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      Special Issue: Pathogenic Escherichia coli: Infections and Therapies

      editorial
      Antibiotics
      MDPI

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          Abstract

          Escherichia coli is a facultative anaerobic Gram-negative bacterium from the Enterobacteriaceae family that colonizes the gastrointestinal tract of warm-blooded animals shortly after birth, and it is a lifelong colonizer of adults. This species persists as a harmless commensal in the mucous layer, interacting with the host in a mutualistic manner. However, there are certain strains with pathogenic properties that can cause disease, and, in turn, nonpathogenic intestinal E. coli can eventually cause or contribute to disease in compromised hosts. Pathogenic E. coli strains are grouped into pathotypes according to their clinical spectra and virulence factors. The extraintestinal pathogenic E. coli (ExPEC) group comprises the strains causing infections outside the intestinal tract, mainly infections in the urinary tract, but also sepsis, meningitis, and wound infections. These strains are genetically diverse and resemble nonpathogenic E. coli residing in the intestinal tract. Distinct from commensal and ExPEC strains, diarrhoeagenic E. coli (DEC) cause intestinal infections and harbor specific surface adhesins and other virulence factors, and they can be classified into seven well-defined pathotypes: enterohemorrhagic E. coli (EAEC), enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), enteroaggregative E. coli (EHEC), enteroinvasive E. coli (EIEC), diffusely adherent E. coli (DAEC), and necrotoxic E. coli (NTEC). Recently, a new pathotype called adherent-invasive E. coli (AIEC) has been proposed as being associated with inflammatory bowel disease, especially Crohn’s disease. As Gram-negative organisms, E. coli are resistant to many antibiotics, and high-risk E. coli multiresistant clones are emerging. Indeed, carbapenem-resistant extended-spectrum beta-lactamase (ESBL)-producing strains are considered to be of critical priority by the World Health Organization as bacterial pathogens for which new antibiotics should be designed. On the other hand, antibiotic treatments have profound effects on the human microbiome, and, thus, new strategies, such as very-narrow-spectrum treatments, antiadhesives, phage therapy, or vaccination, are welcomed. This Special Issue “Pathogenic Escherichia coli: Infections and Therapies” consists of 12 articles, including original research on intestinal pathologies and extraintestinal infections of human and animal origins caused by E. coli [1,2,3,4,5,6,7] and a review on FimH antiadhesive molecules that can be used to treat urinary tract infections caused by uropathogenic E. coli (UPEC) [8]. Apart from this review, other original articles propose novel approaches to treat and/or prevent E. coli infections. For instance, Zhang et al. suggest that colonic butyrate administration could be a novel treatment approach to decrease the growth and virulence gene expression of dysbiotic pathosimbiont E. coli in the context of inflammatory bowel disease [9]. Bumunang et al. propose bacteriophage therapy and phlorotannin as antimicrobials against biofilm-forming Shiga toxin-producing E. coli [10], and Alves et al. propose poly(MeOEGMA) as a polymer brush that prevents bacterial adhesion in urinary tract devices, such as ureteral stents and catheters, which has the potential to eradicate biofilms developed in these biomedical devices [11]. On the other hand, Mazurek-Popczyk et al. identify bacteriocin-producing E. coli in the human intestine and demonstrate that these strains have antibacterial activity against zoonotic E. coli, thus demonstrating the importance of these strains in hampering the colonization of the human intestine by animal strains and, therefore, in preventing zoonotic infections [12]. The focus of the Special Issue is rather wide; nonetheless, we do expect that this group of manuscripts will be of interest to the research community interested in pathogenic E. coli virulence properties, antimicrobial resistance mechanisms, transmission paths, and novel potential therapies and prevention approaches.

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          Most cited references12

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          FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against Uropathogens

          Chaperone-usher fimbrial adhesins are powerful weapons against the uropathogens that allow the establishment of urinary tract infections (UTIs). As the antibiotic therapeutic strategy has become less effective in the treatment of uropathogen-related UTIs, the anti-adhesive molecules active against fimbrial adhesins, key determinants of urovirulence, are attractive alternatives. The best-characterized bacterial adhesin is FimH, produced by uropathogenic Escherichia coli (UPEC). Hence, a number of high-affinity mono- and polyvalent mannose-based FimH antagonists, characterized by different bioavailabilities, have been reported. Given that antagonist affinities are firmly associated with the functional heterogeneities of different FimH variants, several FimH inhibitors have been developed using ligand-drug discovery strategies to generate high-affinity molecules for successful anti-adhesion therapy. As clinical trials have shown d-mannose’s efficacy in UTIs prevention, it is supposed that mannosides could be a first-in-class strategy not only for UTIs, but also to combat other Gram-negative bacterial infections. Therefore, the current review discusses valuable and effective FimH anti-adhesive molecules active against UTIs, from design and synthesis to in vitro and in vivo evaluations.
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            Short Chain Fatty Acids Modulate the Growth and Virulence of Pathosymbiont Escherichia coli and Host Response

            Short chain fatty acids (SCFA), principally acetate, propionate, and butyrate, are produced by fermentation of dietary fibers by the gut microbiota. SCFA regulate the growth and virulence of enteric pathogens, such as enterohemorrhagic E. coli (EHEC), Klebsiella and Salmonella. We sought to investigate the impact of SCFA on growth and virulence of pathosymbiont E. coli associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC), and their role in regulating host responses to bacterial infection in vitro. We found that under ileal conditions (pH = 7.4; 12 mM total SCFA), SCFA significantly (p < 0.05) potentiate the growth and motility of pathosymbiont E. coli. However, under colonic conditions (pH = 6.5; 65 to 123 mM total SCFA), SCFA significantly (p < 0.05) inhibit growth in a pH dependent fashion (up to 60%), and down-regulate virulence gene expression (e.g., fliC, fimH, htrA, chuA, pks). Functional analysis reveals that colonic SCFA significantly (p < 0.05) inhibit E. coli motility (up to 95%), infectivity (up to 60%), and type 1 fimbria-mediated agglutination (up to 50%). In addition, SCFA significantly (p < 0.05) inhibit the activation of NF-κB, and IL-8 production by epithelial cells. Our findings provide novel insights on the role of the regional chemical microenvironment in regulating the growth and virulence of pathosymbiont E. coli and opportunities for therapeutic intervention.
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              Clonal Structure, Virulence Factor-encoding Genes and Antibiotic Resistance of Escherichia coli , Causing Urinary Tract Infections and Other Extraintestinal Infections in Humans in Spain and France during 2016

              Escherichia coli is the main pathogen responsible for extraintestinal infections. A total of 196 clinical E. coli consecutively isolated during 2016 in Spain (100 from Lucus Augusti hospital in Lugo) and France (96 from Beaujon hospital in Clichy) were characterized. Phylogroups, clonotypes, sequence types (STs), O:H serotypes, virulence factor (VF)-encoding genes and antibiotic resistance were determined. Approximately 10% of the infections were caused by ST131 isolates in both hospitals and approximately 60% of these infections were caused by isolates belonging to only 10 STs (ST10, ST12, ST58, ST69, ST73, ST88, ST95, ST127, ST131, ST141). ST88 isolates were frequent, especially in Spain, while ST141 isolates significantly predominated in France. The 23 ST131 isolates displayed four clonotypes: CH40-30, CH40-41, CH40-22 and CH40-298. Only 13 (6.6%) isolates were carriers of extended-spectrum beta-lactamase (ESBL) enzymes. However, 37.2% of the isolates were multidrug-resistant (MDR). Approximately 40% of the MDR isolates belonged to only four of the dominant clones (B2-CH40-30-ST131, B2-CH40-41-ST131, C-CH4-39-ST88 and D-CH35-27-ST69). Among the remaining MDR isolates, two isolates belonged to B2-CH14-64-ST1193, i.e., the new global emergent MDR clone. Moreover, a hybrid extraintestinal pathogenic E.coli (ExPEC)/enteroaggregative isolate belonging to the A-CH11-54-ST10 clone was identified.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Antibiotics (Basel)
                Antibiotics (Basel)
                antibiotics
                Antibiotics
                MDPI
                2079-6382
                25 January 2021
                February 2021
                : 10
                : 2
                : 112
                Affiliations
                Microbiology of the Intestinal Disease, Biology Department, University of Girona, 17003 Girona, Spain; marga.martinez@ 123456udg.edu
                Author information
                https://orcid.org/0000-0003-0177-3307
                Article
                antibiotics-10-00112
                10.3390/antibiotics10020112
                7912384
                33504016
                b7e43b16-6c92-4cb6-9c3e-a3c58fed56b1
                © 2021 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 January 2021
                : 22 January 2021
                Categories
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