miliwebsky, E.; Gioffre, A.; Chinen, I.; Baschkier, A.; Chillemi, G.; Guth, B.E.; Masana, M.O.; Cataldi, A.; Rodríguez, H.R.; et al. Shiga toxin-producing Escherichia coli in healthy young beef steers from Argentina: Prevalence and virulence properties. Int. J. Food. Microbiol. 2004, 96, 189–198. [Google Scholar] [CrossRef] [PubMed]
  36. Tanaro, J.D.; Leotta, G.A.; Lound, L.H.; Galli, L.; Piaggio, M.C.; Carbonari, C.C.; Araujo, S.; Rivas, M. Escherichia coli O157 in bovine feces and surface water streams in a beef cattle farm of Argentina. Foodborne Pathog. Dis. 2010, 7, 475–477. [Google Scholar] [CrossRef] [PubMed]
  37. LeJeune, J.T.; Abedon, S.T.; Takemura, K.; Christie, N.P.; Sreevatsan, S. Human Escherichia coli O157:H7 genetic marker in isolates of bovine origin. Emerg. Infect. Dis. 2004, 10, 1482–1485. [Google Scholar] [CrossRef] [PubMed]
  38. Besser, T.E.; Shaikh, N.; Holt, N.J.; Tarr, P.I.; Konkel, M.E.; Malik-Kale, P.; Walsh, C.W.; Whittam, T.S.; Bono, J.L. Greater diversity of Shiga Toxin-encoding bacteriophage insertion sites among Escherichia coli O157:H7 isolates from cattle than in those from humans. Appl. Environ. Microbiol. 2007, 73, 671–679. [Google Scholar] [CrossRef] [PubMed]
  39. Jung, W.K.; Bono, J.L.; Clawson, M.L.; Leopold, S.R.; Shringi, S.; Besser, T.E. Lineage and genogroup-defining single nucleotide polymorphisms of Escherichia coli O157:H7. Appl. Environ. Microbiol. 2013, 79, 7036–7041. [Google Scholar] [CrossRef] [PubMed]
  40. Callaway, T.R.; Carr, M.A.; Edrington, T.S.; Anderson, R.C.; Nisbet, D.J. Diet, Escherichia coli O157:H7, and cattle: A review after 10 years. Curr. Issues Mol. Biol. 2009, 11, 67–80. [Google Scholar] [PubMed]
  41. Widgren, S.; Söderlund, R.; Eriksson, E.; Fasth, C.; Aspan, A.; Emanuelson, U.; Alenius, S.; Lindberg, A. Longitudinal observational study over 38 months of verotoxigenic Escherichia coli O157:H7 status in 126 cattle herds. Prev. Vet. Med. 2015, 121, 342–352. [Google Scholar] [CrossRef] [PubMed]
  42. Kudva, I.T.; Evans, P.S.; Perna, N.T.; Barrett, T.J.; Ausubel, F.M.; Blattner, F.R.; Calderwood, S.B. Strains of Escherichia coli O157:H7 differ primarily by insertions or deletions, not single-nucleotide polymorphisms. J. Bacteriol. 2002, 184, 1873–1879. [Google Scholar] [CrossRef] [PubMed]
  43. Shaikh, N.; Tarr, P.I. Escherichia coli O157:H7 Shiga toxin-encoding bacteriophages: Integrations, excisions, truncations, and evolutionary implications. J. Bacteriol. 2003, 185, 3596–3605. [Google Scholar] [CrossRef] [PubMed]
  44. Kim, J.; Nietfeldt, J.; Benson, A.K. Octamer-based genome scanning distinguishes a unique subpopulation of Escherichia coli O157:H7 strains in cattle. PNAS 1999, 96, 13288–13293. [Google Scholar] [CrossRef] [PubMed]
  45. Yang, Z.; Kovar, J.; Kim, J.; Nietfeldt, J.; Smith, D.; Moxley, R.A.; Olson, M.E.; Fey, P.D.; Benson, A.K. Identification of common subpopulations of non-sorbitol-fermenting, ß-glucuronidase-negative Escherichia coli O157:H7 from bovine production environments and human clinical samples. Appl. Environ. Microbiol. 2004, 70, 6846–6854. [Google Scholar] [CrossRef] [PubMed]
  46. Zhang, Y.; Laing, C.; Zhang, Z.; Hallewell, J.; You, C.; Ziebell, K.; Johnson, R.P.; Kropinski, A.M.; Thomas, J.E.; Karmali, M.; et al. Lineage and host source are both correlated with levels of Shiga toxin 2 production by Escherichia coli O157:H7 strains. Appl. Environ. Microbiol. 2010, 76, 474–482. [Google Scholar] [CrossRef] [PubMed]
  47. Elhadidy, M.; Elkhatib, W.F.; Abo Elfadl, E.A.; Verstraete, K.; Denayer, S.; Barbau-Piednoire, E.; De Zutter, L.; Verhaegen, B.; De Rauw, K.; Piérard, D.; et al. Genetic diversity of Shiga toxin-producing Escherichia coli O157:H7 recovered from human and food sources. Microbiology 2015, 161, 112–119. [Google Scholar] [CrossRef] [PubMed]
  48. Sharapov, U.M.; Wendel, A.M.; Davis, J.P.; Keene, W.E.; Farrar, J.; Sodha, S.; Hyytia-Trees, E.; Leeper, M.; Gerner-Smidt, P.; Griffin, P.M.; et al. Multistate outbreak of Escherichia coli O157:H7 infections associated with consumption of fresh spinach: United States, 2006. J. Food Prot. 2016, 79, 2024–2030. [Google Scholar] [CrossRef] [PubMed]
  49. Rangel, J.M.; Sparling, P.H.; Crowe, C.; Griffin, P.M.; Swerdlow, D.L. Epidemiology of Escherichia coli O157:H7 outbreaks, United States, 1982–2002. Emerg. Infect. Dis. 2005, 11, 603–609. [Google Scholar] [CrossRef] [PubMed]
  50. Fukushima, H.; Hashizume, T.; Morita, Y.; Tanaka, J.; Azuma, K.; Mizumoto, Y.; Kaneno, M.; Matsuura, M.; Konma, K.; Kitani, T. Clinical experiences in Sakai City Hospital during the massive outbreak of enterohemorrhagic Escherichia coli O157 infections in Sakai City, 1996. Pediatr. Int. 1999, 41, 213–217. [Google Scholar] [CrossRef] [PubMed]
  51. Manning, S.D.; Motiwala, A.S.; Springman, C.; Qi, W.; Lacher, D.W.; Ouellette, L.M.; Mladonicky, J.M.; Somsel, P.; Rudrik, J.T.; Dietrich, S.E.; et al. Variation in virulence among clades of Escherichia coli O157:H7 associated with disease outbreaks. PNAS 2008, 105, 4868–4873. [Google Scholar] [CrossRef] [PubMed]
  52. Kulasekara, B.R.; Jacobs, M.; Zhou, Y.; Wu, Z.; Sims, E.; Saenphimmachak, C.; Rohmer, L.; Ritchie, J.M.; Radey, M.; McKevitt, M.; et al. Analysis of the genome of the Escherichia coli O157:H7 2006 spinach-associated outbreak isolate indicates candidate genes that may enhance virulence. Infect. Immun. 2009, 77, 3713–3721. [Google Scholar] [CrossRef] [PubMed]
  53. Neupane, M.; Abu-Ali, G.S.; Mitra, A.; Lacher, D.W.; Manning, S.D. Shiga toxin 2 overexpression in Escherichia coli O157:H7 strains associated with severe human disease. Microb. Pathog. 2011, 51, 466–470. [Google Scholar] [CrossRef] [PubMed]
  54. Dowd, S.E.; Crippen, T.L.; Sun, Y.; Gontcharova, V.; Youn, E.; Muthaiyan, A.; Wolcott, R.D.; Callaway, T.R.; Ricke, S.C. Microarray analysis and draft genomes of two Escherichia coli O157:H7 lineage II cattle isolates FRIK966 and FRIK2000 investing lack of Shiga toxin expression. Foodborne Pathog. Dis. 2010, 7, 763–773. [Google Scholar] [CrossRef] [PubMed]
  55. Lowe, R.M.S.; Baines, D.; Selinger, L.B.; Thomas, J.E.; McAllister, T.A.; Sharma, R. Escherichia coli O157:H7 strain origin, lineage, and Shiga toxin 2 expression affect colonization of cattle. Appl. Environ. Microbiol. 2009, 75, 5074–5081. [Google Scholar] [CrossRef] [PubMed]
  56. Abu-Ali, G.S.; Ouellette, L.M.; Henderson, S.T.; Lacher, D.W.; Riordan, J.T.; Whittam, T.S.; Manning, S.D. Increased adherence and expression of virulence genes in a lineage of Escherichia coli O157:H7 commonly associated with human infections. PLoS ONE 2010, 5, e10167. [Google Scholar] [CrossRef] [PubMed]
  57. Ahmad, A.; Zurek, L. Evaluation of the anti-terminator Q933 gene as a marker for Escherichia coli O157:H7 with high Shiga toxin production. Curr. Microbiol. 2006, 53, 324–328. [Google Scholar] [CrossRef] [PubMed]
  58. Wagner, P.L.; Neely, M.N.; Zhang, X.; Acheson, D.W.K.; Waldor, M.K.; Friedman, D.I. Role for a phage promoter in Shiga toxin 2 expression from a pathogenic Escherichia coli strain. J. Bacteriol. 2001, 183, 2081–2085. [Google Scholar] [CrossRef] [PubMed]
  59. Barth, S.A.; Menge, C.; Eichhorn, I.; Semmler, T.; Wieler, L.H.; Pickard, D.; Belka, A.; Berens, C.; Geue, L. The accesory genome of Shiga toxin-producing Escherichia coli (STEC) defines a persistent colonization type in cattle. Appl. Environ. Microbiol. 2016, 82, 5455–5464. [Google Scholar] [CrossRef] [PubMed]
  60. Pianciola, L.; Chinen, I.; Mazzeo, M.; Miliwebsky, E.; González, G.; Müller, C.; Carbonari, C.; Navello, M.; Zitta, E.; Rivas, M. Genotypic characterization of Escherichia coli O157:H7 strains that cause diarrhea and hemolytic uremic syndrome in Neuquén, Argentina. Int. J. Med. Microbiol. 2014, 303, 499–504. [Google Scholar]
  61. Pianciola, L.; D’Astek, B.A.; Mazzeo, M.; Chinen, I.; Masana, M.; Rivas, M. Genetic features of human and bovine Escherichia coli O157:H7 strains isolated in Argentina. Int. J. Med. Microbiol. 2016, 306, 123–130. [Google Scholar] [CrossRef] [PubMed]
  62. O’Brien, S.J. VTEC: Risk factors and epidemiology in humans. In Proceedings of the Pathogenic E. coli Network Conference. Epidemiology and Transmission of VTEC and other Pathogenic Escherichia coli, Stockholm, Sweden, 25–26 September 2008; pp. 92–98. [Google Scholar]
  63. Mellor, G.E.; Sim, E.M.; Barlow, R.S.; D’Astek, B.A.; Galli, L.; Chinen, I.; Rivas, M.; Gobius, K.S. Phylogenetically related Argentinean and Australian Escherichia coli O157 isolates are distinguished by virulence clades and alternative Shiga toxin 1 and 2 prophages. Appl. Environ. Microbiol. 2012, 78, 4724–4731. [Google Scholar] [CrossRef] [PubMed]
  64. Vally, H.; Hall, G.; Dyda, A.; Raupach, J.; Knope, K.; Combs, B.; Desmarchelier, P. Epidemiology of Shiga toxin producing Escherichia coli in Australia. BMC Public Health 2012, 12, 63. [Google Scholar] [CrossRef] [PubMed]
  65. Rivas, M. Epidemiología del Síndrome Urémico Hemolítico en Argentina Situación Actual e Innovaciones Diagnósticas. Jornada de Síndrome Urémico Hemolítico Homenaje al Dr. Carlos A. Gianantonio. Buenos Aires, Argentina. 19 de Agosto de 2016. Available online: http://www.sap.org.ar/uploads/archivos/files_dra-rivas-epidemiologia-del-sindrome-uremico-hemolitico-en-argentina-situacion-actual-e-innovaciones-diagnosticas_1494446234.pdf (accessed on 21 March 2018).
  66. Centers for Disease Control and Prevention. National Enteric Disease Surveillance: Shiga Toxin-Producing Escherichia coli (STEC) Annual Report. 2015. Available online: https://www.cdc.gov/nationalsurveillance/’pdfs/STEC_Annual_Summary_2015-508c.pdf (accessed on 18 April 2018).
  67. Centers for Disease Control. Incidence and Trends of Infections with Pathogens Transmitted Commonly Through Food and the Effect of Increasing Use of Culture-Independent Diagnostic Tests on Surveillance —Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2013–2016. MMWR Morb. Mortal. Wkly Rep. 2017, 66, 397–403. [Google Scholar]
  68. National Institute of Infectious Diseases, Ministry of Health, Labour and Welfare, Japan. Pathogen Surveillance System in Japan and Infectious Agents Surveillance Report (IASR). Infect Agents Surveill Rep. Available online: https://nesid4g.mhlw.go.jp/Byogentai/Pdf/data77e.pdf (accessed on 21 March 2018).
  69. Kawasaki, Y.; Suyama, K.; Maeda, R.; Yugeta, E.; Takano, K.; Suzuki, S.; Sakuma, H.; Nemoto, K.; Sato, T.; Nagasawa, K.; et al. Incidence and index of severity of hemolytic uremic syndrome in a 26 year period in Fukushima Prefecture, Japan. Pediatr. Int. 2014, 56, 77–82. [Google Scholar] [CrossRef] [PubMed]
  70. Surveillance Atlas of Infectious Diseases. European Centre for Disease Prevention and Control. Available online: http://atlas.ecdc.europa.eu/public/index.aspx (accessed on 18 February 2018).
  71. BC Centre for Disease Control. E. coli (shigatoxigenic). Available online: http://www.bccdc.ca/resource-gallery/Documents/Statistics%20and%20Research/Statistics%20and%20Reports/Epid/Annual%20Reports/eColiShigatoxigenic.pdf (accessed on 28 March 2018).
  72. McLaine, P.N.; Rowe, P.C.; Orrbine, E. Experiences with HUS in Canada: What have we learned about childhood HUS in Canada? Kidney Int. 2009, 75, S25–S28. [Google Scholar] [CrossRef] [PubMed]
  73. Sundborger, C. Public Health Agency of Sweden. Personal communication, 2018. [Google Scholar]
  74. Laboratory of Microbiology and Infection Control, UZ Brussel. National Reference Centre for Shiga Toxin/Verotoxin-Producing Escherichia coli (NRC STEC/VTEC). Annual Report. 2016. Available online: https://nrchm.wiv-isp.be/nl/ref_centra_labo/shiga_toxine_verotoxine/Rapporten/Annual%20report%20NRC%20STEC%202016.pdf (accessed on 28 March 2018).
  75. Health Protection Scotland. STEC in Scotland 2016: Enhanced Surveillance and Reference Laboratory Data. 2017, 51. (32). Available online: http://www.hps.scot.nhs.uk/ewr/issuesearch.aspx (accessed on 18 February 2018).
  76. Pianciola, L.; Chinen, I.; Mazzeo, M.; Zolezzi, G.; González, G.; D’Astek, B.; Deza, N.; Navello, M.; Rivas, M. Hypervirulent Escherichia coli O157:H7 strains that cause hemolytic uremic syndrome in Neuquén, Argentina. In 8th International Symposium on Shiga Toxin (Verocytotoxin) Producing Escherichia coli Infections; VTEC: Amsterdam, The Netherlands, 2012; p. 130. [Google Scholar]
  77. Löfdahl, S. How global is VTEC? In Proceedings of the Pathogenic E. coli Network Conference. Epidemiology and Transmission of VTEC and other Pathogenic Escherichia coli, Stockholm, Sweden, 25–26 September 2008; pp. 65–67. [Google Scholar]
  78. Mellor, G.E.; Besser, T.E.; Davis, M.A.; Beavis, B.; Jung, W.; Smith, H.V.; Jennison, A.V.; Doyle, C.J.; Chandry, P.S.; Gobius, K.S.; et al. Multilocus genotype analysis of Escherichia coli O157 isolates from Australia and the United States provides evidence of geographic divergence. Appl. Environ. Microbiol. 2013, 79, 5050–5058. [Google Scholar] [CrossRef] [PubMed]
  79. Mellor, G.E.; Fegan, N.; Gobius, K.S.; Smith, H.V.; Jennison, A.V.; D’Astek, B.A.; Rivas, M.; Shringi, S.; Baker, K.N.K.; Besser, T.E. Geographically distinct Escherichia coli O157 differ by lineage, Shiga toxin genotype and total Shiga toxin production. J. Clin. Microbiol. 2015, 53, 579–586. [Google Scholar] [CrossRef] [PubMed]
  80. Hartzell, A.; Chen, C.; Lewis, C.; Liu, K.; Reynolds, S.; Dudley, E.G. Escherichia coli O157:H7 of genotype Lineage-Specific Polymorphism Assay 211111 and clade 8 are common clinical isolates within Pennsylvania. Foodborne Pathog. Dis. 2011, 8, 763–768. [Google Scholar] [CrossRef] [PubMed]
  81. Laing, C.; Pegg, C.; Yawney, D.; Ziebell, K.; Steele, M.; Johnson, R.; Thomas, J.E.; Taboada, E.N.; Zhang, Y.; Gannon, V.P.J. Rapid determination of Escherichia coli O157:H7 lineage types and molecular subtypes by using comparative genomic fingerprinting. Appl. Environ. Microbiol. 2008, 74, 6606–6615. [Google Scholar] [CrossRef] [PubMed]
  82. Sharma, R.; Standford, K.; Louie, M.; Munns, K.; John, S.J.; Zhang, Y.; Gannon, V.; Chui, L.; Read, R.; Topp, E.; et al. Escherichia coli O157:H7 lineages in health beef and dairy cattle and clinical human cases in Alberta, Canada. J. Food Protect. 2009, 72, 601–607. [Google Scholar] [CrossRef]
  83. Strachan, N.J.; Rotariu, O.; Lopes, B.; MacRae, M.; Fairley, S.; Laing, C.; Gannon, V.; Allison, L.J.; Hanson, M.F.; Dallman, T.; et al. Whole genome sequencing demonstrates that geographic variation of Escherichia coli O157 genotypes dominates host association. Sci. Rep. 2015, 5, 14145. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  84. Yokoyama, E.; Hirai, S.; Hashimoto, R.; Uchimura, M. Clade analysis of enterohemorragic Escherichia coli serotype O157H7/H-strains and hierarchy of their phylogenetic relationships. Infect. Genet. Evol. 2012, 12, 1724–1728. [Google Scholar] [CrossRef] [PubMed]
  85. Hirai, S.; Yokoyama, E.; Etoh, Y.; Seto, J.; Ichihara, S.; Suzuki, Y.; Maeda, E.; Sera, N.; Horikawa, K.; Yamamoto, T. Analysis of the population genetics of clades of enterohaemorrhagic Escherichia coli O157:H7/H-isolated in three areas in Japan. J. Appl. Microbiol. 2014, 117, 1191–1197. [Google Scholar] [CrossRef] [PubMed]
  86. Elhadidy, M.M.; Elkhatib, W.F. Multilocus genotypic characterization of Escherichia coli O157:H7 recovered from food sources. Epidemiol. Infect. 2015, 143, 2367–2372. [Google Scholar] [CrossRef] [PubMed]
  87. Iyoda, S.; Manning, S.D.; Seto, K.; Kimata, K.; Isobe, J.; Etoh, Y.; Ichihara, S.; Migita, Y.; Ogata, K.; Honda, M.; et al. Phylogenetic clades 6 and 8 of enterohemorragic Escherichia coli O157:H7 with particular stx sybtypes are more frequently found in isolates from Hemolytic Uremic Syndrome patients than from asymptomatic carriers. Open Forum Infect. Dis. 2014, 1, ofu061. [Google Scholar] [CrossRef] [PubMed]
  88. Amigo, N.; Mercado, E.; Bentancor, A.; Singh, P.; Vilte, D.; Gerhardt, E.; Zotta, E.; Ibarra, C.; Manning, S.D.; Larzábal, M.; et al. Clade 8 and clade 6 strains of Escherichia coli O157:H7 from cattle in Argentina have hypervirulent-like phenotypes. PLoS ONE 2015, 10, e0127710. [Google Scholar] [CrossRef] [PubMed]
  89. Eriksson, E.; Soderlund, R.; Bovqvist, S.; Aspan, A. Genotypic characterization to identify markers associated with putative hypervirulence in Swedish Escherichia coli O157:H7 cattle strains. J. Appl. Microbiol. 2010, 110, 323–332. [Google Scholar] [CrossRef] [PubMed]
  90. Ogura, Y.; Mondal, S.I.; Islam, M.R.; Mako, T.; Arisawa, K.; Katsura, K.; Ooka, T.; Gotoh, Y.; Murase, K.; Ohnishi, M.; et al. The shiga toxin 2 production level in enterohemorragic Escherichia coli O157:H7 is correlated with the subtypes of toxin-encoding phage. Sci. Rep. 2015, 5, 16663. [Google Scholar] [CrossRef] [PubMed]
  91. Aspán, A.; Eriksson, E. Verotoxigenic Escherichia coli O157:H7 from Swedish cattle; isolates from prevalence studies versus strains linked to human infections. A retrospective study. BMC Vet. Res. 2010, 6, 7. [Google Scholar] [CrossRef] [PubMed]
  92. Kawano, K.; Ono, H.; Iwashita, O.; Kurogi, M.; Haga, T.; Maeda, K.; Goto, Y. Stx genotype and molecular epidemiological analyses of Shiga toxin-producing Eschercihia coli O157:H7/H- in human and cattle isolates. Eur. J. Clin. Microbiol. Infect. Dis. 2012, 31, 119–127. [Google Scholar] [CrossRef] [PubMed]
  93. Buvens, G.; De Gheldre, Y.; Dediste, A.; de Moreau, A.I.; Mascart, G.; Simon, A.; Allemeersch, D.; Scheutz, F.; Lauwers, S.; Piérard, D. Incidence and Virulence Determinants of Verocytotoxin-Producing Escherichia coli Infections in the Brussels-Capital Region, Belgium, in 2008–2010. J. Clin. Microbiol. 2012, 50, 1336–1345. [Google Scholar] [CrossRef] [PubMed]
  94. Matsumoto, M.; Suzuki, M.; Takahashi, M.; Hirose, K.; Minagawa, H.; Ohta, M. Identification and epidemiological description of enterohemorragic Escherichia coli O157 strains producing low amounts of Shiga toxin 2 in Aichi Prefecture, Japan. Jpn. J. Infect. Dis. 2008, 61, 442–445. [Google Scholar] [PubMed]
  95. Shimizu, T.; Tsutsuki, H.; Matsumoto, A.; Nakaya, H.; Noda, M. The nitric oxide reductase of enterohemorrhagic Escherichia coli plays an important role for the survival within macrophages. Mol. Microbiol. 2012, 85, 492–512. [Google Scholar] [CrossRef] [PubMed]
  96. Shimizu, T.; Hirai, S.; Yokoyama, E.; Ichimura, K.; Noda, M. An evolutionary analysis of nitric oxid reductase gene norV in enterohemorragic Escherichia coli O157. Infect. Genet. Evol. 2015, 33, 176–181. [Google Scholar] [CrossRef] [PubMed]
Table
Table 1. Incidence of E. coli O157 infections per 100,000 inhabitants and HUS per 100,000 children under 5 years of age.
Table 1. Incidence of E. coli O157 infections per 100,000 inhabitants and HUS per 100,000 children under 5 years of age.
CountryE. coli O157 InfectionsHUSReferences
Australia0.230.49[63,64]
Argentina0.428.8[11,65]
US0.971.18[66,67]
Japan0.710.88/10⁵ < 15 years *[68,69]
The Netherlands0.460.80[70]
Canada0.84 1.04[71,72]
Sweden0.641.19[70,73]
Belgium0.364.5[70,74]
Scotland3.43.4[75]
* No data available for individuals <5 years of age.
Table
Table 2. Values (or interval of values from different sources) of lineage-specific polymorphism assay-6 (LSPA-6) lineage frequency in (a) bovine, and (b) human E. coli O157 strains from different countries.
Table 2. Values (or interval of values from different sources) of lineage-specific polymorphism assay-6 (LSPA-6) lineage frequency in (a) bovine, and (b) human E. coli O157 strains from different countries.
(a)
Bovine
CountryLSPA-LILSPA-LI/IILSPA-LIIReferences
Australia1.0–3.081.0–85.012.0–18.0[63,78,79]
Argentina0–7.093.0–1000[61,63,79]
US45.0–63.017.0–31.03.0–38.0[78,80]
The Netherlands1.435.663.0[29]
Canada49.5–75.51.5–4.720.4–45.8[81,82]
Scotland01000[83]
No data available for Japan, Sweden and Belgium.
(b)
Human
CountryLSPA-LILSPA-LI/IILSPA-LIIReferences
Australia4.0–5.095.0–96.00[63,78,79]
Argentina0–4.096.0–1000[61,63,79]
US72.012.0–14.014.0–16.0[78,79]
Japan51.1–58.530.7–34.410.5–14.5[84,85]
The Netherlands14.177.68.2[29]
Canada72.8–92.04.0–13.64.0–15.0[81,82]
Belgium10.977.211.9[86]
Scotland1.491.96.7[83]
No data available for Sweden.
Table
Table 3. Values (or interval of values from different sources) of clade frequency in (a) bovine and (b) human E. coli O157 strains from different countries.
Table 3. Values (or interval of values from different sources) of clade frequency in (a) bovine and (b) human E. coli O157 strains from different countries.
(a)
CountryBovine Clades (%)References
1234/5678
Australia002023.074.02.0[63]
Argentina000–8.033.3–42.00050.0–59.3[62,63]
The NetherlandsNDNDNDNDNDND41.1[29]
Sweden00066.70033.3[89]
ScotlandNDNDND96.23.8[83]
ND: no data available for US, Japan, Canada and Belgium.
(b)
CountryHuman Clades (%)References
1234/5678Other
Australia02.0006.092.000[63]
Argentina000–3.07.2–16.00081.0–91.40[60,61,63]
US0.547.49.75.23.25.724.14.2[51]
Japan1.5–3.49.2–22.916.8–34.00–1.73.9–5.216.5–53.86.7–12.80–12.8[84,85,87,90]
The NetherlandsNDNDNDNDNDND38.8ND[29]
Sweden01.08.024.012.017.037.01.0[91]
ScotlandNDND1.491.86.8ND[83]
No data available for Canada and Belgium.
Table
Table 4. Values (or interval of values from different sources) of stx-genotype frequencies in (a) bovine E. coli O157 strains isolated in different countries.
Table 4. Values (or interval of values from different sources) of stx-genotype frequencies in (a) bovine E. coli O157 strains isolated in different countries.
(a)
CountryBovine stx Genotypes (%)References
11/2a1/2a/2c1/2c2a2a/2c2c
Australia0–2.01.0–4.0060.0–71.00–0.50–3.025.0–36.1[63,78,79]
Argentina0–7.04.0–7.47.4–10.01.9–13.09.3–12.033.0–55.516.6–20.0[61,63,79]
US2.1–4.044.0–60.00–1.46.7–21.04.0–13.70–11.16.7–23.8[78,79,80]
Japan0–7.029.9–30.00–0.97.0–19.79.0–12.00–6.830.7–47.0[88,90,91,92]
Sweden0–1.40039.1–46.70–2.730.4–40.013.3–26.4[86,87,89,90,91]
No data available for The Netherlands, Canada, Belgium and Scotland.
(b)
CountryHuman stx Genotypes (%)References
11/2a1/2a/2c1/2c2a2a/2c2c
Australia7.6–10.03.0–8.0057.0–76.00–1.30–4.04.0–30.0[63,78,79]
Argentina0–4.002.2–10.00–8.016.0–20.853.0–76.10.9–8.0[61,63,79]
US0–2.860.0–63.70–1.15.0–8.017.3–24.04.0–4.54.0–5.0[78,79]
Japan0–0.644.0–44.30–1.54.0–4.913.0–16.24.0–11.021.5–35.0[87,92]
Belgium0–3.00–5.90–2.90–35.320.6–44.48.8–26.026.5–27.0[47,93]
No data available for The Netherlands, Canada, Sweden and Scotland.
Table
Table 5. Values (or range of values from different sources) of q allele frequencies in (a) bovine and (b) human E. coli O157 strains isolated from different countries.
Table 5. Values (or range of values from different sources) of q allele frequencies in (a) bovine and (b) human E. coli O157 strains isolated from different countries.
(a)
CountryBovine q Alleles (%)References
q21q933q21 + q933None
Australia100000[37]
Argentina24.116.759.20[61]
US54.044.02.00[37]
Japan82.018.000[37]
The Netherlands84.99.61.44.1[29]
Scotland25.0075.00[37]
No data available for Canada, Sweden and Belgium.
(b)
CountryHuman q Alleles (%)References
q21q933q21 + q933None
Argentina1.8–2.915.981.2–81.30[60,61]
Japan19.474.66.00[94]
The Netherlands38.834.123.53.5[29]
Belgium20.061.019.00[47]
No data available for Australia, US, Canada, Sweden and Scotland.
Table
Table 6. Values (or range of values from different sources) of putative virulence factors frequency in human E. coli O157 strains isolated in different countries.
Table 6. Values (or range of values from different sources) of putative virulence factors frequency in human E. coli O157 strains isolated in different countries.
CountryPutative Virulence Factors * in Human Strains (%)References
0242177326872870/287232863620
Australia92.023.090.040.02.097.0[78]
Argentina93.0–10021.0–33.577.0–82.763.0–85.760.0–88.695–100[1,60,78]
US35.08.031.028.027.042.0[52]
No data available for Japan, The Netherlands, Canada, Sweden, Belgium and Scotland. * Putative virulence factors: 0242 is linked to protein–protein interactions, 1773 encodes a protein that interferes with the immune response, 2687 encodes a protein that reduces the expression of cytokines, 2870/2872 is related to adaptation to plant hosts, 3286 encodes a protein that binds to heme, 3620 encodes anaerobic nitric oxidase.

Share and Cite

MDPI and ACS Style

Pianciola, L.; Rivas, M. Genotypic Features of Clinical and Bovine Escherichia coli O157 Strains Isolated in Countries with Different Associated-Disease Incidences. Microorganisms 2018, 6, 36. https://doi.org/10.3390/microorganisms6020036

AMA Style

Pianciola L, Rivas M. Genotypic Features of Clinical and Bovine Escherichia coli O157 Strains Isolated in Countries with Different Associated-Disease Incidences. Microorganisms. 2018; 6(2):36. https://doi.org/10.3390/microorganisms6020036

Chicago/Turabian Style

Pianciola, Luis, and Marta Rivas. 2018. "Genotypic Features of Clinical and Bovine Escherichia coli O157 Strains Isolated in Countries with Different Associated-Disease Incidences" Microorganisms 6, no. 2: 36. https://doi.org/10.3390/microorganisms6020036

APA Style

Pianciola, L., & Rivas, M. (2018). Genotypic Features of Clinical and Bovine Escherichia coli O157 Strains Isolated in Countries with Different Associated-Disease Incidences. Microorganisms, 6(2), 36. https://doi.org/10.3390/microorganisms6020036

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop