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Quorum sensing regulates heteroresistance in Pseudomonas aeruginosa

The prevalence and genetic mechanism of antibiotic heteroresistance (HR) have attracted significant research attention recently. However, non-genetic mechanism of HR has not been adequately explored. The present study aimed to evaluate the role of quorum sensing (QS), an important mechanism of behav...

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Autores principales: Lu, Yang, Liu, Yuyang, Zhou, Chenxu, Liu, Yaqin, Long, Yifei, Lin, Dongling, Xiong, Rui, Xiao, Qian, Huang, Bin, Chen, Cha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9650436/
https://www.ncbi.nlm.nih.gov/pubmed/36386621
http://dx.doi.org/10.3389/fmicb.2022.1017707
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author Lu, Yang
Liu, Yuyang
Zhou, Chenxu
Liu, Yaqin
Long, Yifei
Lin, Dongling
Xiong, Rui
Xiao, Qian
Huang, Bin
Chen, Cha
author_facet Lu, Yang
Liu, Yuyang
Zhou, Chenxu
Liu, Yaqin
Long, Yifei
Lin, Dongling
Xiong, Rui
Xiao, Qian
Huang, Bin
Chen, Cha
author_sort Lu, Yang
collection PubMed
description The prevalence and genetic mechanism of antibiotic heteroresistance (HR) have attracted significant research attention recently. However, non-genetic mechanism of HR has not been adequately explored. The present study aimed to evaluate the role of quorum sensing (QS), an important mechanism of behavioral coordination in different subpopulations and consequent heteroresistance. First, the prevalence of HR to 7 antibiotics was investigated in 170 clinical isolates of P. aeruginosa using population analysis profiles. The results showed that P. aeruginosa was significantly heteroresistant to meropenem (MEM), amikacin (AMK), ciprofloxacin (CIP), and ceftazidime (CAZ). The observed HR was correlated with down-regulation of QS associated genes lasI and rhlI. Further, loss-of-function analysis results showed that reduced expression of lasI and rhlI enhanced HR of P. aeruginosa to MEM, AMK, CIP, and CAZ. Conversely, overexpression of these genes or treatment with 3-oxo-C12-HSL/C4-HSL lowered HR of P. aeruginosa to the four antibiotics. Additionally, although downregulation of oprD and upregulation of efflux-associated genes was evident in heteroresistant subpopulations, their expression was not regulated by LasI and RhlI. Moreover, fitness cost measurements disclosed higher growth rates of PAO1ΔlasI and PAO1ΔrhlI in the presence of sub-MIC antibiotic as compared with that of wild-type PAO1. Our data suggest that under temporary antibiotic pressure, downregulation of QS might result in less fitness cost and promote HR of P. aeruginosa.
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spelling pubmed-96504362022-11-15 Quorum sensing regulates heteroresistance in Pseudomonas aeruginosa Lu, Yang Liu, Yuyang Zhou, Chenxu Liu, Yaqin Long, Yifei Lin, Dongling Xiong, Rui Xiao, Qian Huang, Bin Chen, Cha Front Microbiol Microbiology The prevalence and genetic mechanism of antibiotic heteroresistance (HR) have attracted significant research attention recently. However, non-genetic mechanism of HR has not been adequately explored. The present study aimed to evaluate the role of quorum sensing (QS), an important mechanism of behavioral coordination in different subpopulations and consequent heteroresistance. First, the prevalence of HR to 7 antibiotics was investigated in 170 clinical isolates of P. aeruginosa using population analysis profiles. The results showed that P. aeruginosa was significantly heteroresistant to meropenem (MEM), amikacin (AMK), ciprofloxacin (CIP), and ceftazidime (CAZ). The observed HR was correlated with down-regulation of QS associated genes lasI and rhlI. Further, loss-of-function analysis results showed that reduced expression of lasI and rhlI enhanced HR of P. aeruginosa to MEM, AMK, CIP, and CAZ. Conversely, overexpression of these genes or treatment with 3-oxo-C12-HSL/C4-HSL lowered HR of P. aeruginosa to the four antibiotics. Additionally, although downregulation of oprD and upregulation of efflux-associated genes was evident in heteroresistant subpopulations, their expression was not regulated by LasI and RhlI. Moreover, fitness cost measurements disclosed higher growth rates of PAO1ΔlasI and PAO1ΔrhlI in the presence of sub-MIC antibiotic as compared with that of wild-type PAO1. Our data suggest that under temporary antibiotic pressure, downregulation of QS might result in less fitness cost and promote HR of P. aeruginosa. Frontiers Media S.A. 2022-10-28 /pmc/articles/PMC9650436/ /pubmed/36386621 http://dx.doi.org/10.3389/fmicb.2022.1017707 Text en Copyright © 2022 Lu, Liu, Zhou, Liu, Long, Lin, Xiong, Xiao, Huang and Chen. https://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) and the copyright owner(s) 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
Lu, Yang
Liu, Yuyang
Zhou, Chenxu
Liu, Yaqin
Long, Yifei
Lin, Dongling
Xiong, Rui
Xiao, Qian
Huang, Bin
Chen, Cha
Quorum sensing regulates heteroresistance in Pseudomonas aeruginosa
title Quorum sensing regulates heteroresistance in Pseudomonas aeruginosa
title_full Quorum sensing regulates heteroresistance in Pseudomonas aeruginosa
title_fullStr Quorum sensing regulates heteroresistance in Pseudomonas aeruginosa
title_full_unstemmed Quorum sensing regulates heteroresistance in Pseudomonas aeruginosa
title_short Quorum sensing regulates heteroresistance in Pseudomonas aeruginosa
title_sort quorum sensing regulates heteroresistance in pseudomonas aeruginosa
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9650436/
https://www.ncbi.nlm.nih.gov/pubmed/36386621
http://dx.doi.org/10.3389/fmicb.2022.1017707
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