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Review

An Overview on Streptococcus bovis/Streptococcus equinus Complex Isolates: Identification to the Species/Subspecies Level and Antibiotic Resistance

by
Arianna Pompilio
1,2,
Giovanni Di Bonaventura
1,2 and
Giovanni Gherardi
3,*
1
Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara, Via Luigi Polacchi 11, 66100 Chieti, Italy
2
Center of Excellence on Aging and Translational Medicine, “G. d’Annunzio” University of Chieti-Pescara, Via Luigi Polacchi 11, 66100 Chieti, Italy
3
Department of Medicine, Campus Biomedico University, Via Alvaro del Portillo 200, 00128 Rome, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 480; https://doi.org/10.3390/ijms20030480
Submission received: 20 December 2018 / Revised: 14 January 2019 / Accepted: 20 January 2019 / Published: 23 January 2019
(This article belongs to the Special Issue Drug Resistance: Mechanisms and New Strategies)
Versions Notes

Abstract

:
Streptococcus bovis/Streptococcus equinus complex (SBSEC), a non-enterococcal group D Streptococcus spp. complex, has been described as commensal bacteria in humans and animals, with a fecal carriage rate in humans varying from 5% to over 60%. Among streptococci, SBSEC isolates represent the most antibiotic-resistant species—with variable resistance rates reported for clindamycin, erythromycin, tetracycline, and levofloxacin—and might act as a reservoir of multiple acquired genes. Moreover, reduced susceptibility to penicillin and vancomycin associated with mobile genetic elements have also been detected, although rarely. Since the association of SBSEC bacteremia and colon lesions, infective endocarditis and hepatobiliary diseases has been established, particularly in elderly individuals, an accurate identification of SBSEC isolates to the species and subspecies level, as well as the evaluation of antibiotic resistance, are needed. In this paper, we reviewed the major methods used to identify SBSEC isolates and the antimicrobial resistance rates reported in the scientific literature among SBSEC species.

1. Introduction

Streptococcus bovis/Streptococcus equinus complex (SBSEC), a non-enterococcal group D Streptococcus spp. complex, comprises several species: Streptococcus equinus, Streptococcus infantarius subsp. infantarius, Streptococcus lutetiensis, Streptococcus alactolyticus and three subspecies of the clade Streptococcus gallolyticus, namely S. gallolyticus subsp. gallolyticus (SGSG), S. gallolyticus subsp. macedonicus and S. gallolyticus subsp. pasteurianus (SGSP). SBSEC consists of commensal bacteria, mainly described as colonizers of the rumen, crop, and cloaca of animals and colon of humans, with a fecal carriage rate of SBSEC member in humans ranging from 5% to over 60% [1]. Some SBSEC have been found to cause serious infections such as bacteremia and infective endocarditis in humans, particularly in southern Europe, with the prevalence rising both in animal and elderly patients [2,3,4,5]. The traditional association of SBSEC bacteremia with colorectal cancer was first described in the late 1970s [6] and later extensively confirmed in the literature [7,8,9]. Moreover, an association between S. bovis isolation and chronic liver and biliary tract disorders has also been described [10]. Unfortunately, it is still unclear how commensal-to-pathogens transition occurs in SBSEC members, particularly relating to survival, colonization, adhesion, invasion, and interaction with the host immune system. Likewise, the knowledge on the virulence and pathogenicity of SBSEC is limited only to a few adhesion molecules and pro-inflammatory factors [1]. Moreover, members of the SBSEC have also been increasingly identified as important species in the food preparations such as those encountered in food fermentations where they contribute to the quality of the fermented food product [11]. Some SBSEC strains, such as S. gallolyticus subsp. macedonicus and S. lutetiensis, are ingested as part of the daily diet and therefore might be considered to be safe, thus rendering this bacterial group unique among streptococci, containing both pathogenic and “good” strains [1,11].
The difficulties encountered over the years in the correct identification of SBSEC to the species and subspecies level by phenotypic and genotypic methods, made a harmonized analysis of the literature difficult to achieve [12]. This situation is further complicated by the lack of an optimal molecular method for the correct identification to the species level. Moreover, the current classification system remains subject to debate and is not uniformly accepted due to the absence of a curated sequencing database, the lack of revised nomenclature in culture collection deposits, and the imperfect updates to commercial phenotypic identification database systems. The introduction of the new nomenclature of SBSEC species and subspecies revealed specific diseases associations among the different species. SGSG represents the major cause of infective endocarditis and monomicrobial bacteremia, associated with colorectal cancer [13,14,15]. In particular, SGSG has been demonstrated to carry unique virulence factors facilitating both the infection through premalignant colonic lesions and the innate immune system evasion, and the formation of biofilm at collagen-rich sites in susceptible patients with colorectal cancer [14]. SGSP and S. infantarius seem, instead, mainly related to immunosuppressive comorbidities and polymicrobial bacteremia, while being associated with biliary-pancreatic diseases and biliary tract infections. S. infantarius is most frequently associated with bile duct and biliary-pancreatic cancers, whereas SGSP is associated with benign biliary tract diseases [16,17] and, at lesser extent, to urinary tract infections, osteoarticular infections, gastrointestinal infections, and meningitis, mostly in elderly patients [18,19,20,21,22,23]. Geographic differences in epidemiology and prevalence occur among SBSEC species: SGSG is the most frequent species causing infective endocarditis in Europe, whereas SGSP seems to be more prevalent in Asia [24].
Among streptococci, SBSEC isolates represent the most antibiotic-resistant species, with variable resistance rates observed for clindamycin, erythromycin, tetracycline and levofloxacin [11]. Even though penicillin-resistant isolates have still not been observed, reduced susceptibility to penicillin has been rarely reported [25]; moreover, vancomycin resistance genes being carried on mobile genetic elements due to horizontal gene transfer from commensal fecal microbiota have also been detected, although rarely.
The present narrative review is focused on the major diagnostic methods used to identify SBSEC isolates, as well as on the antimicrobial resistance rates reported among SBSEC species.

2. Diagnostic Methods for the Identification of SBSEC

To retrieve published works on diagnostic methods for SBSEC identification, we searched PubMed electronic database for all eligible studies focused on identification of S. bovis and/or S. gallolyticus isolates published since 2000, as well as the more cited papers. The search was restricted to all papers that clearly reported data on identification of isolates belonging to SBSEC and those in the English language only. The results of diagnostic methods reported for the identification of SBSEC are summarized in Table 1.
The identity of SBSEC strains in human diseases has not been systematically investigated using modern taxonomy. Considering the specific association between diseases and microbiology features, accurate identification of SBSEC isolates is mandatory. The massive changes in the SBSEC taxonomy have resulted in confusing use of SBSEC species’ names in the scientific literature due to many studies published before the recommended current taxonomy, and to the evidence that the current taxonomy has not been completely adopted.
Traditionally, SBSEC has been classified into the non-enterococcal group D Lancefield antigen Streptococcus, and the identification to the bacterial species was initially performed by phenotypic tests [26]. In the early 1960s, the development of classification systems placed S. bovis into a more defined scheme among the Group D streptococci. The main biochemical differences between group D enterococci and S. bovis were based on the ability to grow in 6.5% NaCl, hydrolyze arginine, and decarboxylate tyrosine [27]. Due to the increased importance of SBSEC isolates in human infections, Facklam emphasized the importance of an accurate speciation by phenotypic methods to understand the species distribution of group D streptococci among human infections, as well as antimicrobial susceptibilities [28]. Based on phenotypic/biochemical tests, SBSEC species were grouped into 2 biotypes: biotype I (mannitol-fermenting) and biotype II (mannitol-nonfermenting). Biotype II was subdivided into II/1 and II/2, based on trehalose fermentation, β-galactosidase and β-glucuronidase activities, and starch degradation [17,28,29]. Phenotypic biochemical methods have been the most common species identification methodologies used in routine diagnostic laboratories in recent years, though they have limited differentiation capacity due to the phenotypic variability [30,31,32,33,34,35,36]. Moreover, they are time-consuming techniques providing species identification only after 24–48 h. For full biochemical and phenotypic descriptions, we invite to refer to Bergey’s Manual and their implementations in API and VITEK identification approaches [37].
Using the scheme proposed by Schlegel et al. [12] based on DNA studies, SBSEC taxonomy significantly changed, and later significantly improved using methodologies based on DNA-DNA hybridization, and single-gene-based molecular testing (i.e., 16S rRNA, groEL, and sodA). This allowed us to reclassify SBSEC into 7 different (sub)species grouped into four clusters, with two Streptococcus species of principal interest in human pathogenesis: S. gallolyticus - with the subspecies SGSG, formerly biotype I, and SGSP, formerly biotype II/2 - and S. infantarius, formerly biotype II/1, with the subspecies coli and infantarius [12,17,38,39]. Partial sequence comparison of rpoB, sodA, groEL, and gyrB within the genus Streptococcus indicated that these genes are more discriminative than 16S rRNA gene sequence, and partial groEL gene sequence comparison generally represents the best tool for the identification at species and subspecies levels [40].
Besides the phenotypic-based approaches, diagnostic methods used for identification of SBSEC also include proteomic-based MALDI-TOF (Matrix Assisted Laser Desorption Ionization Time-of-Flight analysis), and genomic-based methods, such as single-gene-based molecular testing (16S rRNA, sodA, groEL, and other genes), 65 and the recently introduced whole genome sequencing. Multilocus sequence typing has also been successfully applied to identify and discriminate species of the SBSEC [5,41,42]. It has been clearly demonstrated that no single test system among phenotypic, molecular or proteomic methods can provide unequivocal identification, whereas a combination of these techniques is often used to achieve the best performance for the accurate identification of SBSEC to the species level.
Several molecular methods have been developed to improve species identification of streptococci, included SBSEC, such as PCR and sequencing of 16S rRNA, rnpB, groEL, and sodA, with different outcomes [22,43,44].
Partial or complete nucleotide sequences of 16S rRNA amplicons have been found to be useful for SBSEC identification [16,45]. It has been reported that the detection of four different point mutations in 16S rRNA could be essential to discriminate among SGSG, SGSP and S. infantarius subsp. coli [39]. We recently found that 16S rRNA gene sequencing successfully clusters SGSG and SGSP into two separated and well-defined groups with the use of the phylogenetic tree provided by a curated website [46]. A study on 172 bacteremic S. bovis complex isolates - comprising SGSG, SGSP and S. infantarius—confirmed subspecies identification by sequencing of both 16S rRNA and sodA genes and by PCR-RFLP (Restriction-Fragment-Length-Polymorphism) assays of groESL gene [43]. PCR-RFLP assay based on groESL sequences combined with Vitek2 was also used to study 24 bacteremic cases with SBSEC infections, encompassing 13 SGSP, six SGSG, four S. infantarius subsp. coli, and one S. infantarius subsp. infantarius [47]. A multiplex PCR assay comprising the 16S rRNA gene followed by RFLP has been successfully applied on 200 SBSEC isolates from dairy products and reference strains, thus representing another molecular method developed to improve species identification of SBSEC able to discriminate Streptococcus infantarius (biotype II.1) from Streptococcus gallolyticus (biotype I and II.2)/Streptococcus alactolyticus and S. equinus [48]. In several cases, partial sodA gene sequencing was more discriminant than the 16S rRNA [33,36,49,50]. Moreover, partial sequencing of ribosomal protein S2 gene, rpsB, was successfully applied to cluster SGSG and SGSP isolates responsible for cases of meningitis in adults [21].
Real-time PCR assays based on the recN and gyrB genes have been developed to reliably detect from rectal swab specimens SBSEC subspecies, namely SGSG, SGSP, Streptococcus infantarius subsp. coli, and S. infantarius [51]. Moreover, DNA sequencing of the 16S–23S intergenic spacer (ITS) region has also been used to retrospectively identify SBSEC isolates recovered from blood cultures [23]. Recently the use of amplification and sequencing of tanB for SGSG, and of the SGPB0680 cell wall surface protein gene for SGSP was demonstrated to be accurate in the identification of six clinically relevant streptococcal species, including SBSEC isolates [52].
Recently, the MALDI-TOF MS (Mass-Spectrometry) technique has gained considerable interest in many microbiology laboratories where it is currently the main method for species identification. It is a very fast and cheap methodology showing similar and, in some cases, better performance than 16S rRNA gene sequencing [53,54]. Nevertheless, in some cases, the accuracy of the MALDI-TOF methodology is limited to the identification of a specific bacterial complex or group, as it is also used for some streptococcal species, including those of SBSEC. A limitation of MALDI-TOF Bruker in discriminating SBSEC species has been reported with variable performance and high dependence on the system, spectral databases and algorithms used [19]. Recently, the comparative evaluation of two MALDI-TOF systems, Bruker Biotyper and Vitek MS, considering 16S rRNA and 16S-23S intergenic spacer region sequencing as the reference method, revealed several inaccuracies, therefore suggesting the need for additional optimization of the available system databases or identification algorithms [55]. Conversely, other works reported the usefulness of MALDI-TOF to identify streptococcal species correctly. Hinse et al. demonstrated a good SBSEC species- and subspecies-level of discrimination based on dendrogram analysis of mass spectral profiles using the SARAMIS database (bioMérieux Italia, Florence, Italy) with MALDI-TOF MS instrument (Shimadzu Corp., Kyoto, Japan), using sodA gene sequencing as the reference method [56]. Similarly, another study that also used sodA gene sequencing as the gold standard method confirmed the usefulness of MALDI-TOF Bruker technology to properly discriminate between SGSG and SGSP, with some problems encountered with S. equinus species [57]. Moreover, another report on a collection of 54 and 97 streptococcal type strains and clinical isolates, respectively, including SBSEC species, revealed both MALDI Biotyper (Bruker Daltonics Italia, Macerata, Italy) and VITEK-MS (bioMérieux) to be reliable and accurate in clinical diagnostics for streptococcal identification compared with 16S rRNA gene sequencing as the reference method, providing better results than commercial biochemical methods [58]. Another comparative study on the identification of bacteremic streptococcal species, comprising SBSEC and based on rnpB gene sequencing and 2 MALDI-TOF systems, MALDI Biotyper (Bruker) and VITEK MS IVD (bioMérieux), showed excellent and comparable performances of the three methods [44]. Finally, in a recent study, we confirmed the usefulness of MALDI Biotyper (Bruker) and Vitek MS (bioMérieux) systems to identify SGSP isolates to the species level correctly, although only Bruker Biotyper accurately identified strains to the subspecies level [46].

3. Antimicrobial Resistance

The widespread use of antibiotics caused a relevant selective environmental pressure, selecting antibiotic-resistant bacterial species and favoring their spread. This selection reflects the increasing presence of antibiotic-resistant commensal bacteria in the gut microbiota of both humans and animals that might act as a reservoir of antibiotic resistance genes with the potential of being transmitted to pathogens through genomic exchange. Among them, enterococci are the most abundant genus found in the human gastrointestinal tract [59], but streptococci are also represented, mainly by SBSEC isolates.
In this narrative review, we included all papers published since 2000 that reported resistance rates among SBSEC isolates. Papers in languages other than English, review articles, papers that included a small number (less than 15) of SBSEC isolates, and those where the number of isolates or antibiotic resistance rates was not clearly reported, were all excluded from this analysis.
Based on these criteria 16 articles were overall retrieved, and the results of antibiotic resistance rates are summarized in Table 2. Overall, tetracycline, erythromycin, and clindamycin were the antimicrobial agents showing the highest resistance rates, ranging between 36% and 77% for tetracycline, 8.9% and 78% for erythromycin, and between 10.6% and 62% for clindamycin. The most recent study retrieved was from Italy and performed on SGSP isolates collected between 2010 and 2012: 31.8% were erythromycin-resistant and positive for erm(B) resistance gene, whereas all of them were also clindamycin-resistant [46]. Moreover, 68.2% of SGSP strains were tetracycline-resistant, most of those carrying tet(O), whereas a minority harbored the tet(M) gene [46]. A previous study from Italy was conducted on 25 S. bovis isolates responsible for endocarditis or bacteremia during 1990–2003 and classified as SGSG (20 isolates), SGSP (4 isolates), and S. infantarius (SI, 1 isolate). All isolates were susceptible to penicillin, glycopeptides, and linezolid, whereas 4%, 48%, 8%, and 64% of isolates were resistant to levofloxacin, erythromycin, gentamicin, and tetracycline, respectively [60]. Among 45 S. bovis isolates causing bacteremia recovered from 2003 to 2010 in Spain and re-identified according to the new taxonomic scheme, all isolates remained susceptible to penicillin, ampicillin, amoxicillin-clavulanate, oxacillin, quinupristin-dalfopristin, linezolid, and rifampin, whereas resistance rates of 33.3%, 15.6%, and 20.2% were reported, respectively for erythromycin, levofloxacin, and co-trimoxazole [19]. Variable resistance rates according to the bacterial species were reported and S. lutetiensis showed the highest resistance rates for erythromycin and clindamycin (60% for both) [19]. Lower erythromycin resistance rates (less than 20%) were reported in two separate studies. Among 45 independent carriage S. bovis isolates from Israel, approximately 9% of isolates were erythromycin-resistant [61]. In Japan, all 66 S. gallolyticus isolates recovered from various sources in both humans and animals between 1981 and 2011 were susceptible to vancomycin, penicillin G, and ampicillin. Low resistance rates were found for erythromycin, clindamycin, cefotaxime, and chloramphenicol (16.7%, 10.6%, 15.2%, and 4.5%, respectively) with the majority of erythromycin-resistant isolates harboring erm(B) gene [62]. Higher resistance rates were observed for tetracyclines (56.6% and 68.2%, respectively for tetracycline and doxycycline), with all tetracycline-resistant isolates showing either tet(M), tet(O), or tet(L) [62].
Erythromycin resistance rates higher than 40% were found in other studies. Assessing the activity of daptomycin against bacteremic streptococci from an international collection including 100 S. bovis isolates, Streit et al. [63] found that all S. bovis isolates were susceptible to vancomycin, daptomycin, and linezolid, whereas 97% and 94% were susceptible respectively to penicillin and quinupristin/dalfopristin; resistance rates for erythromycin, clindamycin, and tetracycline were of 46%, 26%, and 65%, respectively. In Hong Kong, China, among 48 SBSEC bacteremic isolates (mainly SGSP) collected over the period 1996–2001, an erythromycin resistance rate of 65% was found, mostly associated with erm(B) and erm(T), and a clindamycin resistance rate of 41% [24]. Another study from China, investigating clinical and microbiological features of 23 episodes of peritoneal dialysis peritonitis caused by S. bovis, reported resistance rates to clindamycin and erythromycin of 43.5% and 47.8%, respectively, [64]. A recent study from Taiwan, among 172 SBSEC collected between 2000 and 2012—including SGSG (126 isolates), SGSP (31 isolates), and S. infantarius (15 isolates)—54.7% of isolates were erythromycin-resistant, mostly showing the iMLSB phenotype (inducible resistance to macrolide, lincosamide, and streptogramin B antibiotics), thus with concomitant resistance also to clindamycin (54.1%) [43]. S. infantarius was the most frequent SBSEC species associated with multidrug-resistance [43]. In another previous study from Taiwan performed on 60 SBSEC blood isolates, mostly SGSP, collected between 1996 and 2000, a total of 63.3% of erythromycin-resistant strains were identified associated with the resistance genes erm(B) or erm(T) [65].
Leclercq et al. reported 59.4% of macrolide resistance rate in 128 clinical SBSEC isolates, mainly belonging to SGSG, with the vast majority harboring the resistance gene erm(B) [66]. Overall, 77.7% of isolates were tetracycline-resistant associated with tet(M), tet(L), and/or tet(O) [66]. Several studies from Spain conducted on SBSEC and complying the criteria used in the present review reported variable antibiotic resistance rates for erythromycin (48-78%) and clindamycin (45–72%). Matesanz et al. studying 118 SBSEC isolates, mostly SGSP, causing bacteriuria in adult patients and recovered during the period 2003–2012, reported that all isolates were susceptible to penicillin, whereas 48% and 45% of strains were resistant to erythromycin and clindamycin, respectively [20]. In a study on 41 SBSEC isolates from animals and humans collected between 1990 and 2010, 46.3% of isolates were erythromycin-resistant all but one carrying erm(B), 48.8% were clindamycin-resistant, and 36.6% were minocycline-resistant isolates all harboring tet(M) [67]. Indeed, 5 isolates were gentamycin-resistant with aac(6’)-aph(2’) gene, 6 (14.6%) were quinupristin-dalfopristin resistant, 5 (12.2%) were levofloxacin-resistant, and 3 (7.3%) were cotrimoxazole-resistant [67]. Another study from Spain conducted among 107 consecutive cases of bacteremia with or without infective endocarditis caused by SBSEC, prevalently SGSG, over two periods (1988–1996 and 1997–2005), reported that all isolates were penicillin-susceptible, whereas resistance rates for erythromycin, clindamycin, and cotrimoxazole were 60.2%, 54.5%, and 85.3%, respectively [68]. In a previous prospective study focused on 64 isolates belonging to SBSEC species and causing significant bacteremia in adult patients during the period 1987–2003, the totality of the isolates was susceptible to penicillin, cefotaxime, and vancomycin, whereas 60%, 60%, and 50% were resistant to erythromycin, trimethoprim/sulfamethoxazole, or clindamycin, respectively [69]. Finally, in another in vitro study aimed at evaluating the susceptibility profiles of 18 S. bovis bloodborne isolates collected between 1998 and 2003, 11% of isolates showed reduced susceptibility to penicillin whereas 78%, 72%, and 39% were resistant to erythromycin, clindamycin, or telithromycin, respectively [25]. All but one erythromycin-resistant isolate carried erm(B), whereas the remaining isolate carried mef(A) [25].
Regarding the mechanisms underlying the macrolide resistance, erm(B) has been identified as the most frequent erythromycin-resistant determinant, followed by erm(T) and mef(A) [24,25,46,62,65,66,67]. Moreover, erm(T) gene—identified flanking the mobile element IS1216V—has also been described in 6 inducible erythromycin-resistant SGSP isolates [70]. Recently, 6 SGSP isolates from dead ducklings collected in China during 2010–2013 were found to exhibit multi-drug resistance, including high macrolide resistance and carried erm(B) and erm(T) genes, clustering with Tn916 and IS1216, respectively [71]. Tetracycline resistance has been described to be mainly associated with tet(M), followed by tet(O). Moreover, a recent molecular characterization of 39 foodborne tetracycline-resistant isolates of S. bovis identified a novel mosaic tet(S/M) fusion [72]. Indeed, a new mechanism has been recently identified associated with macrolide resistance: two previously unknown conjugative transposons, Tn6263 and Tn6331, were found to confer aminoglycoside/macrolide co-resistance identified in a clinical isolate of SGSG responsible for infective endocarditis and colorectal cancer [73].
Several works reported reduced susceptibility to penicillin among SBSEC bacterial species. Although very low rates of reduced susceptibility to penicillin have been reported in some studies, ranging between 0.6% to 3% [43,63], other papers reported higher rates of low levels of penicillin-resistance (Table 2). Thirty percent of isolates from China causing peritoneal dialysis peritonitis showed moderate resistance to penicillin [64]. Reduced susceptibility to penicillin (MIC: 0.75 mg/L) was also reported in a clinical isolate of S. bovis biotype II/2 (SGSP) causing neonatal meningitis [74]. Among carriage S. bovis isolates from Israel, approximately 13% of isolates were penicillin-resistant [61]. Similarly, a reduced susceptibility to penicillin among S. bovis isolates with a rate of 11% has been reported by Rodrıguez-Avial et al. [25] (Table 2).
Vancomycin resistance has been rarely reported in SBSEC isolates from animal fecal samples and has been mainly associated with vanB gene carried on transferable elements. The finding of a vancomycin-resistant strain from a stool swab in human is of concern [67,75,76,77]. Comparative genomic analyses revealed that such a strain underwent extensive genetic elements exchange and chromosomal rearrangements with the acquisition of an unusually high number of transposable elements [67] (Table 2). With regard to the other antimicrobial agents, it is worthwhile to mention the high resistance rates for trimethoprim-sulfamethoxazole reported in some studies, varying from 7% to 98% [19,20,67,68,69].

4. Conclusions

The identification to the species level of SBSEC is mandatory because of the specific disease association reported in the literature. The combination of proteomic and molecular methods allows the correct and precise identification of SBSEC to the species level, and the simultaneous application of multiple identification methods along with the clinical presentation of the patient seems to be essential. However, whole genome studies will be useful in the future to improve the accuracy of identification and for identifying specific virulence factors associated with specific diseases.
SBSEC isolates, along with other gut Firmicutes such as enterococci and eubacteria, are resident of the gastrointestinal tract and may represent potential reservoirs for horizontal gene transfer of virulence factors and antibiotic resistance genes among the mammalian gastrointestinal microbiota. This, added to the evidence that antibiotic resistance is widespread among the SBSEC clinical isolates, representing a serious problem due to the increasing infection rates, makes necessary the continuous monitoring of resistance profiles in SBSEC isolates.

Author Contributions

Conception and methodology of the work, writing—review & editing, A.P., G.D.B. and G.G.

Acknowledgments

This research was funded by the “G. d’Annunzio” University of Chieti-Pescara, grant “fondi FAR; anno 2018”. The authors warmly thank Sherry Lynn Jones (Department of Education and Training; International Critical Incident Stress Foundation; Ellicott City, MD, USA) for reviewing the manuscript for the English language.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Jans, C.; Boleij, A. The Road to Infection: Host-Microbe Interactions Defining the Pathogenicity of Streptococcus bovis/Streptococcus equinus Complex Members. Front. Microbiol. 2018, 9, 603. [Google Scholar] [CrossRef]
  2. Durante-Mangoni, E.; Bradley, S.; Selton-Suty, C.; Tripodi, M.F.; Barsic, B.; Bouza, E.; Cabell, C.H.; Ramos, A.I.; Fowler, V., Jr.; Hoen, B.; et al. Current features of infective endocarditis in elderly patients: Results of the International Collaboration on Endocarditis Prospective Cohort Study. Arch. Intern. Med. 2008, 168, 2095–2103. [Google Scholar] [CrossRef] [PubMed]
  3. Chow, J.; Tang, H.; Mazmanian, S.K. Pathobionts of the Gastrointestinal Microbiota and Inflammatory Disease. Curr. Opin. Immunol. 2011, 23, 473–480. [Google Scholar] [CrossRef]
  4. Boleij, A.; Tjalsma, H. The itinerary of Streptococcus gallolyticus Infection in Patients with Colonic Malignant Disease. Lancet Infect. Dis. 2013, 13, 719–724. [Google Scholar] [CrossRef]
  5. Jans, C.; de Wouters, T.; Bonfoh, B.; Lacroix, C.; Kaindi, D.W.M.; Anderegg, J.; Böck, D.; Vitali, S.; Schmid, T.; Isenring, J.; et al. Phylogenetic, Epidemiological and Functional Analyses of the Streptococcus bovis/Streptococcus equinus Complex through an Overarching MLST Scheme. BMC Microbiol. 2016, 16, 117. [Google Scholar] [CrossRef] [PubMed]
  6. Klein, R.S.; Recco, R.A.; Catalano, M.T.; Edberg, S.C.; Casey, J.I.; Steigbigel, N.H. Association of Streptococcus bovis with Carcinoma of the Colon. N. Engl. J. Med. 1977, 297, 800–802. [Google Scholar] [CrossRef]
  7. Burnett-Hartman, A.N.; Newcomb, P.A.; Potter, J.D. Infectious Agents and Colorectal Cancer: A Review of Helicobacter pylori, Streptococcus bovis, JC virus and Human Papillomavirus. Cancer Epidemiol. Biomarkers Prev. 2008, 17, 2970–2979. [Google Scholar] [CrossRef] [PubMed]
  8. Gupta, A.; Madani, R.; Mukhtar, H. Streptococcus bovis Endocarditis; a Silent Sign for Colonic Tumour. Colorectal Dis. 2010, 12, 164–171. [Google Scholar] [CrossRef] [PubMed]
  9. Dahmus, J.D.; Kotler, D.L.; Kastenberg, D.M.; Kistler, C.A. The Gut Microbiome and Colorectal Cancer: A Review of Bacterial Pathogenesis. J. Gastrointest. Oncol. 2018, 9, 769–777. [Google Scholar] [CrossRef]
  10. Gonzalez-Quintela, A.; Martínez-Rey, C.; Castroagudín, J.F.; Rajo-Iglesias, M.C.; Domínguez-Santalla, M.J. Prevalence of Liver Disease in Patients with Streptococcus bovis Bacteraemia. J. Infect. 2001, 42, 116–119. [Google Scholar] [CrossRef]
  11. Jans, C.; Meile, L.; Lacroix, C.; Stevens, M.J. Genomics, Evolution, and Molecular Epidemiology of the Streptococcus bovis/Streptococcus equinus Complex (SBSEC). Infect. Genet. Evol. 2015, 33, 419–436. [Google Scholar] [CrossRef] [PubMed]
  12. Schlegel, L.; Grimont, F.; Ageron, E.; Grimont, P.A.D.; Bouvet, A. Reappraisal of the Taxonomy of the Streptococcus bovis/Streptococcus equinus Complex and Related Species: Description of Streptococcus gallolyticus subsp. gallolyticus subsp. nov., S. gallolyticus subsp. macedonicus subsp. nov. and S. gallolyticus subsp. pasteurianus subsp. nov. Int. J. Syst. Evol. Microbiol. 2003, 53, 631–645. [Google Scholar]
  13. Vaska, V.L.; Faoagali, J.L. Streptococcus bovis Bacteraemia: Identification within Organism Complex and Association with Endocarditis and Colonic Malignancy. Pathology 2009, 41, 183–186. [Google Scholar] [CrossRef] [PubMed]
  14. Boleij, A.; Muytjens, C.M.; Bukhari, S.I.; Cayet, N.; Glaser, P.; Hermans, P.W.; Swinkels, D.W.; Bolhuis, A.; Tjalsma, H. Novel Clues on the Specific Association of Streptococcus gallolyticus subsp. gallolyticus with Colorectal Cancer. J. Infect. Dis. 2011, 203, 1101–1109. [Google Scholar] [CrossRef]
  15. Boleij, A.; van Gelder, M.M.; Swinkels, D.W.; Tjalsma, H. Clinical Importance of Streptococcus gallolyticus Infection among Colorectal Cancer Patients: Systematic Review and Meta-Analysis. Clin. Infect. Dis. 2011, 53, 870–878. [Google Scholar] [CrossRef]
  16. Corredoira, J.; Alonso, M.P.; García-Garrote, F.; García-Pais, M.J.; Coira, A.; Rabuñal, R.; Gonzalez-Ramirez, A.; Pita, J.; Matesanz, M.; Velasco, D.; et al. Streptococcus bovis Group and Biliary Tract Infections: An Analysis of 51 Cases. Clin. Microbiol. Infect. 2014, 20, 405–409. [Google Scholar] [CrossRef]
  17. Dekker, J.P.; Lau, A.F. An Update on the Streptococcus bovis Group: Classification, Identification, and Disease Associations. J. Clin. Microbiol. 2016, 54, 1694–1699. [Google Scholar] [CrossRef]
  18. Fernandez-Ruiz, M.; Villar-Silva, J.; Llenas-Garcia, J.; Caurcel-Diaz, L.; Vila-Santos, J.; Sanz-Sanz, F.; Chaves, F.; Guerra-Vales, J.M. Streptococcus bovis Bacteraemia Revisited: Clinical and Microbiological Correlates in a Contemporary Series of 59 Patients. J. Infect. 2010, 61, 307–313. [Google Scholar] [CrossRef] [PubMed]
  19. Romero, B.; Morosini, M.I.; Loza, E.; Rodríguez-Baños, M.; Navas, E.; Cantón, R.; Campo, R.D. Reidentification of Streptococcus bovis Isolates Causing Bacteremia According to the New Taxonomy Criteria: Still an Issue? J. Clin. Microbiol. 2011, 49, 3228–3233. [Google Scholar] [CrossRef]
  20. Matesanz, M.; Rubal, D.; Iñiguez, I.; Rabuñal, R.; García-Garrote, F.; Coira, A.; García-País, M.J.; Pita, J.; Rodriguez-Macias, A.; López-Álvarez, M.J.; et al. Is Streptococcus bovis a Urinary Pathogen? Eur. J. Clin. Microbiol. Infect Dis. 2015, 34, 719–725. [Google Scholar] [CrossRef] [PubMed]
  21. van Samkar, A.; Brouwer, M.C.; Pannekoek, Y.; van der Ende, A.; van de Beek, D. Streptococcus gallolyticus Meningitis in Adults: Report of Five Cases and Review of the Literature. Clin. Microbiol. Infect. 2015, 21, 1077–1083. [Google Scholar] [CrossRef]
  22. García-País, M.J.; Rabuñal, R.; Armesto, V.; López-Reboiro, M.; García-Garrote, F.; Coira, A.; Pita, J.; Rodríguez-Macías, A.I.; López-Álvarez, M.J.; Alonso, M.P.; et al. Streptococcus bovis Septic Arthritis and Osteomyelitis: A Report of 21 Cases and a Literature Review. Semin. Arthritis Rheum. 2016, 45, 738–746. [Google Scholar] [CrossRef] [PubMed]
  23. Marmolin, E.S.; Hartmeyer, G.N.; Christensen, J.J.; Nielsen, X.C.; Dargis, R.; Skov, M.N.; Knudsen, E.; Kemp, M.; Justesen, U.S. Bacteremia with the bovis Group Streptococci: Species Identification and Association with Infective Endocarditis and with Gastrointestinal Disease. Diagn. Microbiol. Infect. Dis. 2016, 85, 239–242. [Google Scholar] [CrossRef]
  24. Lee, R.A.; Woo, P.C.Y.; To, A.P.C.; Lau, S.K.P.; Wong, S.S.Y.; Yuen, K.Y. Geographical Difference of Disease Association in Streptococcus bovis Bacteraemia. J. Med. Microbiol. 2003, 52, 903–908. [Google Scholar] [CrossRef] [PubMed]
  25. Rodriguez-Avial, I.; Rodriguez-Avial, C.; Culebras, E.; Picazo, J.J. In vitro Activity of Telithromycin Against viridans Group Streptococci and Streptococcus bovis Isolated from Blood: Antimicrobial Susceptibility Patterns in Different Groups of Species. Antimicrob. Agents Chemother. 2005, 49, 820–823. [Google Scholar] [CrossRef] [PubMed]
  26. Sherman, J.M. The Enterococci and Related Streptococci. J. Bacteriol. 1938, 35, 81–93. [Google Scholar]
  27. Deibel, R.H. The Group D Streptococci. Bacteriol. Rev. 1964, 28, 330–366. [Google Scholar]
  28. Facklam, R. What happened to the streptococci: Overview of taxonomic and nomenclature changes. Clin. Microbiol. Rev. 2002, 15, 613–630. [Google Scholar] [CrossRef]
  29. Ruoff, K.L.; Miller, S.I.; Garner, C.V.; Ferraro, M.J.; Calderwood, S.B. Bacteremia with Streptococcus bovis and Streptococcus salivarius: Clinical Correlates of More Accurate Identification of Isolates. J. Clin. Microbiol. 1989, 27, 305–308. [Google Scholar]
  30. Tardif, G.; Sulavik, M.C.; Jones, G.W.; Clewell, D.B. Spontaneous Switching of the Sucrose Promoted Colony Phenotype in Streptococcus sanguis. Infect. Immun. 1989, 57, 3945–3948. [Google Scholar]
  31. Beighton, D.; Hardie, J.M.; Whiley, R.A. A Scheme for the Identification of viridans Streptococci. J. Med. Microbiol. 1991, 35, 367–372. [Google Scholar] [CrossRef]
  32. Kikuchi, K.; Enari, T.; Totsuka, K.; Shimizu, K. Comparison of Phenotypic Characteristics, DNA-DNA Hybridization Results, and Results with a Commercial Rapid Biochemical and Enzymatic Reaction System for Identification of viridans Group Streptococci. J. Clin. Microbiol. 1995, 33, 1215–1222. [Google Scholar]
  33. Hoshino, T.; Fujiwara, T.; Kilian, M. Use of Phylogenetic and Phenotypic Analyses to Identify Nonhemolytic Streptococci Isolated from Bacteremic Patients. J. Clin. Microbiol. 2005, 43, 6073–6085. [Google Scholar] [CrossRef] [PubMed]
  34. Innings, A.; Krabbe, M.; Ullberg, M.; Herrmann, B. Identification of 43 Streptococcus Species by Pyrosequencing Analysis of the rnpB Gene. J. Clin. Microbiol. 2005, 43, 5983–5991. [Google Scholar] [CrossRef]
  35. Doern, C.D.; Burnham, C.A.D. It’s not Easy Being Green: The viridans Group Streptococci, with a focus on Pediatric Clinical Manifestations. J. Clin. Microbiol. 2010, 48, 3829–3835. [Google Scholar] [CrossRef] [PubMed]
  36. Teles, C.; Smith, A.; Ramage, G.; Lang, S. Identification of Clinically Relevant viridans Group Streptococci by Phenotypic and Genotypic Analysis. Eur. J. Clin. Microbiol. Infect. Dis. 2011, 30, 243–250. [Google Scholar] [CrossRef] [PubMed]
  37. Whiley, R.A.; Hardie, J.M. Genus, I. Streptococcus. In Bergey’s Manual of Systematic Bacteriology: The Firmicutes, 2nd ed.; De Vos, P., Garrity, G.M., Jones, D., Krieg, N.R., Ludwig, W., Rainey, F.A., Schleifer, K.H., Whitman, W.B., Eds.; Springer: New York, NY, USA, 2009; pp. 655–711. [Google Scholar]
  38. Poyart, C.; Quesne, G.; Trieu-Cuot, P. Taxonomic Dissection of the Streptococcus bovis Group by Analysis of Manganese-Dependent Superoxide Dismutase Gene (sodA) Sequences: Reclassification of ‘Streptococcus infantarius subsp. coli’ as Streptococcus lutetiensis sp. nov. and of Streptococcus bovis Biotype II.2 as Streptococcus pasteurianus sp. nov. Int. J. Syst. Evol. Microbiol. 2002, 52, 1247–1255. [Google Scholar]
  39. Beck, M.; Frodl, R.; Funke, G. Comprehensive Study of Strains Previously Designated Streptococcus bovis Consecutively Isolated from Human Blood Cultures and Emended Description of Streptococcus gallolyticus and Streptococcus infantarius subsp. coli. J. Clin. Microbiol. 2008, 46, 2966–2972. [Google Scholar] [CrossRef] [PubMed]
  40. Glazunova, O.O.; Raoult, D.; Roux, V. Partial Sequence Comparison of the rpoB, sodA, groEL and gyrB Genes Within the Genus Streptococcus. Int. J. Syst. Evol. Microbiol. 2009, 59, 2317–2322. [Google Scholar] [CrossRef]
  41. Dumke, J.; Hinse, D.; Vollmer, T.; Knabbe, C.; Dreier, J. Development and Application of a Multilocus Sequence Typing Scheme for Streptococcus gallolyticus subsp. gallolyticus. J. Clin. Microbiol. 2014, 52, 2472–2478. [Google Scholar] [CrossRef] [PubMed]
  42. Shibata, Y.; Tien Le, H.T.; Nomoto, R.; Osawa, R. Development of a Multilocus Sequence Typing Scheme for Streptococcus gallolyticus. Microbiology 2014, 160, 113–122. [Google Scholar] [CrossRef]
  43. Sheng, W.H.; Chuang, Y.C.; Teng, L.J.; Hsueh, P.R. Bacteraemia Due to Streptococcus gallolyticus subspecies pasteurianus is Associated with Digestive tract Malignancies and Resistance to Macrolides and Clindamycin. J. Infect. 2014, 69, 145–153. [Google Scholar] [CrossRef]
  44. Isaksson, J.; Rasmussen, M.; Nilson, B.; Stadler, L.S.; Kurland, S.; Olaison, L.; Ek, E.; Herrmann, B. Comparison of Species Identification of endocarditis Associated viridans Streptococci Using rnpB Genotyping and 2 MALDI-TOF Systems. Diagn. Microbiol. Infect. Dis. 2015, 81, 240–245. [Google Scholar] [CrossRef] [PubMed]
  45. Ben-Chetrit, E.; Wiener-Well, Y.; Kashat, L.; Yinnon, A.M.; Assous, M.V. Streptococcus bovis New Taxonomy: Does Subspecies Distinction Matter? Eur. J. Clin. Microbiol. Infect. Dis. 2017, 36, 387–393. [Google Scholar] [CrossRef] [PubMed]
  46. Gherardi, G.; Palmieri, C.; Marini, E.; Pompilio, A.; Crocetta, V.; Di Bonaventura, G.; Creti, R.; Facinelli, B. Identification, Antimicrobial Resistance and Molecular Characterization of the Human Emerging Pathogen Streptococcus gallolyticus subsp. pasteurianus. Diagn. Microbiol. Infect. Dis. 2016, 86, 329–335. [Google Scholar] [CrossRef]
  47. Lazarovitch, T.; Shango, M.; Levine, M.; Brusovansky, R.; Akins, R.; Hayakawa, K.; Lephart, P.R.; Sobel, J.D.; Kaye, K.S.; Marchaim, D. The Relationship between the New Taxonomy of Streptococcus bovis and Its Clonality to Colon Cancer, Endocarditis, and Biliary Disease. Infection 2013, 41, 329–337. [Google Scholar] [CrossRef]
  48. Jans, C.; Lacroix, C.; Meile, L. A Novel Multiplex PCR/RFLP Assay for the Identification of Streptococcus bovis/Streptococcus equinus Complex Members from Dairy Microbial Communities Based on the 16S rRNA Gene. FEMS Microbiol. Lett. 2012, 326, 144–150. [Google Scholar] [CrossRef]
  49. Poyart, C.; Quesne, G.; Coulon, S.; Berche, P.; Trieu-Cuot, P. Identification of Streptococci to Species Level by Sequencing the Gene Encoding the Manganese-Dependent Superoxide Dismutase. J. Clin. Microbiol. 1998, 36, 41–47. [Google Scholar]
  50. Sasaki, E.; Osawa, R.; Nishitani, Y.; Whiley, R.A. Development of a Diagnostic PCR Assay Targeting the Mn-Dependent Superoxide Dismutase Gene (sodA) for Identification of Streptococcus gallolyticus. J. Clin. Microbiol. 2004, 42, 1360–1362. [Google Scholar] [CrossRef]
  51. Lopes, P.G.; Cantarelli, V.V.; Agnes, G.; Costabeber, A.M.; d’Azevedo, P.A. Novel Real-time PCR Assays Using TaqMan Minor Groove Binder Probes for Identification of Fecal Carriage of Streptococcus bovis/Streptococcus equinus Complex from Rectal Swab Specimens. J. Clin. Microbiol. 2014, 52, 974–976. [Google Scholar] [CrossRef] [PubMed]
  52. Hatrongjit, R.; Akeda, Y.; Hamada, S.; Gottschalk, M.; Kerdsin, A. Multiplex PCR for Identification of Six Clinically Relevant Streptococci. J. Med. Microbiol. 2017, 66, 1590–1595. [Google Scholar] [CrossRef] [PubMed]
  53. Seng, P.; Rolain, J.M.; Fournier, P.E.; La Scola, B.; Drancourt, M.; Raoult, D. MALDI-TOF-Mass Spectrometry Applications in Clinical Microbiology. Future Microbiol. 2010, 5, 1733–1754. [Google Scholar] [CrossRef]
  54. Wieser, A.; Schneider, L.; Jung, J.; Schubert, S. MALDI-TOF MS in Microbiological Diagnostics-Identification of Microorganisms and Beyond. Appl. Microbiol. Biotechnol. 2012, 93, 965–974. [Google Scholar] [CrossRef] [PubMed]
  55. Agergaard, C.N.; Knudsen, E.; Dargis, R.; Nielsen, X.C.; Christensen, J.J.; Justesen, U.S. Species Identification of Streptococcus bovis Group Isolates Causing Bacteremia: A Comparison of Two MALDI-TOF MS Systems. Diagn. Microbiol. Infect. Dis. 2017, 88, 23–25. [Google Scholar] [CrossRef] [PubMed]
  56. Hinse, D.; Vollmer, T.; Erhard, M.; Welker, M.; Moore, E.R.; Kleesiek, K.; Dreier, J. Differentiation of Species of the Streptococcus bovis/equinus-Complex by MALDI-TOF Mass Spectrometry in Comparison to sodA Sequence Analyses. Syst. Appl. Microbiol. 2011, 34, 52–57. [Google Scholar] [CrossRef] [PubMed]
  57. López Roa, P.; Sánchez Carrillo, C.; Marín, M.; Romero, F.; Cercenado, E.; Bouza, E. Value of Matrix-Assisted Laser Desorption Ionization-Time of Flight for Routine Identification of viridans Group Streptococci Causing Bloodstream Infections. Clin. Microbiol. Infect. 2013, 19, 438–444. [Google Scholar] [CrossRef]
  58. Kärpänoja, P.; Harju, I.; Rantakokko-Jalava, K.; Haanperä, M.; Sarkkinen, H. Evaluation of Two Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Systems for Identification of viridans Group Streptococci. Eur. J. Clin. Microbiol. Infect. Dis. 2014, 33, 779–788. [Google Scholar] [CrossRef]
  59. Ogier, J.C.; Serror, P. Safety assessment of dairy microorganisms: The Enterococcus genus. Int. J. Food Microbiol. 2008, 126, 291–301. [Google Scholar] [CrossRef]
  60. Tripodi, M.F.; Fortunato, R.; Utili, R.; Triassi, M.; Zarrilli, R. Molecular Epidemiology of Streptococcus bovis Causing Endocarditis and Bacteraemia in Italian Patients. Clin. Microbiol. Infect. 2005, 1, 814–919. [Google Scholar] [CrossRef]
  61. Peretz, A.; Dinisman-Zavulunov, E.; Koifman, A.; Brodsky, D.; Isakovich, N.; Glyatman, T.; Pastukh, N.; Paritsky, M. Susceptibility of 45 Streptococcus bovis Isolates to Five Antibiotic Agents. Int. J. Antimicrob. Agents 2014, 43, 298–299. [Google Scholar] [CrossRef]
  62. Nomoto, R.; Tien Le, H.T.; Sekizaki, T.; Osawa, R. Antimicrobial Susceptibility of Streptococcus gallolyticus Isolated from Humans and Animals. Jpn. J. Infect. Dis. 2013, 66, 334–336. [Google Scholar] [CrossRef]
  63. Streit, J.M.; Steenbergen, J.N.; Thorne, G.M.; Alder, J.; Jones, R.N. Daptomycin Tested Against 915 Bloodstream Isolates of viridans Group Streptococci (eight species) and Streptococcus bovis. J. Antimicrob. Chemother. 2005, 55, 574–578. [Google Scholar] [CrossRef] [PubMed]
  64. Yap, D.Y.; To, K.K.; Yip, T.P.; Lui, S.L.; Chan, T.M.; Lai, K.N.; Lo, W.K. Streptococcus bovis Peritonitis Complicating Peritoneal Dialysis—A Review of 10 Years’ Experience. Perit. Dial. Int. 2012, 32, 55–59. [Google Scholar] [CrossRef] [PubMed]
  65. Teng, L.J.; Hsueh, P.R.; Ho, S.W.; Luh, K.T. High Prevalence of Inducible Erythromycin Resistance among Streptococcus bovis isolates in Taiwan. Antimicrob. Agents Chemother. 2001, 45, 3362–3365. [Google Scholar] [CrossRef]
  66. Leclercq, R.; Huet, C.; Picherot, M.; Trieu-Cuot, P.; Poyart, C. Genetic Basis of Antibiotic Resistance in Clinical Isolates of Streptococcus gallolyticus (Streptococcus bovis). Antimicrob. Agents Chemother. 2005, 49, 1646–1648. [Google Scholar] [CrossRef]
  67. Romero-Hernández, B.; Tedim, A.P.; Sánchez-Herrero, J.F.; Librado, P.; Rozas, J.; Muñoz, G.; Baquero, F.; Cantón, R.; Del Campo, R. Streptococcus gallolyticus subsp. gallolyticus from Human and Animal Origins: Genetic Diversity, Antimicrobial Susceptibility, and Characterization of a Vancomycin-Resistant Calf Isolate Carrying a vanA-Tn1546-Like Element. Antimicrob. Agents Chemother. 2015, 59, 2006–2015. [Google Scholar] [PubMed]
  68. Corredoira, J.; Alonso, M.P.; Coira, A.; Casariego, E.; Arias, C.; Alonso, D.; Pita, J.; Rodriguez, A.; López, M.J.; Varela, J. Characteristics of Streptococcus bovis Endocarditis and Its Differences with Streptococcus viridans Endocarditis. Eur. J. Clin. Microbiol. Infect. Dis. 2008, 27, 285–291. [Google Scholar] [CrossRef]
  69. Corredoira, J.C.; Alonso, M.P.; García, J.F.; Casariego, E.; Coira, A.; Rodriguez, A.; Pita, J.; Louzao, C.; Pombo, B.; López, M.J.; et al. Clinical Characteristics and Significance of Streptococcus salivarius Bacteremia and Streptococcus bovis Bacteremia: A Prospective 16-Year Study. Eur. J. Clin. Microbiol. Infect. Dis. 2005, 24, 250–255. [Google Scholar] [CrossRef]
  70. Tsai, J.C.; Hsueh, P.R.; Chen, H.J.; Tseng, S.P.; Chen, P.Y.; Teng, L.J. The erm(T) Gene is Flanked by IS1216V in Inducible Erythromycin-Resistant Streptococcus gallolyticus subsp. pasteurianus. Antimicrob. Agents Chemother. 2005, 49, 4347–4350. [Google Scholar] [CrossRef]
  71. Li, M.; Cai, C.; Chen, J.; Cheng, C.; Cheng, G.; Hu, X.; Liu, C. Inducible Expression of both ermB and ermT Conferred High Macrolide Resistance in Streptococcus gallolyticus subsp. pasteurianus Isolates in China. Int. J. Mol. Sci. 2016, 17, 1599. [Google Scholar] [CrossRef]
  72. Barile, S.; Devirgiliis, C.; Perozzi, G. Molecular Characterization of a Novel Mosaic tet(S/M) Gene Encoding Tetracycline Resistance in Foodborne Strains of Streptococcus bovis. Microbiology 2012, 158, 2353–2362. [Google Scholar] [CrossRef] [PubMed]
  73. Kambarev, S.; Pecorari, F.; Corvec, S. Novel Tn916-like Elements Confer Aminoglycoside/Macrolide Co-Resistance in Clinical Isolates of Streptococcus gallolyticus ssp. gallolyticus. J. Antimicrob. Chemother. 2018, 73, 1201–1205. [Google Scholar] [CrossRef]
  74. Khan, A. Relative Penicillin Resistance in Streptococcus bovis. A Case of Neonatal Meningitis. J. Paediatr. Child Health 2009, 45, 474–475. [Google Scholar] [PubMed]
  75. Poyart, C.; Pierre, C.; Quesne, G.; Pron, B.; Berche, P.; Trieu-Cuot, P. Emergence of Vancomycin Resistance in the Genus Streptococcus: Characterization of a vanB Transferable Determinant in Streptococcus bovis. Antimicrob. Agents Chemother. 1997, 41, 24–29. [Google Scholar] [CrossRef] [PubMed]
  76. Mevius, D.; Devriese, L.; Butaye, P.; Vandamme, P.; Verschure, M.; Veldman, K. Isolation of Glycopeptide Resistant Streptococcus gallolyticus Strains with vanA, vanB, and both vanA and vanB Genotypes from Fecal Samples of Veal Calves in The Netherlands. J. Antimicrob. Chemother. 1998, 42, 275–276. [Google Scholar] [CrossRef] [PubMed]
  77. Dahl, K.H.; Sundsfjord, A. Transferable vanB2 Tn5382-Containing Elements in Fecal Streptococcal Strains from Veal Calves. Antimicrob. Agents Chemother. 2003, 47, 2579–2583. [Google Scholar] [CrossRef]
Table
Table 1. Identification methods reported in the literature for SBSEC isolates.
Table 1. Identification methods reported in the literature for SBSEC isolates.
Identification MethodS. alactolyticusS. equinusS. gallolyticus subsp. gallolyticusS. gallolyticus subsp. macedonicusS. gallolyticus subsp. pasteurianusS. infantarius subsp. infantariusS. lutetiensis (S. infantarius subsp. coli)ReferenceComments
Phenotypic Rarely used. Lack of revised nomenclature in culture collection deposits and imperfect updates of databases.
Rapid ID 32 Strep (bioMérieux)+/-------[17,33,39]
Vitek 2 GP ID Card (bioMérieux)+/-+/-+/--+/-+/-+/-[14,17,21,22,43,47]
Genotypic a Generally based on gene PCR and sequencing. Partial sequences of rpoB, sodA, groEL, and gyrB are more discriminative than 16S rRNA gene sequence, with groEL representing the best performer. Absence of curated sequencing databases and lack of revised nomenclature in culture collection strains.
16S rRNAn.a.+++++/-+/-[14,19,22,39,43,45,46,48,58]
soda+++++++[19,22,33,40,43,56,57]
rpsBn.a.n.a.+n.a.+n.a.n.a.[21]
gyrB+++++++[40,51]
16S-23S ITS Rn.a.++++++[23,55]
tanBn.a.n.a.+n.a.n.a.n.a.n.a.[52]
SGPB0680n.a.n.a.n.a.n.a.+n.a.n.a.[52]
rpoB+++++++[40]
groES/ELb+++++++[40,43,47]
rnpBn.a.n.a.+n.a.+n.a.n.a.[44]
recNcn.a.n.a.+n.a.+++[51]
MLST d+++++++[5,42]
Proteomic Very fast and cheap, but highly dependent on the system, spectral databases and algorithms used
MALDI TOF Bruker Biotypern.a.---+/--+[19,44,45,46,55,57,58]
MALDI TOF Vitek MS++++/-+/-++[44,45,46,55,56,58]
From the literature a given method has been reported to: correctly identify SBSEC isolates to the species/subspecies level with high probability (“+”); be not able to correctly identify isolates to the species/subspecies level or correctly identify isolates with low probability (“-“); show discordant results (“+/-”); “n.a.” indicates that the SBSEC species/subspecies was not tested by the corresponding method. ITS R: interspacer region. a Genotypic methods are mainly based on gene PCR and sequencing. For 16S rRNA gene restriction fragment length polymorphism (RFLP) analysis has been also reported [48]. For gyrB gene real-time PCR without sequencing has been also described [51]. Refer to the text for details. b RFLP analysis of groESL gene has been also described [43,47]. c Real-time PCR for recN gene has been described [51]. d Multilocus Sequence Typing (MLST) based on PCR and sequencing of 7 housekeeping genes (dpr, gmk, rpoD, parC, pta, pyrC, recN) [42] or 10 housekeeping loci (ddlA, gki, glnA, mutS, mutS2, pheS, proS, pyrE, thrS, tpiA) [5].
Table
Table 2. Antibiotic resistance rates and resistance genes reported in the literature regarding species belonging to the Streptococcus bovis/Streptococcus equinus complex (SBSEC).
Table 2. Antibiotic resistance rates and resistance genes reported in the literature regarding species belonging to the Streptococcus bovis/Streptococcus equinus complex (SBSEC).
Isolates (n)Origin (Human or Animal)Body SiteStudy PeriodSBSEC Species/
Subspecies (n) a		Ery-R (%)Ery-R Gene (%)Cli-R (%)Tetracyclines-R (%) bTet-R Gene cOther Antibiotics (%) dCountryRef.
22HumanVarious2010–2012SGSP (22)31.8erm(B) (100)31.868.2tet(O)
tet(M)		Pen (0)
Ctx (0)
Van (0)		Italy[46]
25HumanBlood1990–2003SGSG (20)
SGSP (4)
SI (1)		48n.a.hn.a.64n.a.Gen (8)
Lev (4)
Pen (0)
Van (0)
in (0)		Italy[60]
45HumanBlood2003–2010SGSG (14)
SGSP (24)
SISI (2)
SL (5)		33.3n.d.30.2n.a.n.a.Sxt (20.2)
Lev (15.6)
Pen (0)
Str (0)
Rif (0)
Li (0)
Q-D (0)		Spain[19]
100HumanBloodn.a.S. bovis46n.a.2665n.a.Pen (3)
Van (0)
Lin (0)
Dap (0)
Q-D (6)		International collection[63]
45HumanCarriagen.a.S. bovis8.9n.a.n.d.n.a.n.a.Pen (13.3)
Cro (0)
Van (0)		Israel[61]
48HumanBlood1996–2001SGSG (2)
SGSP (42)
SI (4)		65erm(B) (54.2)
erm(T) (41.7)
erm(B)+erm(T) (4.2)		41n.a.n.a.Pen (0)
Van (0)		China[24]
23HumanPeritoneal dialysis2000–2010S. bovis47.8n.a.43.5n.a.n.a.Pen (30.4)China[64]
172HumanBlood2000–2012SGSG (126)
SGSP (31)
SI (15)		54.7n.a.54.1n.a.n.a.Gen (19.8)
Lev (16.9)
Pen (0.6)
Cro (0)
Van (0)
Lin (0)
Dap (0)
Tig (0)		Taiwan[43]
60HumanBlood1996–2000SGSG (4)
SGSP (53)
SI (3)		63.3erm(B) (63.2)
erm(T) (36.8)		63.375tet(M) ePen (0)
Ctx (0)
Van (0)
Chl (0)		Taiwan[65]
66Human (20) Animal (44) Reference (2)Various1981–2011SG16.7erm(B) (63.7)mef(A) (9.1) erm(B)+mef(A) (9.1) no genes (18.2)10.657.6tet(M)
tet(O)
tet(L)
tet(T)		Ctx:15.2
Chl:4.5
Pen:0
an:0		Japan[62]
128Human (125) Animal (3)Blood or cardiac biopsy1994–2003SGSG (121)
SGSP (3)
SI (2)
SL (2)		59.4erm(B) (96.1) erm(B)+mef(A) (2.6) mef(A) (1.3)58.677.7tet(M) tet(M)+tet(L)+tet(O) tet(M)+tet(O) tet(M)+tet(L) tet(O)
tet(L)		Pen (0)
Van (0)
Gen (0)
Rif (0)		France Belgium Netherlands[66]
118HumanUrine2003–2012SGSG (15)
SGSP (85)
SI (18)		48n.a.4575 fn.a.Sxt (98)
Fos (23)
Lev (16)
Nit (2)
Pen (0)
Ctx (0)		Spain[20]
41Human (18) Animal (23)Various1990–2010SGSG46.3erm(B) (94.7)
o genes (5.1)		48.836.6 gtet(M)Fos (51.2)
Q-D (14.6)
Gen (12.2)
Lev (12.2)
Sxt (7.3)
Van (2.4)		Spain[67]
107HumanBlood1988–2005SGSG (69)
SGSP (38)		60.2n.a.54.5n.a.n.a.Sxt (85.3)
Pen (0)		Spain[68]
64HumanBlood1987–2003SGSG (42)
SGSP (22)		60n.a.50n.a.n.a.Sxt (60)
Pen (0)
Ctx (0)
Van (0)		Spain[69]
18HumanBlood1998–2003S. bovis78erm(B) (92.9)
mef(A) (7.1)		72n.a.n.a.Tel (39)
Pen (11)		Spain[25]
Abbreviations: SG: Streptococcus gallolyticus; SGSG: S. gallolyticus subsp. gallolyticus; SGSP: S. gallolyticus subsp. pasteurianus; SI: Streptococcus infantarius; SISI: Streptococcus infantarius subsp. infantarius; SL: Streptococcus lutetiensis; Pen: Penicillin; Ctx: Cefotaxime; Cro: Ceftriaxone; Van: Vancomycin; Gen: Gentamycin; Lev: Levofloxacin; Lin: Linezolid; Sxt: Trimethoprim/Sulfamethoxazole; Str: Streptomycin; Rif: Rifampicin; Q-D: Quinupristin-Dalfopristin; Dap: Daptomycin; Tig: Tigecycline; Chl: Chloramphenicol; Fos: Fosfomycin; Nit: Nitrofurantoin; Tel: Telithromycin. a S. bovis indicates that the species/subspecies were not reported in that study. b Tetracyclines refer mainly to tetracycline. When others are tested, i.e., doxycycline or minocycline, these are indicated (see footnotes “f” and “g”). c Tetracycline resistance genes are listed in order of frequency reported in each study, and relative percentages are not indicated. d Resistance rates to other antibiotics tested in each study, excluded erythromycin, clindamycin, and tetracyclines. Isolates with reduced susceptibility to penicillin and cephalosporins, such as cefotaxime and ceftriaxone, are also included. e The presence of tetracycline resistance genes is evaluated only for erythromycin-resistant isolates. f Doxycycline has been tested in that study. g Minocycline has been tested in that study. h n.a.: not available.

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MDPI and ACS Style

Pompilio, A.; Di Bonaventura, G.; Gherardi, G. An Overview on Streptococcus bovis/Streptococcus equinus Complex Isolates: Identification to the Species/Subspecies Level and Antibiotic Resistance. Int. J. Mol. Sci. 2019, 20, 480. https://doi.org/10.3390/ijms20030480

AMA Style

Pompilio A, Di Bonaventura G, Gherardi G. An Overview on Streptococcus bovis/Streptococcus equinus Complex Isolates: Identification to the Species/Subspecies Level and Antibiotic Resistance. International Journal of Molecular Sciences. 2019; 20(3):480. https://doi.org/10.3390/ijms20030480

Chicago/Turabian Style

Pompilio, Arianna, Giovanni Di Bonaventura, and Giovanni Gherardi. 2019. "An Overview on Streptococcus bovis/Streptococcus equinus Complex Isolates: Identification to the Species/Subspecies Level and Antibiotic Resistance" International Journal of Molecular Sciences 20, no. 3: 480. https://doi.org/10.3390/ijms20030480

APA Style

Pompilio, A., Di Bonaventura, G., & Gherardi, G. (2019). An Overview on Streptococcus bovis/Streptococcus equinus Complex Isolates: Identification to the Species/Subspecies Level and Antibiotic Resistance. International Journal of Molecular Sciences, 20(3), 480. https://doi.org/10.3390/ijms20030480

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