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Substitutions in SurA and BamA Lead to Reduced Susceptibility to Broad Range Antibiotics in Gonococci

There is growing concern about the emergence and spread of multidrug-resistant Neisseria gonorrhoeae. To effectively control antibiotic-resistant bacterial pathogens, it is necessary to develop new antimicrobials and to understand the resistance mechanisms to existing antibiotics. In this study, we...

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Autores principales: Bodoev, Ivan, Malakhova, Maja, Bespyatykh, Julia, Bespiatykh, Dmitry, Arapidi, Georgij, Pobeguts, Olga, Zgoda, Victor, Shitikov, Egor, Ilina, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467665/
https://www.ncbi.nlm.nih.gov/pubmed/34573293
http://dx.doi.org/10.3390/genes12091312
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author Bodoev, Ivan
Malakhova, Maja
Bespyatykh, Julia
Bespiatykh, Dmitry
Arapidi, Georgij
Pobeguts, Olga
Zgoda, Victor
Shitikov, Egor
Ilina, Elena
author_facet Bodoev, Ivan
Malakhova, Maja
Bespyatykh, Julia
Bespiatykh, Dmitry
Arapidi, Georgij
Pobeguts, Olga
Zgoda, Victor
Shitikov, Egor
Ilina, Elena
author_sort Bodoev, Ivan
collection PubMed
description There is growing concern about the emergence and spread of multidrug-resistant Neisseria gonorrhoeae. To effectively control antibiotic-resistant bacterial pathogens, it is necessary to develop new antimicrobials and to understand the resistance mechanisms to existing antibiotics. In this study, we discovered the unexpected onset of drug resistance in N. gonorrhoeae caused by amino acid substitutions in the periplasmic chaperone SurA and the β-barrel assembly machinery component BamA. Here, we investigated the i19.05 clinical isolate with mutations in corresponding genes along with reduced susceptibility to penicillin, tetracycline, and azithromycin. The mutant strain NG05 (surA(mut) bamA(mut), and penA(mut)) was obtained using the pan-susceptible n01.08 clinical isolate as a recipient in the transformation procedure. Comparative proteomic analysis of NG05 and n01.08 strains revealed significantly increased levels of other chaperones, Skp and FkpA, and some transport proteins. Efflux pump inhibition experiments demonstrated that the reduction in sensitivity was achieved due to the activity of efflux pumps. We hypothesize that the described mutations in the surA and bamA genes cause the qualitative and quantitative changes of periplasmic chaperones, which in turn alters the function of synthesized cell envelope proteins.
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spelling pubmed-84676652021-09-27 Substitutions in SurA and BamA Lead to Reduced Susceptibility to Broad Range Antibiotics in Gonococci Bodoev, Ivan Malakhova, Maja Bespyatykh, Julia Bespiatykh, Dmitry Arapidi, Georgij Pobeguts, Olga Zgoda, Victor Shitikov, Egor Ilina, Elena Genes (Basel) Article There is growing concern about the emergence and spread of multidrug-resistant Neisseria gonorrhoeae. To effectively control antibiotic-resistant bacterial pathogens, it is necessary to develop new antimicrobials and to understand the resistance mechanisms to existing antibiotics. In this study, we discovered the unexpected onset of drug resistance in N. gonorrhoeae caused by amino acid substitutions in the periplasmic chaperone SurA and the β-barrel assembly machinery component BamA. Here, we investigated the i19.05 clinical isolate with mutations in corresponding genes along with reduced susceptibility to penicillin, tetracycline, and azithromycin. The mutant strain NG05 (surA(mut) bamA(mut), and penA(mut)) was obtained using the pan-susceptible n01.08 clinical isolate as a recipient in the transformation procedure. Comparative proteomic analysis of NG05 and n01.08 strains revealed significantly increased levels of other chaperones, Skp and FkpA, and some transport proteins. Efflux pump inhibition experiments demonstrated that the reduction in sensitivity was achieved due to the activity of efflux pumps. We hypothesize that the described mutations in the surA and bamA genes cause the qualitative and quantitative changes of periplasmic chaperones, which in turn alters the function of synthesized cell envelope proteins. MDPI 2021-08-25 /pmc/articles/PMC8467665/ /pubmed/34573293 http://dx.doi.org/10.3390/genes12091312 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bodoev, Ivan
Malakhova, Maja
Bespyatykh, Julia
Bespiatykh, Dmitry
Arapidi, Georgij
Pobeguts, Olga
Zgoda, Victor
Shitikov, Egor
Ilina, Elena
Substitutions in SurA and BamA Lead to Reduced Susceptibility to Broad Range Antibiotics in Gonococci
title Substitutions in SurA and BamA Lead to Reduced Susceptibility to Broad Range Antibiotics in Gonococci
title_full Substitutions in SurA and BamA Lead to Reduced Susceptibility to Broad Range Antibiotics in Gonococci
title_fullStr Substitutions in SurA and BamA Lead to Reduced Susceptibility to Broad Range Antibiotics in Gonococci
title_full_unstemmed Substitutions in SurA and BamA Lead to Reduced Susceptibility to Broad Range Antibiotics in Gonococci
title_short Substitutions in SurA and BamA Lead to Reduced Susceptibility to Broad Range Antibiotics in Gonococci
title_sort substitutions in sura and bama lead to reduced susceptibility to broad range antibiotics in gonococci
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467665/
https://www.ncbi.nlm.nih.gov/pubmed/34573293
http://dx.doi.org/10.3390/genes12091312
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