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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9650436 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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