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      Phenotypic and Genotypic Characteristics of Uropathogenic Escherichia coli Isolates from Kenya

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          Abstract

          Introduction: Uropathogenic Escherichia coli (UPECs) are a significant cause of urinary tract infections (UTIs). In Kenya, UTIs are typically treated with β-lactam antibiotics without antibiotic susceptibility testing, which could accelerate antibiotic resistance among UPEC strains.

          Aim: This study determined the occurrence of UPEC producing extended-spectrum β-lactamases (ESBLs), the genes conferring resistance to β-lactams, and the phylogenetic groups associated with ESBLs in Kenyan UPECs.

          Methodology: Ninety-five UPEC isolates from six Kenyan hospitals were tested for ESBL and plasmid-mediated AmpC β-lactamase (pAmpC) production by combined disk diffusion and disk approximation tests, respectively. Real-time and conventional polymerase chain reactions (PCRs) were used to detect three ESBL and six pAmpC genes, respectively, and phylogenetic groups were assigned by a quadruplex PCR method.

          Results: Twenty-four percent UPEC isolates were ESBL producers with bla CTX-M (95.6%), bla TEM (95.6%), and bla SHV (21.7%) genes detected. Sixteen isolates had bla CTX-M/TEM, whereas five had bla TEM/CTX-M/SHV. A total of 5/23 ESBLs were cefoxitin resistant, but no AmpC genes were detected. The UPECs belonged predominantly to phylogenetic groups B2 (31/95; 32.6%) and D (30/95; 31.6%), while groups B2 and A had the most ESBL producers.

          Conclusions: β-Lactam antibiotics have reduced utility for treating UTIs as a quarter of UPECs were ESBL producing. Single or multiple ESBL genes were present in UPECs, belonging primarily to phylogenetic groups B2 and A.

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          The Clermont Escherichia coli phylo-typing method revisited: improvement of specificity and detection of new phylo-groups.

          There is extensive genetic substructure within the species Escherichia coli. In 2000 a simple triplex PCR method was described by Clermont and colleagues that enables an E. coli isolate to be assigned to one of the phylo-groups A, B1, B2 or D. The growing body of multi-locus sequence data and genome data for E. coli has refined our understanding of E. coli's phylo-group structure and eight phylo-groups are now recognized: seven (A, B1, B2, C, D, E, F) belong to E. coli sensu stricto, whereas the eighth is the Escherichia cryptic clade I. Here a new PCR-based method is developed that enables an E. coli isolate to be assigned to one of the eight phylo-groups and which allows isolates that are members of the other cryptic clades (II to V) of Escherichia to be identified. The development of the method is described and the method is validated. Over 95% of E. coli isolates can be correctly assigned to a phylo-group. Two collections of human faecal isolates were screened using the new phylo-group assignment method demonstrating that about 13% of E. coli isolates belong to the newly described phylo-groups C, E, F and clade I. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.
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            Mechanisms of antimicrobial resistance in Gram-negative bacilli

            The burden of multidrug resistance in Gram-negative bacilli (GNB) now represents a daily issue for the management of antimicrobial therapy in intensive care unit (ICU) patients. In Enterobacteriaceae, the dramatic increase in the rates of resistance to third-generation cephalosporins mainly results from the spread of plasmid-borne extended-spectrum beta-lactamase (ESBL), especially those belonging to the CTX-M family. The efficacy of beta-lactam/beta-lactamase inhibitor associations for severe infections due to ESBL-producing Enterobacteriaceae has not been adequately evaluated in critically ill patients, and carbapenems still stands as the first-line choice in this situation. However, carbapenemase-producing strains have emerged worldwide over the past decade. VIM- and NDM-type metallo-beta-lactamases, OXA-48 and KPC appear as the most successful enzymes and may threaten the efficacy of carbapenems in the near future. ESBL- and carbapenemase-encoding plasmids frequently bear resistance determinants for other antimicrobial classes, including aminoglycosides (aminoglycoside-modifying enzymes or 16S rRNA methylases) and fluoroquinolones (Qnr, AAC(6′)-Ib-cr or efflux pumps), a key feature that fosters the spread of multidrug resistance in Enterobacteriaceae. In non-fermenting GNB such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia, multidrug resistance may emerge following the sole occurrence of sequential chromosomal mutations, which may lead to the overproduction of intrinsic beta-lactamases, hyper-expression of efflux pumps, target modifications and permeability alterations. P. aeruginosa and A. baumannii also have the ability to acquire mobile genetic elements encoding resistance determinants, including carbapenemases. Available options for the treatment of ICU-acquired infections due to carbapenem-resistant GNB are currently scarce, and recent reports emphasizing the spread of colistin resistance in environments with high volume of polymyxins use elicit major concern. Electronic supplementary material The online version of this article (doi:10.1186/s13613-015-0061-0) contains supplementary material, which is available to authorized users.
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              The Differential Effect of Toxoplasma Gondii Infection on the Stability of BCL2-Family Members Involves Multiple Activities

              The regulation of mitochondrial permeability, a key event in the initiation of apoptosis is governed by the opposing actions of the pro- and anti-apoptotic members of the BCL2-family of proteins. The BCL2-family can be classified further based on the number of BCL-homology (BH) domains they encode. Pathogen mediated modulation of BCL2-family members play a significant role in their ability to affect the apoptotic pathways in the infected host cell. The protozoan parasite Toxoplasma gondii establishes a profound blockade of apoptosis noted by a requirement for host NFκB activity and correlating with the selective degradation of pro-apoptotic BCL2-family members. In this study, we explore the potential activities associated with the inherent stability of the anti-apoptotic BCL2 as well as the selective degradation of the pro-apoptotic proteins BAX, BAD, and BID. We find that multiple activities govern the relative stability of BCL2-family members suggesting a complex and balanced network of stability-enhancing and–destabilizing activities are perturbed by parasite infection. The data leave open the possibility for both parasite induced host activities as well as the direct consequence of parasite effectors in governing the relative levels of BCL2-proteins in the course of infection.
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                Author and article information

                Journal
                Microb Drug Resist
                Microb Drug Resist
                mdr
                Microbial Drug Resistance
                Mary Ann Liebert, Inc., publishers (140 Huguenot Street, 3rd Floor New Rochelle, NY 10801 USA )
                1076-6294
                1931-8448
                January 2022
                13 January 2022
                13 January 2022
                : 28
                : 1
                : 31-38
                Affiliations
                [ 1 ]Department of Biomedical Science and Technology, School of Biological and Physical Science, Maseno University, Maseno, Kenya.
                [ 2 ]Department of Emerging Infectious Diseases, United States Army Medical Research Directorate-Africa, Kenya/Kenya Medical Research Institute, Nairobi, Kenya.
                Author notes

                Correction added on January 12, 2022 after first online publication of July 23, 2021: The article reflects Open Access, with copyright transferring to the author(s), and a Creative Commons License (CC-BY) added ( http://creativecommons.org/licenses/by/4.0).

                [*]Address correspondence to: Lillian Musila, PhD, Department of Emerging Infectious Diseases, United States Army Medical Research Directorate-Africa, Kenya/Kenya Medical Research Institute, Box 606 Village Market, Nairobi 00621, Kenya lillian.musila@ 123456usamru-k.org
                Author information
                https://orcid.org/0000-0003-1418-6523
                Article
                10.1089/mdr.2020.0432
                10.1089/mdr.2020.0432
                8792489
                34297634
                3a743876-3154-4b21-a8bc-af570d478333
                © Catherine Wawira Muriuki et al. 2022; Published by Mary Ann Liebert, Inc.

                This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 2, Tables: 3, References: 35, Pages: 8
                Categories
                Epidemiology

                phenotypic,genotypic,esbl,pampc,uropathogenic escherichia coli (upec),antimicrobial resistance,urinary tract infections

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