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      Multidrug- and Extensively Drug-Resistant Uropathogenic Escherichia coli Clinical Strains: Phylogenetic Groups Widely Associated with Integrons Maintain High Genetic Diversity

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          Abstract

          In recent years, an increase of uropathogenic Escherichia coli (UPEC) strains with Multidrug-resistant (MDR) and Extensively Drug-resistant (XDR) profiles that complicate therapy for urinary tract infections (UTIs) has been observed and has directly impacted costs and extended hospital stays. The aim of this study was to determine MDR- and XDR-UPEC clinical strains, their virulence genes, their phylogenetic groups and to ascertain their relationship with integrons and genetic diversity. From a collection of 500 UPEC strains, 103 were selected with MDR and XDR characteristics. MDR-UPEC strains were mainly associated with phylogenetic groups D (54.87%) and B2 (39.02%) with a high percentage (≥70%) of several fimbrial genes ( ecpA, fimH, csgA, and papGII), an iron uptake gene ( chuA), and a toxin gene ( hlyA). In addition, a moderate frequency (40–70%) of other genes ( iutD, tosA, and bcsA) was observed. XDR-UPEC strains were predominantly associated with phylogenetic groups B2 (47.61%) and D (42.85%), which grouped with ≥80 virulence genes, including ecpA, fimH, csgA, papGII, iutD, and chuA. A moderate frequency (40–70%) of the tosA and hlyA genes was observed. The class 1 and 2 integrons that were identified in the MDR- and XDR-UPEC strains were associated with phylogenetic groups D, B2, and A, while the XDR-UPEC strains that were associated with phylogenetic groups B2, D, and A showed an extended-spectrum beta-lactamase (ESBL) phenotype. The modifying enzymes ( aadA1, aadB, aacC, ant1, dfrA1, dfrA17, and aadA4) that were identified in the variable region of class 1 and 2 integrons from the MDR strains showed resistance to gentamycin (56.25 and 66.66%, respectively) and trimethoprim-sulfamethoxazole (84.61 and 66.66%, respectively). The MDR- and XDR-UPEC strains were distributed into seven clusters and were closely related to phylogenic groups B2 and D. The diversity analysis by PFGE showed 42.68% of clones of MDR-UPEC and no clonal association in the XDR-UPEC strains. In conclusion, phylogenetic groups including virulence genes are widely associated with two integron classes (1 and 2) in MDR- and XDR-UPEC strains.

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          Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation.

          Curli are functional extracellular amyloid fibers produced by uropathogenic Escherichia coli (UPEC) and other Enterobacteriaceae. Ring-fused 2-pyridones, such as FN075 and BibC6, inhibited curli biogenesis in UPEC and prevented the in vitro polymerization of the major curli subunit protein CsgA. The curlicides FN075 and BibC6 share a common chemical lineage with other ring-fused 2-pyridones termed pilicides. Pilicides inhibit the assembly of type 1 pili, which are required for pathogenesis during urinary tract infection. Notably, the curlicides retained pilicide activities and inhibited both curli-dependent and type 1-dependent biofilms. Furthermore, pretreatment of UPEC with FN075 significantly attenuated virulence in a mouse model of urinary tract infection. Curli and type 1 pili exhibited exclusive and independent roles in promoting UPEC biofilms, and curli provided a fitness advantage in vivo. Thus, the ability of FN075 to block the biogenesis of both curli and type 1 pili endows unique anti-biofilm and anti-virulence activities on these compounds.
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            Integron Involvement in Environmental Spread of Antibiotic Resistance

            The spread of antibiotic-resistant bacteria is a growing problem and a public health issue. In recent decades, various genetic mechanisms involved in the spread of resistance genes among bacteria have been identified. Integrons – genetic elements that acquire, exchange, and express genes embedded within gene cassettes (GC) – are one of these mechanisms. Integrons are widely distributed, especially in Gram-negative bacteria; they are carried by mobile genetic elements, plasmids, and transposons, which promote their spread within bacterial communities. Initially studied mainly in the clinical setting for their involvement in antibiotic resistance, their role in the environment is now an increasing focus of attention. The aim of this review is to provide an in-depth analysis of recent studies of antibiotic-resistance integrons in the environment, highlighting their potential involvement in antibiotic-resistance outside the clinical context. We will focus particularly on the impact of human activities (agriculture, industries, wastewater treatment, etc.).
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              Role of P-fimbrial-mediated adherence in pyelonephritis and persistence of uropathogenic Escherichia coli (UPEC) in the mammalian kidney.

              P fimbria, a mannose-resistant adhesin of uropathogenic Escherichia coli (UPEC), has been shown to be associated with acute pyelonephritis. The pap gene cluster encodes the proteins required for P-fimbrial biogenesis, including papG, which encodes the tip adhesin. The three most studied PapG molecular variants, which are shown to bind distinct isoreceptors, are PapGI, -II, and -III. PapGII preferentially binds globoside, or GbO4, a glycolipid isoreceptor of the human kidney. Studies using different animal models of ascending urinary tract infection (UTI) have demonstrated a variable role for P fimbriae, and specifically PapGII-mediated adherence, in renal colonization. The disparities in the results obtained from those studies are likely to be attributed to the differences in animal models and UPEC strains utilized. One explanation that is discussed in detail is the contribution of multiple fimbriae of UPEC that potentially mediate adherence to the mammalian kidney. Overall, P fimbriae appear to play some role in mediating adherence to uroepithelial cells in vivo and establishing an inflammatory response during renal colonization, thus contributing to kidney damage during acute pyelonephritis. To verify that P fimbriae contribute to the pathogenesis of UPEC during ascending UTI (and in particular acute pyelonephritis), future studies should be conducted to satisfy fully all three tenets of the molecular Koch's postulates, including complementation of a mutated allele.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                21 December 2016
                2016
                : 7
                : 2042
                Affiliations
                [1] 1Laboratorio de Investigación en Bacteriología Intestinal, Hospital Infantil de México Federico Gómez Mexico City, Mexico
                [2] 2Posgrado en Ciencias Químico-Biológicas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional Mexico City, Mexico
                [3] 3Laboratorio de Bacteriología Médica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional Mexico City, Mexico
                [4] 4Laboratorio de Estructura de Proteínas, Instituto Nacional de Medicina Genómica Mexico City, Mexico
                [5] 5Área de Virología, Laboratorio de Infectología, Hospital Infantil de México Federico Gómez Mexico City, Mexico
                [6] 6Subdirección de Servicios Auxiliares de Diagnóstico, Hospital Infantil de México Federico Gómez Mexico City, Mexico
                [7] 7Laboratorio Clínico, Hospital Infantil de México Federico Gómez Mexico City, Mexico
                [8] 8Departamento de Ecología de Agentes Patógenos, Hospital General “Dr. Manuel Gea González,” Mexico City, Mexico
                [9] 9Epidemiología Hospitalaria, Hospital Infantil de México Federico Gómez Mexico City, Mexico
                Author notes

                Edited by: Yuji Morita, Aichi Gakuin University, Japan

                Reviewed by: Sebastian Guenther, Free University of Berlin, Germany; Tatiana Amabile De Campos, Universidade de Brasília, Brazil

                *Correspondence: Juan Xicohtencatl-Cortes juanxico@ 123456yahoo.com

                This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2016.02042
                5174082
                28066364
                1b6f0ef9-3a6d-4c58-ad7f-7f8b1ffa7ab3
                Copyright © 2016 Ochoa, Cruz-Córdova, Luna-Pineda, Reyes-Grajeda, Cázares-Domínguez, Escalona, Sepúlveda-González, López-Montiel, Arellano-Galindo, López-Martínez, Parra-Ortega, Giono-Cerezo, Hernández-Castro, de la Rosa-Zamboni and Xicohtencatl-Cortes.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 05 September 2016
                : 05 December 2016
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 59, Pages: 12, Words: 8157
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                upec,multidrug resistance,virulence genes,phylogenetic groups,pfge
                Microbiology & Virology
                upec, multidrug resistance, virulence genes, phylogenetic groups, pfge

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