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New Insight in Pathogenic Escherichia coli: Infections, Pathogenesis and...
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New Insight in Pathogenic Escherichia coli: Infections, Pathogenesis and Therapies

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 12289

Special Issue Editor

Dr. Bogdan Nowicki

E-Mail Website
Guest Editor
Department of Obstetrics and Gynecology, UT Medical Branch at Galveston, Galveston, TX 77555, USA
Interests: Escherichia coli; urinary tract infection; chronic sinusitis

Special Issue Information

Dear Colleagues,

Escherichia coli plays a causal role in chronic and/or recurrent urogenital infections. Chronic and/or recurrent E. coli infections may involve a broad spectrum of systems including the urinary bladder, kidney, gastrointestinal, vascular, respiratory, or even sinus tract. Over recent decades, novel strategies/techniques of biochemistry, molecular and cellular biology, microbiology, immunology, pathology, experimental in vitro or in vivo models and epidemiology have been used to explore the virulence of uro-pathogenic E. coli. These strategies uncovered significant, perhaps fundamental, mechanisms of uro-pathogenic E. coli adhesins-receptor mediated attachment, receptor mediated invasion and intracellular persistence and/or resistance.  

In parallel, studies of host biology uncovered the critical importance of human factors such as nitric oxide, TLR4, complement activation/inhibition cascade and steroid hormones in regulating immune systems exploited by E. coli to establish infection. Cyclic changes of steroid hormones while increasing expression of tissue receptors protecting the female or implanted fetus may be exploited by a pathogen for attachment/invasion. Immune network crosstalk in response to infection, impacts host risk for injury, contributing to the mechanism of chronic/recurrent E. coli renal injury, recurrent cystitis or increases the risk of feto-maternal health due to E. coli infectious complications. This host–pathogen interplay controls human health and disease, resulting in morbidity and/or mortality caused by E. coli infection.  

Respectively, we focus this Special Issue on changing paradigms across broad biomedical fields that are crucial for understanding pathogenesis, diagnosis and therapeutic strategies for reduction of E. coli chronic/recurrent infections resulting in human morbidity and mortality. 

Dr. Bogdan Nowicki
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (7 papers)

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Research

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18 pages, 4287 KiB  
Article
Therapeutic Effects of IL-1RA against Acute Bacterial Infections, including Antibiotic-Resistant Strains
by Ines Ambite, Thi Hien Tran, Daniel S. C. Butler, Michele Cavalera, Murphy Lam Yim Wan, Shahram Ahmadi and Catharina Svanborg
Pathogens 2024, 13(1), 42; https://doi.org/10.3390/pathogens13010042 - 31 Dec 2023
Viewed by 1749
Abstract
Innate immunity is essential for the anti-microbial defense, but excessive immune activation may cause severe disease. In this study, immunotherapy was shown to prevent excessive innate immune activation and restore the anti-bacterial defense. E. coli-infected Asc−/− mice develop severe acute cystitis, [...] Read more.
Innate immunity is essential for the anti-microbial defense, but excessive immune activation may cause severe disease. In this study, immunotherapy was shown to prevent excessive innate immune activation and restore the anti-bacterial defense. E. coli-infected Asc−/− mice develop severe acute cystitis, defined by IL-1 hyper-activation, high bacterial counts, and extensive tissue pathology. Here, the interleukin-1 receptor antagonist (IL-1RA), which inhibits IL-1 hyper-activation in acute cystitis, was identified as a more potent inhibitor of inflammation and NK1R- and substance P-dependent pain than cefotaxime. Furthermore, IL-1RA treatment inhibited the excessive innate immune activation in the kidneys of infected Irf3−/− mice and restored tissue integrity. Unexpectedly, IL-1RA also accelerated bacterial clearance from infected bladders and kidneys, including antibiotic-resistant E. coli, where cefotaxime treatment was inefficient. The results suggest that by targeting the IL-1 response, control of the innate immune response to infection may be regained, with highly favorable treatment outcomes, including infections caused by antibiotic-resistant strains. Full article
(This article belongs to the Special Issue New Insight in Pathogenic Escherichia coli: Infections, Pathogenesis and Therapies)
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16 pages, 2816 KiB  
Article
Effect of Gravity on Bacterial Adhesion to Heterogeneous Surfaces
by Kayla Hogan, Sai Paul, Guanyou Lin, Jay Fuerte-Stone, Evgeni V. Sokurenko and Wendy E. Thomas
Pathogens 2023, 12(7), 941; https://doi.org/10.3390/pathogens12070941 - 15 Jul 2023
Cited by 1 | Viewed by 1034
Abstract
Bacterial adhesion is the first step in the formation of surface biofilms. The number of bacteria that bind to a surface from the solution depends on how many bacteria can reach the surface (bacterial transport) and the strength of interactions between bacterial adhesins [...] Read more.
Bacterial adhesion is the first step in the formation of surface biofilms. The number of bacteria that bind to a surface from the solution depends on how many bacteria can reach the surface (bacterial transport) and the strength of interactions between bacterial adhesins and surface receptors (adhesivity). By using microfluidic channels and video microscopy as well as computational simulations, we investigated how the interplay between bacterial transport and adhesivity affects the number of the common human pathogen Escherichia coli that bind to heterogeneous surfaces with different receptor densities. We determined that gravitational sedimentation causes bacteria to concentrate at the lower surface over time as fluid moves over a non-adhesive region, so bacteria preferentially adhere to adhesive regions on the lower, inflow-proximal areas that are downstream of non-adhesive regions within the entered compartments. Also, initial bacterial attachment to an adhesive region of a heterogeneous lower surface may be inhibited by shear due to mass transport effects alone rather than shear forces per se, because higher shear washes out the sedimented bacteria. We also provide a conceptual framework and theory that predict the impact of sedimentation on adhesion between and within adhesive regions in flow, where bacteria would likely bind both in vitro and in vivo, and how to normalize the bacterial binding level under experimental set-ups based on the flow compartment configuration. Full article
(This article belongs to the Special Issue New Insight in Pathogenic Escherichia coli: Infections, Pathogenesis and Therapies)
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13 pages, 2673 KiB  
Article
Effect of Mannan Oligosaccharides Extracts in Uropathogenic Escherichia coli Adhesion in Human Bladder Cells
by Margarida Faustino, Sara Silva, Eduardo M. Costa, Ana Margarida Pereira, Joana Odila Pereira, Ana Sofia Oliveira, Carlos M. H. Ferreira, Carla F. Pereira, Joana Durão, Manuela E. Pintado and Ana P. Carvalho
Pathogens 2023, 12(7), 885; https://doi.org/10.3390/pathogens12070885 - 28 Jun 2023
Cited by 1 | Viewed by 1592
Abstract
Urinary tract infections (UTIs) are a common public health problem, mainly caused by uropathogenic Escherichia coli (UPEC). Patients with chronic UTIs are usually treated with long-acting prophylactic antibiotics, which promotes the development of antibiotic-resistant UPEC strains and may complicate their long-term management. D-mannose [...] Read more.
Urinary tract infections (UTIs) are a common public health problem, mainly caused by uropathogenic Escherichia coli (UPEC). Patients with chronic UTIs are usually treated with long-acting prophylactic antibiotics, which promotes the development of antibiotic-resistant UPEC strains and may complicate their long-term management. D-mannose and extracts rich in D-mannose such as mannan oligosaccharides (MOS; D-mannose oligomers) are promising alternatives to antibiotic prophylaxis due to their ability to inhibit bacterial adhesion to urothelial cells and, therefore, infection. This highlights the therapeutic potential and commercial value of using them as health supplements. Studies on the effect of MOS in UTIs are, however, scarce. Aiming to evaluate the potential benefits of using MOS extracts in UTIs prophylaxis, their ability to inhibit the adhesion of UPEC to urothelial cells and its mechanism of action were assessed. Additionally, the expression levels of the pro-inflammatory marker interleukin 6 (IL-6) were also evaluated. After characterizing their cytotoxic profiles, the preliminary results indicated that MOS extracts have potential to be used for the handling of UTIs and demonstrated that the mechanism through which they inhibit bacterial adhesion is through the competitive inhibition of FimH adhesins through the action of mannose, validated by a bacterial growth impact assessment. Full article
(This article belongs to the Special Issue New Insight in Pathogenic Escherichia coli: Infections, Pathogenesis and Therapies)
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13 pages, 1269 KiB  
Article
Colonization with Escherichia coli ST131-H30R (H30R) Corresponds with Increased Serum Anti-O25 IgG Levels and Decreased TNFα and IL-10 Responsiveness to H30R
by Brian D. Johnston, Connie Clabots, Tricia Bender, Stephen B. Porter, Germie van den Dobbelsteen, Jan Poolman, Paul Thuras and James R. Johnson
Pathogens 2023, 12(4), 603; https://doi.org/10.3390/pathogens12040603 - 15 Apr 2023
Viewed by 1255
Abstract
An exceptional gut-colonizing ability may underlie the dramatic epidemiological success of the multidrug-resistant H30R subclone of Escherichia coli sequence type 131 (O25b:K+:H4). In order to inform the development of colonization-preventing measures, we studied systemic immune correlates of H30R intestinal colonization. Human [...] Read more.
An exceptional gut-colonizing ability may underlie the dramatic epidemiological success of the multidrug-resistant H30R subclone of Escherichia coli sequence type 131 (O25b:K+:H4). In order to inform the development of colonization-preventing measures, we studied systemic immune correlates of H30R intestinal colonization. Human volunteers’ fecal samples were screened for H30R by selective culture and PCR. Subjects were assessed by enzyme immunoassay for serum levels of anti-O25 IgG (representing H30R) and anti-O6 IgG (representing non-H30 E. coli generally), initially and for up to 14 months. Whole blood was tested for the antigen-stimulated release of IFNγ, TNFα, IL-4, IL-10, and IL-17 after incubation with E. coli strains JJ1886 (H30R; O25b:K+:H4) or CFT073 (non-H30; O6:K2:H1). Three main findings were obtained. First, H30R-colonized subjects had significantly higher anti-O25 IgG levels than controls, but similar anti-O6 IgG levels, suggesting an IgG response to H30R colonization. Second, anti-O25 and anti-O6 IgG levels were stable over time. Third, H30R-colonized subjects exhibited a lower TNFα and IL-10 release than controls in response to strain JJ1886 (H30R) relative to strain CFT073 (non-H30R), consistent with TNFα hypo-responsiveness to H30R possibly predisposing to H30R colonization. Thus, H30R-colonized hosts exhibit a sustained serum anti-O25 IgG response and an underlying deficit in TNFα responsiveness to H30R that could potentially be addressed for colonization prevention. Full article
(This article belongs to the Special Issue New Insight in Pathogenic Escherichia coli: Infections, Pathogenesis and Therapies)
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13 pages, 1418 KiB  
Article
Strong Association between Diarrhea and Concentration of Enterotoxigenic Escherichia coli Strain TW10722 in Stools of Experimentally Infected Volunteers
by Oda Barth Vedøy, Hans Steinsland, Sunniva Todnem Sakkestad, Halvor Sommerfelt and Kurt Hanevik
Pathogens 2023, 12(2), 283; https://doi.org/10.3390/pathogens12020283 - 8 Feb 2023
Cited by 4 | Viewed by 1566
Abstract
Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrheal illness in children and travelers in low- and middle-income countries. When volunteers are infected with ETEC strains, as part of experimental infection studies, some do not develop diarrhea. To improve our understanding [...] Read more.
Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrheal illness in children and travelers in low- and middle-income countries. When volunteers are infected with ETEC strains, as part of experimental infection studies, some do not develop diarrhea. To improve our understanding of how these volunteers are protected, we investigated the association between stool ETEC DNA concentration, as determined by quantitative PCR, and the development and severity of disease in 21 volunteers who had been experimentally infected with ETEC strain TW10722. We found a strong association between maximum stool ETEC DNA concentration and the development of diarrhea: all of the 11 volunteers who did not develop diarrhea had <0.99% TW10722-specific DNA in their stools throughout the follow-up period of up to 9 days, while all of the 10 volunteers who did develop diarrhea had maximum DNA concentrations of ≥0.99%. Most likely, these maximum stool TW10722 DNA concentrations reflect the level of intestinal colonization and the risk of experiencing diarrhea, thereby, seems to be directly dependent on the level of colonization. Thus, the development and availability of vaccines and other prophylactic measures, even if they only partially reduce colonization, could be important in the effort to reduce the burden of ETEC diarrhea. Full article
(This article belongs to the Special Issue New Insight in Pathogenic Escherichia coli: Infections, Pathogenesis and Therapies)
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Review

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22 pages, 926 KiB  
Review
Avian Pathogenic Escherichia coli (APEC) in Broiler Breeders: An Overview
by Jiddu Joseph, Li Zhang, Pratima Adhikari, Jeffrey D. Evans and Reshma Ramachandran
Pathogens 2023, 12(11), 1280; https://doi.org/10.3390/pathogens12111280 - 26 Oct 2023
Cited by 2 | Viewed by 3499
Abstract
Poultry meat is one of the major animal protein sources necessary to meet the global protein demand. Sustainability in broiler production is the key to achieving its continuous supply, and broiler breeders play a critical role in maintaining this sustainability by providing good [...] Read more.
Poultry meat is one of the major animal protein sources necessary to meet the global protein demand. Sustainability in broiler production is the key to achieving its continuous supply, and broiler breeders play a critical role in maintaining this sustainability by providing good quality chicks. Colibacillosis, the disease caused by avian pathogenic Escherichia coli (APEC), causes severe economic losses to the poultry industry globally. Moreover, APEC causes an additional burden among broiler breeders, such as a decrease in egg production and mortality among these birds. There is vertical transmission of APEC to the broiler chicks through eggs, resulting in increased first-week mortality and subsequent horizontal transmission at the hatchery. In this regard, the vertical transmission of antibiotic resistance genes is another concern that needs attention. Controlling several diseases in broiler breeders would possibly reduce the first-week mortality in chicks, thereby maintaining the production level. For that, constant monitoring of the bacterial populations is critical. Moreover, amidst the increased antibiotic resistance pattern, more focus on alternative treatment strategies like vaccines, probiotics, and bacteriophages is necessary. Future research focusing on strategies to mitigate APEC in broiler breeders would be one of the finest solutions for sustainable broiler production. Full article
(This article belongs to the Special Issue New Insight in Pathogenic Escherichia coli: Infections, Pathogenesis and Therapies)
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Other

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10 pages, 275 KiB  
Opinion
Commensal Fitness Advantage May Contribute to the Global Dissemination of Multidrug-Resistant Lineages of Bacteria—The Case of Uropathogenic E. coli
by Miklos Fuzi and Evgeni Sokurenko
Pathogens 2023, 12(9), 1150; https://doi.org/10.3390/pathogens12091150 - 10 Sep 2023
Cited by 2 | Viewed by 891
Abstract
It is widely accepted that favorable fitness in commensal colonization is one of the prime facilitators of clonal dissemination in bacteria. The question arises as to what kind of fitness advantage may be wielded by uropathogenic strains of the two predominant fluoroquinolone- and [...] Read more.
It is widely accepted that favorable fitness in commensal colonization is one of the prime facilitators of clonal dissemination in bacteria. The question arises as to what kind of fitness advantage may be wielded by uropathogenic strains of the two predominant fluoroquinolone- and multidrug-resistant clonal groups of E. coli—ST131-H30 and ST1193, which has permitted their unprecedented pandemic-like global expansion in the last few decades. The colonization-associated genes’ content, carriage of low-cost plasmids, and integrons with weak promoters could certainly contribute to the fitness of the pandemic groups, although those genetic factors are common among other clonal groups as well. Also, ST131-H30 and ST1193 strains harbor fluoroquinolone-resistance conferring mutations targeting serine residues in DNA gyrase (GyrA-S83) and topoisomerase IV (ParC-S80) that, in those clonal backgrounds, might result in a commensal fitness benefit, i.e., beyond the antibiotic resistance per se. This fitness gain might have contributed not only to the widespread dissemination of these major clones in the healthcare setting but also to their long-term colonization of healthy individuals and, thus, circulation in the community, even in a low or no fluoroquinolone use environment. This evolutionary shift affecting commensal E. coli, initiated by mutations co-favorable in both antibiotics-treated patients and healthy individuals warrants more in-depth studies to monitor further changes in the epidemiological situation and develop effective measures to reduce the antibiotic resistance spread. Full article
(This article belongs to the Special Issue New Insight in Pathogenic Escherichia coli: Infections, Pathogenesis and Therapies)
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