bla(CTX-M-152), a Novel Variant of CTX-M-group-25, Identified in a Study Performed on the Prevalence of Multidrug Resistance among Natural Inhabitants of River Yamuna, India

Natural environment influenced by anthropogenic activities creates selective pressure for acquisition and spread of resistance genes. In this study, we determined the prevalence of Extended Spectrum β-Lactamases producing gram negative bacteria from the River Yamuna, India, and report the identifica...

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Autores principales: Azam, Mudsser, Jan, Arif T., Haq, Qazi M. R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762991/
https://www.ncbi.nlm.nih.gov/pubmed/26941715
http://dx.doi.org/10.3389/fmicb.2016.00176
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author Azam, Mudsser
Jan, Arif T.
Haq, Qazi M. R.
author_facet Azam, Mudsser
Jan, Arif T.
Haq, Qazi M. R.
author_sort Azam, Mudsser
collection PubMed
description Natural environment influenced by anthropogenic activities creates selective pressure for acquisition and spread of resistance genes. In this study, we determined the prevalence of Extended Spectrum β-Lactamases producing gram negative bacteria from the River Yamuna, India, and report the identification and characterization of a novel CTX-M gene variant bla(CTX-M-152). Of the total 230 non-duplicate isolates obtained from collected water samples, 40 isolates were found positive for ESBL production through Inhibitor-Potentiation Disc Diffusion test. Based on their resistance profile, 3% were found exhibiting pandrug resistance (PDR), 47% extensively drug resistance (XDR), and remaining 50% showing multidrug resistant (MDR). Following screening and antimicrobial profiling, characterization of ESBLs (bla(TEM) and bla(CTX-M)), and mercury tolerance determinants (merP, merT, and merB) were performed. In addition to abundance of bla(TEM-116) (57.5%) and bla(CTX-M-15) (37.5%), bacteria were also found to harbor other variants of ESBLs like bla(CTX-M-71) (5%), bla(CTX-M-3) (7.5%), bla(CTX-M-32) (2.5%), bla(CTX-M-152) (7.5%), bla(CTX-M-55) (2.5%), along with some non-ESBLs; bla(TEM-1) (25%) and bla(OXY) (5%). Additionally, co-occurrence of mercury tolerance genes were observed among 40% of isolates. In silico studies of the new variant, bla(CTX-M-152)were conducted through modeling for the generation of structure followed by docking to determine its catalytic profile. CTX-M-152 was found to be an out-member of CTX-M-group-25 due to Q26H, T154A, G89D, P99S, and D146G substitutions. Five residues Ser70, Asn132, Ser237, Gly238, and Arg273 were found responsible for positioning of cefotaxime into the active site through seven H-bonds with binding energy of -7.6 Kcal/mol. Despite small active site, co-operative interactions of Ser237 and Arg276 were found actively contributing to its high catalytic efficiency. To the best of our knowledge, this is the first report of bla(CTX-M-152) of CTX-M-group-25 from Indian subcontinent. Taking a note of bacteria harboring such high proportion of multidrug and mercury resistance determinants, their presence in natural water resources employed for human consumption increases the chances of potential risk to human health. Hence, deeper insights into mechanisms pertaining to resistance development are required to frame out strategies to tackle the situation and prevent acquisition and dissemination of resistance determinants so as to combat the escalating burden of infectious diseases.
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spelling pubmed-47629912016-03-03 bla(CTX-M-152), a Novel Variant of CTX-M-group-25, Identified in a Study Performed on the Prevalence of Multidrug Resistance among Natural Inhabitants of River Yamuna, India Azam, Mudsser Jan, Arif T. Haq, Qazi M. R. Front Microbiol Microbiology Natural environment influenced by anthropogenic activities creates selective pressure for acquisition and spread of resistance genes. In this study, we determined the prevalence of Extended Spectrum β-Lactamases producing gram negative bacteria from the River Yamuna, India, and report the identification and characterization of a novel CTX-M gene variant bla(CTX-M-152). Of the total 230 non-duplicate isolates obtained from collected water samples, 40 isolates were found positive for ESBL production through Inhibitor-Potentiation Disc Diffusion test. Based on their resistance profile, 3% were found exhibiting pandrug resistance (PDR), 47% extensively drug resistance (XDR), and remaining 50% showing multidrug resistant (MDR). Following screening and antimicrobial profiling, characterization of ESBLs (bla(TEM) and bla(CTX-M)), and mercury tolerance determinants (merP, merT, and merB) were performed. In addition to abundance of bla(TEM-116) (57.5%) and bla(CTX-M-15) (37.5%), bacteria were also found to harbor other variants of ESBLs like bla(CTX-M-71) (5%), bla(CTX-M-3) (7.5%), bla(CTX-M-32) (2.5%), bla(CTX-M-152) (7.5%), bla(CTX-M-55) (2.5%), along with some non-ESBLs; bla(TEM-1) (25%) and bla(OXY) (5%). Additionally, co-occurrence of mercury tolerance genes were observed among 40% of isolates. In silico studies of the new variant, bla(CTX-M-152)were conducted through modeling for the generation of structure followed by docking to determine its catalytic profile. CTX-M-152 was found to be an out-member of CTX-M-group-25 due to Q26H, T154A, G89D, P99S, and D146G substitutions. Five residues Ser70, Asn132, Ser237, Gly238, and Arg273 were found responsible for positioning of cefotaxime into the active site through seven H-bonds with binding energy of -7.6 Kcal/mol. Despite small active site, co-operative interactions of Ser237 and Arg276 were found actively contributing to its high catalytic efficiency. To the best of our knowledge, this is the first report of bla(CTX-M-152) of CTX-M-group-25 from Indian subcontinent. Taking a note of bacteria harboring such high proportion of multidrug and mercury resistance determinants, their presence in natural water resources employed for human consumption increases the chances of potential risk to human health. Hence, deeper insights into mechanisms pertaining to resistance development are required to frame out strategies to tackle the situation and prevent acquisition and dissemination of resistance determinants so as to combat the escalating burden of infectious diseases. Frontiers Media S.A. 2016-02-23 /pmc/articles/PMC4762991/ /pubmed/26941715 http://dx.doi.org/10.3389/fmicb.2016.00176 Text en Copyright © 2016 Azam, Jan and Haq. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Microbiology
Azam, Mudsser
Jan, Arif T.
Haq, Qazi M. R.
bla(CTX-M-152), a Novel Variant of CTX-M-group-25, Identified in a Study Performed on the Prevalence of Multidrug Resistance among Natural Inhabitants of River Yamuna, India
title bla(CTX-M-152), a Novel Variant of CTX-M-group-25, Identified in a Study Performed on the Prevalence of Multidrug Resistance among Natural Inhabitants of River Yamuna, India
title_full bla(CTX-M-152), a Novel Variant of CTX-M-group-25, Identified in a Study Performed on the Prevalence of Multidrug Resistance among Natural Inhabitants of River Yamuna, India
title_fullStr bla(CTX-M-152), a Novel Variant of CTX-M-group-25, Identified in a Study Performed on the Prevalence of Multidrug Resistance among Natural Inhabitants of River Yamuna, India
title_full_unstemmed bla(CTX-M-152), a Novel Variant of CTX-M-group-25, Identified in a Study Performed on the Prevalence of Multidrug Resistance among Natural Inhabitants of River Yamuna, India
title_short bla(CTX-M-152), a Novel Variant of CTX-M-group-25, Identified in a Study Performed on the Prevalence of Multidrug Resistance among Natural Inhabitants of River Yamuna, India
title_sort bla(ctx-m-152), a novel variant of ctx-m-group-25, identified in a study performed on the prevalence of multidrug resistance among natural inhabitants of river yamuna, india
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762991/
https://www.ncbi.nlm.nih.gov/pubmed/26941715
http://dx.doi.org/10.3389/fmicb.2016.00176
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