Growth-Phase-Dependent Modulation of Quorum Sensing and Virulence Factors in <i>Pseudomonas aeruginosa</i> ATCC 27853 by Sub-MICs of Antibiotics
<b>Background</b>: Antibiotics at sub-inhibitory concentrations can rewire bacterial regulatory networks, impacting virulence. <b>Objective</b>: The way that exposure to selected antibiotics (ciprofloxacin, amikacin, azithromycin, ceftazidime, and meropenem) below their minim...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/14/7/731 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850077485066092544 |
|---|---|
| author | Ahmed Noby Amer Nancy Attia Daniel Baecker Rasha Emad Mansour Ingy El-Soudany |
| author_facet | Ahmed Noby Amer Nancy Attia Daniel Baecker Rasha Emad Mansour Ingy El-Soudany |
| author_sort | Ahmed Noby Amer |
| collection | DOAJ |
| description | <b>Background</b>: Antibiotics at sub-inhibitory concentrations can rewire bacterial regulatory networks, impacting virulence. <b>Objective</b>: The way that exposure to selected antibiotics (ciprofloxacin, amikacin, azithromycin, ceftazidime, and meropenem) below their minimum inhibitory concentration (sub-MIC) modulates the physiology of <i>Pseudomonas aeruginosa</i> is examined in this study using growth-phase-resolved analysis. <b>Methods</b>: Standard <i>P. aeruginosa</i> strain cultures were exposed to ¼ and ½ MIC to determine the growth kinetics under antibiotic stress. The study measured protease and pyocyanin production and the expression level of important quorum sensing and virulence genes (<i>lasI</i>/<i>R</i>, <i>rhlI</i>/<i>R</i>, <i>pqsR</i>/<i>A</i>, and <i>phzA</i>) at different growth phases. <b>Results</b>: Meropenem produced the most noticeable growth suppression at ½ MIC. Sub-MIC antibiotics did not completely stop growth, but caused distinct, dose-dependent changes. Azithromycin eliminated protease activity in all phases and had a biphasic effect on pyocyanin. Ciprofloxacin consistently inhibited both pyocyanin and protease in all phases. The effects of amikacin varied by phase and dose, while β-lactams markedly increased pyocyanin production during the log phase. In contrast to the plateau phase, when expression was often downregulated or unchanged, most quorum-sensing- and virulence-associated genes showed significant upregulation during the death phase under sub-MIC exposure. <b>Conclusions</b>: These findings indicate that sub-MIC antibiotics act as biochemical signal modulators, preserving stress-adapted sub-populations that, in late growth phases, activate quorum sensing and stress tolerance pathways. |
| format | Article |
| id | doaj-art-e718964e0cf24f60b7dafc8708006d17 |
| institution | DOAJ |
| issn | 2079-6382 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj-art-e718964e0cf24f60b7dafc8708006d172025-08-20T02:45:48ZengMDPI AGAntibiotics2079-63822025-07-0114773110.3390/antibiotics14070731Growth-Phase-Dependent Modulation of Quorum Sensing and Virulence Factors in <i>Pseudomonas aeruginosa</i> ATCC 27853 by Sub-MICs of AntibioticsAhmed Noby Amer0Nancy Attia1Daniel Baecker2Rasha Emad Mansour3Ingy El-Soudany4Microbiology and Immunology Department, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria 21648, EgyptMicrobiology Department, Medical Research Institute, Alexandria University, Alexandria 26571, EgyptDepartment of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2+4, 14195 Berlin, GermanyAlexandria Main University Hospital, Alexandria 21526, EgyptMicrobiology and Immunology Department, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria 21648, Egypt<b>Background</b>: Antibiotics at sub-inhibitory concentrations can rewire bacterial regulatory networks, impacting virulence. <b>Objective</b>: The way that exposure to selected antibiotics (ciprofloxacin, amikacin, azithromycin, ceftazidime, and meropenem) below their minimum inhibitory concentration (sub-MIC) modulates the physiology of <i>Pseudomonas aeruginosa</i> is examined in this study using growth-phase-resolved analysis. <b>Methods</b>: Standard <i>P. aeruginosa</i> strain cultures were exposed to ¼ and ½ MIC to determine the growth kinetics under antibiotic stress. The study measured protease and pyocyanin production and the expression level of important quorum sensing and virulence genes (<i>lasI</i>/<i>R</i>, <i>rhlI</i>/<i>R</i>, <i>pqsR</i>/<i>A</i>, and <i>phzA</i>) at different growth phases. <b>Results</b>: Meropenem produced the most noticeable growth suppression at ½ MIC. Sub-MIC antibiotics did not completely stop growth, but caused distinct, dose-dependent changes. Azithromycin eliminated protease activity in all phases and had a biphasic effect on pyocyanin. Ciprofloxacin consistently inhibited both pyocyanin and protease in all phases. The effects of amikacin varied by phase and dose, while β-lactams markedly increased pyocyanin production during the log phase. In contrast to the plateau phase, when expression was often downregulated or unchanged, most quorum-sensing- and virulence-associated genes showed significant upregulation during the death phase under sub-MIC exposure. <b>Conclusions</b>: These findings indicate that sub-MIC antibiotics act as biochemical signal modulators, preserving stress-adapted sub-populations that, in late growth phases, activate quorum sensing and stress tolerance pathways.https://www.mdpi.com/2079-6382/14/7/731quorum sensingsub-MICgrowth phases<i>Pseudomonas aeruginosa</i>ciprofloxacinamikacin |
| spellingShingle | Ahmed Noby Amer Nancy Attia Daniel Baecker Rasha Emad Mansour Ingy El-Soudany Growth-Phase-Dependent Modulation of Quorum Sensing and Virulence Factors in <i>Pseudomonas aeruginosa</i> ATCC 27853 by Sub-MICs of Antibiotics Antibiotics quorum sensing sub-MIC growth phases <i>Pseudomonas aeruginosa</i> ciprofloxacin amikacin |
| title | Growth-Phase-Dependent Modulation of Quorum Sensing and Virulence Factors in <i>Pseudomonas aeruginosa</i> ATCC 27853 by Sub-MICs of Antibiotics |
| title_full | Growth-Phase-Dependent Modulation of Quorum Sensing and Virulence Factors in <i>Pseudomonas aeruginosa</i> ATCC 27853 by Sub-MICs of Antibiotics |
| title_fullStr | Growth-Phase-Dependent Modulation of Quorum Sensing and Virulence Factors in <i>Pseudomonas aeruginosa</i> ATCC 27853 by Sub-MICs of Antibiotics |
| title_full_unstemmed | Growth-Phase-Dependent Modulation of Quorum Sensing and Virulence Factors in <i>Pseudomonas aeruginosa</i> ATCC 27853 by Sub-MICs of Antibiotics |
| title_short | Growth-Phase-Dependent Modulation of Quorum Sensing and Virulence Factors in <i>Pseudomonas aeruginosa</i> ATCC 27853 by Sub-MICs of Antibiotics |
| title_sort | growth phase dependent modulation of quorum sensing and virulence factors in i pseudomonas aeruginosa i atcc 27853 by sub mics of antibiotics |
| topic | quorum sensing sub-MIC growth phases <i>Pseudomonas aeruginosa</i> ciprofloxacin amikacin |
| url | https://www.mdpi.com/2079-6382/14/7/731 |
| work_keys_str_mv | AT ahmednobyamer growthphasedependentmodulationofquorumsensingandvirulencefactorsinipseudomonasaeruginosaiatcc27853bysubmicsofantibiotics AT nancyattia growthphasedependentmodulationofquorumsensingandvirulencefactorsinipseudomonasaeruginosaiatcc27853bysubmicsofantibiotics AT danielbaecker growthphasedependentmodulationofquorumsensingandvirulencefactorsinipseudomonasaeruginosaiatcc27853bysubmicsofantibiotics AT rashaemadmansour growthphasedependentmodulationofquorumsensingandvirulencefactorsinipseudomonasaeruginosaiatcc27853bysubmicsofantibiotics AT ingyelsoudany growthphasedependentmodulationofquorumsensingandvirulencefactorsinipseudomonasaeruginosaiatcc27853bysubmicsofantibiotics |