Genomic insight into mechanisms of reversion of antibiotic resistance in multidrug resistant Mycobacterium tuberculosis induced by a nanomolecular iodine-containing complex FS-1

Show simple item record llin, Aleksandr l. Kulmanov, Murat E. Korotetskiy, llya S. Islamov, Rinat A. Akhmetova, Gulshara K. Lankina, Marina V. Reva, Oleg N. 2017-08-14T07:40:21Z 2017-08-14T07:40:21Z 2017-05-08
dc.description.abstract Drug induced reversion of antibiotic resistance is a promising way to combat multidrug resistant infections. However, lacking knowledge of mechanisms of drug resistance reversion impedes employing this approach in medicinal therapies. Induction of antibiotic resistance reversion by a new anti-tuberculosis drug FS-1 has been reported. FS-1 was used in this work in combination with standard anti-tuberculosis antibiotics in an experiment on laboratory guinea pigs infected with an extensively drug resistant (XDR) strain Mycobacterium tuberculosis SCAID 187.0. During the experimental trial, genetic changes in the population were analyzed by sequencing of M. tuberculosis isolates followed by variant calling. In total 11 isolates obtained from different groups of infected animals at different stages of disease development and treatment were sequenced. It was found that despite the selective pressure of antibiotics, FS-1 caused a counter-selection of drug resistant variants that speeded up the recovery of the infected animals from XDR tuberculosis. Drug resistance mutations reported in the genome of the initial strain remained intact in more sensitive isolates obtained in this experiment. Variant calling in the sequenced genomes revealed that the drug resistance reversion could be associated with a general increase in genetic heterogeneity of the population of M. tuberculosis. Accumulation of mutations in PpsA and PpsE subunits of phenolpthiocerol polyketide synthase was observed in the isolates treated with FS-1 that may indicate an increase of persisting variants in the population. It was hypothesized that FS-1 caused an active counter-selection of drug resistant variants from the population by aggravating the cumulated fitness cost of the drug resistance mutations. Action of FS-1 on drug resistant bacteria exemplified the theoretically predicted induced synergy mechanism of drug resistance reversion. An experimental model to study the drug resistance reversion phenomenon is hereby introduced en_ZA
dc.description.department Biochemistry en_ZA
dc.description.librarian am2017 en_ZA
dc.description.sponsorship The research was funded by the grant 0115PK00389 provided by the Ministry for investments and development of Kazakhstan. Bioinformatic analysis was funded by the grant #93664 provided for ONR by the National Research Foundation (NRF) of South Africa. en_ZA
dc.description.uri en_ZA
dc.identifier.citation Ilin AI, Kulmanov ME, Korotetskiy IS, Islamov RA, Akhmetova GK, Lankina MV and Reva ON (2017) Genomic Insight into Mechanisms of Reversion of Antibiotic Resistance in Multidrug Resistant Mycobacterium tuberculosis Induced by a Nanomolecular Iodine-Containing Complex FS-1. Front. Cell. Infect. Microbiol. 7:151. DOI: 10.3389/fcimb.2017.00151. en_ZA
dc.identifier.issn 2235-2988 (online)
dc.identifier.other 10.3389/fcimb.2017.00151
dc.language.iso en en_ZA
dc.publisher Frontiers Research Foundation en_ZA
dc.rights © 2017 Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). en_ZA
dc.subject Drug resistance reversion en_ZA
dc.subject New drug en_ZA
dc.subject Next generation sequencing (NGS) en_ZA
dc.subject Mycobacterium tuberculosis (MTB) en_ZA
dc.subject Extensively drug resistant (XDR) en_ZA
dc.title Genomic insight into mechanisms of reversion of antibiotic resistance in multidrug resistant Mycobacterium tuberculosis induced by a nanomolecular iodine-containing complex FS-1 en_ZA
dc.type Article en_ZA

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