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Molecular profiling of multidrug-resistant river water isolates: insights into resistance mechanism and potential inhibitors
Microbial Diversity Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Pune, India.
Bioinformatics Research Laboratory, Pune, India.
Biotechnology and Bioinformatics Institute, Pune, India.
Biotechnology and Bioinformatics Institute, Pune, India.
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2020 (English)In: Environmental Science and Pollution Research, ISSN 0944-1344, E-ISSN 1614-7499, Vol. 27, no 22, p. 27279-27292Article in journal (Refereed) Published
Abstract [en]

Polluted waters are an important reservoir for antibiotic resistance genes and multidrug-resistant bacteria. This report describes the microbial community, antibiotic resistance genes, and the genetic profile of extended spectrum β-lactamase strains isolated from rivers at, Pune, India. ESBL-producing bacteria isolated from diverse river water catchments running through Pune City were characterized for their antibiotic resistance. The microbial community and types of genes which confer antibiotic resistance were identified followed by the isolation of antibiotic-resistant bacteria on selective media and their genome analysis. Four representative isolates were sequenced using next generation sequencing for genomic analysis. They were identified as Pseudomonas aeruginosa, Escherichia coli, and two isolates were Enterobacter cloacae. The genes associated with the multidrug efflux pumps, such as tolC, macA, macB, adeL, and rosB, were detected in the isolates. As MacAB-TolC is an ABC type efflux pump responsible for conferring resistance in bacteria to several antibiotics, potential efflux pump inhibitors were identified by molecular docking. The homology model of their MacB protein with that from Escherichia coli K12 demonstrated structural changes in different motifs of MacB. Molecular docking of reported efflux pump inhibitors revealed the highest binding affinity of compound MC207-110 against MacB. It also details the potential efflux pump inhibitors that can serve as possible drug targets in drug development and discovery.

Place, publisher, year, edition, pages
Springer, 2020. Vol. 27, no 22, p. 27279-27292
Keywords [en]
Antimicrobial resistance, Efflux pump inhibitors, Extended spectrum β-lactamase, MacB, Multidrug efflux pump
National Category
Microbiology Environmental Sciences
Identifiers
URN: urn:nbn:se:oru:diva-75620DOI: 10.1007/s11356-019-05738-2ISI: 000545126100011PubMedID: 31236860Scopus ID: 2-s2.0-85068134896OAI: oai:DiVA.org:oru-75620DiVA, id: diva2:1344216
Funder
Swedish Research Council Formas, 219-2014-837Available from: 2019-08-20 Created: 2019-08-20 Last updated: 2020-08-14Bibliographically approved

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Khan, Faisal AhmadJass, Jana

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