{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:33:09Z","timestamp":1792459989051,"version":"4.5.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                      is a formidable pathogen renowned for its role in hospital-acquired infections. In recent years, largely due to antibiotic abuse and other reasons, bacteria are frequently exposed to sub-minimum inhibitory concentration (sub-MIC) levels of antibiotics. Accumulating evidence suggests that sub-MIC antibiotic pressure serves as a critical driver of bacterial resistance evolution and virulence adaptation. However, the regulatory mechanisms underlying antibiotic stress adaptation in\n                      <jats:italic>A. baumannii<\/jats:italic>\n                      remains poorly understood. The quorum sensing (QS) system is a key bacterial signaling network that senses population density and coordinates vital physiological functions and environmental adaptations. Targeting QS system to attenuate virulence and resistance represents a promising strategy for combating multi-drug-resistant infections. Nevertheless, the role of systems in regulating antibiotic stress response in\n                      <jats:italic>A. baumannii<\/jats:italic>\n                      has not been elucidated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we used the wild-type (WT) strain of\n                      <jats:italic>A. baumannii<\/jats:italic>\n                      and an isogenic\n                      <jats:italic>abaI<\/jats:italic>\n                      deletion mutant strain (\u0394\n                      <jats:italic>abaI<\/jats:italic>\n                      ) to investigate the involvement of QS in adaptive responses under meropenem sub-MIC pressure. The analysis was performed by phenotypic experiments such as bacterial biofilm formation and motility detection, transcriptome sequencing (RNA-seq) and qRT-PCR verification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that under antibiotic pressure, the WT strain developed significantly enhanced resistance, accompanied by increased biofilm formation, surface motility, adherence to and invasion of A549 cells, and pathogenicity in\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      . In contrast, the \u0394\n                      <jats:italic>abaI<\/jats:italic>\n                      strain showed no significant changes in resistance, motility, host cell adhesion and invasion, or virulence, with all these parameters remaining substantially lower than those of the antibiotic-treated WT. Interestingly, biofilm formation was still significantly enhanced in the \u0394\n                      <jats:italic>abaI<\/jats:italic>\n                      strain, suggesting compensatory activation of alternative regulatory mechanisms. Transcriptomic analysis revealed that sub-MIC meropenem triggered extensive gene expression changes in both the WT and \u0394\n                      <jats:italic>abaI<\/jats:italic>\n                      strains. In the WT, differentially expressed genes were enriched in pathways including quorum sensing, biofilm formation, ABC transporters, and two-component systems. In contrast, the \u0394\n                      <jats:italic>abaI<\/jats:italic>\n                      mutant exhibited distinct transcriptional profiles, with enrichment in \u0394-lactam resistance, aromatic amino acid biosynthesis, and metabolite transport. The expression trends of key virulence- and resistance-associated genes were further validated by qRT-PCR, confirming the reliability of the RNA-seq data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our study underscores the potential of targeting the QS system to mitigate antibiotic-driven adaptation and provides a strategic basis for controlling multidrug-resistant\n                      <jats:italic>A. baumannii<\/jats:italic>\n                      infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1744356","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T06:41:50Z","timestamp":1769668910000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Regulation of drug resistance and virulence of Acinetobacter baumannii by quorum sensing system under antibiotic pressure"],"prefix":"10.3389","volume":"17","author":[{"given":"Xingyu","family":"Jiang","sequence":"first","affiliation":[{"name":"The Key Laboratory of Zoonosis, Department of Pathogen Biology, Chinese Ministry of Education, College of Basic Medical Sciences, Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuchun","family":"Shan","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Zoonosis, Department of Pathogen Biology, Chinese Ministry of Education, College of Basic Medical Sciences, Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Yang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Zoonosis, Department of Pathogen Biology, Chinese Ministry of Education, College of Basic Medical Sciences, Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Zoonosis, Department of Pathogen Biology, Chinese Ministry of Education, College of Basic Medical Sciences, Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xiang","sequence":"additional","affiliation":[{"name":"The First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Ni","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Zoonosis, Department of Pathogen Biology, Chinese Ministry of Education, College of Basic Medical Sciences, Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/nrmicro3270","article-title":"Microbiological effects of sublethal levels of antibiotics","volume":"12","author":"Andersson","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1111\/2049-632X.12125","article-title":"Acinetobacter baumannii: evolution of a global pathogen","volume":"71","author":"Antunes","year":"2014","journal-title":"Pathog. Dis."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"3531","DOI":"10.1038\/s41467-023-39316-5","article-title":"A polyamine acetyltransferase regulates the motility and biofilm formation of Acinetobacter baumannii","volume":"14","author":"Armalyte","year":"2023","journal-title":"Nat. Commun."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1196774","DOI":"10.3389\/fmicb.2023.1196774","article-title":"Acinetobacter baumannii in the critically ill: complex infections get complicated","volume":"14","author":"Cavallo","year":"2023","journal-title":"Front. Microbiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.jare.2021.01.008","article-title":"Virulence alterations in staphylococcus aureus upon treatment with the sub-inhibitory concentrations of antibiotics","volume":"31","author":"Chen","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1186\/1471-2180-8-216","article-title":"Acinetobacter baumannii invades epithelial cells and outer membrane protein a mediates interactions with epithelial cells","volume":"8","author":"Choi","year":"2008","journal-title":"BMC Microbiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2201","DOI":"10.1080\/21505594.2021.1950268","article-title":"Importance of twitching and surface-associated motility in the virulence of Acinetobacter baumannii","volume":"12","author":"Corral","year":"2021","journal-title":"Virulence"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1093\/jac\/dkn322","article-title":"Subinhibitory concentrations of penicillin increase the mutation rate to optochin resistance in Streptococcus pneumoniae","volume":"62","author":"Cortes","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/s0924-8579(02)00391-6","article-title":"Gemifloxacin: effects of sub-inhibitory concentrations on various factors affecting bacterial virulence","volume":"21","author":"Dal Sasso","year":"2003","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"4061","DOI":"10.3892\/mmr.2017.6528","article-title":"Acinetobacter baumannii quorum-sensing signalling molecule induces the expression of drug-resistance genes","volume":"15","author":"Dou","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"8397","DOI":"10.1038\/s41467-025-63284-7","article-title":"Evolutionary loss of an antibiotic efflux pump increases Pseudomonas aeruginosa quorum sensing mediated virulence in vivo","volume":"16","author":"Fernandes","year":"2025","journal-title":"Nat. Commun."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"127915","DOI":"10.1016\/j.micres.2024.127915","article-title":"Revealing quorum-sensing networks in Pseudomonas aeruginosa infections through internal and external signals to prevent new resistance trends","volume":"289","author":"Guo","year":"2024","journal-title":"Microbiol. Res."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1038\/ncomms2607","article-title":"\u03b2-Lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity","volume":"4","author":"Gutierrez","year":"2013","journal-title":"Nat. Commun."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"3601","DOI":"10.1128\/AAC.00944-13","article-title":"A mouse model of Acinetobacter baumannii-associated pneumonia using a clinically isolated hypervirulent strain","volume":"57","author":"Harris","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"4817","DOI":"10.1128\/AAC.00877-15","article-title":"Biofilm formation caused by clinical Acinetobacter baumannii isolates is associated with overexpression of the AdeFGH efflux pump","volume":"59","author":"He","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"134568","DOI":"10.1016\/j.ijbiomac.2024.134568","article-title":"The role of AbaI quorum sensing molecule synthase in host cell inflammation induced by Acinetobacter baumannii and its effect on zebrafish infection model","volume":"278","author":"Jiang","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1111\/j.1469-0691.2005.01227.x","article-title":"Clinical impact and pathogenicity of Acinetobacter","volume":"11","author":"Joly-Guillou","year":"2005","journal-title":"Clin. Microbiol. Infect."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"13136","DOI":"10.3390\/ijms232113136","article-title":"Complementary regulation of BfmRS two-component and AbaIR quorum sensing systems to express virulence-associated genes in Acinetobacter baumannii","volume":"23","author":"Kim","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"106434","DOI":"10.1016\/j.micpath.2023.106434","article-title":"PmrAB controls virulence-associated traits and outer membrane vesicle biogenesis in Acinetobacter baumannii","volume":"185","author":"Ko","year":"2023","journal-title":"Microb. Pathog."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3389\/fcimb.2017.00055","article-title":"Biology of Acinetobacter baumannii: pathogenesis, antibiotic resistance mechanisms, and prospective treatment options","volume":"7","author":"Lee","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"5697","DOI":"10.2147\/IDR.S417751","article-title":"Glabridin functions as a quorum sensing inhibitor to inhibit biofilm formation and swarming motility of multidrug-resistant Acinetobacter baumannii","volume":"16","author":"Lin","year":"2023","journal-title":"Infect. Drug Resist."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1111\/j.1574-6976.2012.00344.x","article-title":"Acinetobacter baumannii: human infections, factors contributing to pathogenesis and animal models","volume":"37","author":"McConnell","year":"2013","journal-title":"FEMS Microbiol. Rev."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"782733","DOI":"10.3389\/fcimb.2021.782733","article-title":"Galleria mellonella as a suitable model of bacterial infection: past, present and future","volume":"11","author":"Menard","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1007\/s13258-020-01005-8","article-title":"AbaR is a LuxR type regulator essential for motility and the formation of biofilm and pellicle in Acinetobacter baumannii","volume":"42","author":"Oh","year":"2020","journal-title":"Genes Genomics"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/nrmicro.2016.89","article-title":"Quorum sensing signal-response systems in gram-negative bacteria","volume":"14","author":"Papenfort","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"21521","DOI":"10.1038\/s41598-024-72740-1","article-title":"Impact of AbaI mutation on virulence, biofilm development, and antibiotic susceptibility in Acinetobacter baumannii","volume":"14","author":"Pumirat","year":"2024","journal-title":"Sci. Rep."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"2499","DOI":"10.1111\/1462-2920.14637","article-title":"Environmental potassium regulates bacterial flotation, antibiotic production and turgor pressure in Serratia through the TrkH transporter","volume":"21","author":"Quintero-Yanes","year":"2019","journal-title":"Environ. Microbiol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"113699","DOI":"10.1016\/j.jep.2020.113699","article-title":"Inhibition of biofilm and quorum sensing-regulated virulence factors in Pseudomonas aeruginosa by Cuphea carthagenensis (Jacq.) J. F. Macbr. Leaf extract: an in vitro study","volume":"269","author":"Rather","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/jam.14330","article-title":"Quorum-sensing system in Acinetobacter baumannii: a potential target for new drug development","volume":"128","author":"Saipriya","year":"2020","journal-title":"J. Appl. Microbiol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1038\/s42003-024-06645-0","article-title":"Acinetobacter baumannii OmpA-like porins: functional characterization of bacterial physiology, antibiotic-resistance, and virulence","volume":"7","author":"Scribano","year":"2024","journal-title":"Commun. Biol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1007\/s10096-020-03882-z","article-title":"Drugs with new lease of life as quorum sensing inhibitors: for combating MDR Acinetobacter baumannii infections","volume":"39","author":"Seleem","year":"2020","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1186\/s40168-023-01699-4","article-title":"Bacterial quorum sensing orchestrates longitudinal interactions to shape microbiota assembly","volume":"11","author":"Su","year":"2023","journal-title":"Microbiome"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"679241","DOI":"10.3389\/fmicb.2021.679241","article-title":"The abaI\/abaR quorum sensing system effects on pathogenicity in Acinetobacter baumannii","volume":"12","author":"Sun","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"4273","DOI":"10.2147\/IDR.S276970","article-title":"Contribution of the AbaI\/AbaR quorum sensing system to resistance and virulence of Acinetobacter baumannii clinical strains","volume":"13","author":"Tang","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1007\/s00253-024-13247-7","article-title":"Effect of L-HSL on biofilm and motility of Pseudomonas aeruginosa and its mechanism","volume":"108","author":"Tang","year":"2024","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1080\/21505594.2015.1135289","article-title":"Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing","volume":"7","author":"Tsai","year":"2016","journal-title":"Virulence"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"3","DOI":"10.4161\/gmic.28027","article-title":"Off-label abuse of antibiotics by bacteria","volume":"5","author":"Viswanathan","year":"2014","journal-title":"Gut Microbes"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"12699","DOI":"10.3390\/ijms222312699","article-title":"Inhibition of virulence factors and biofilm formation by Wogonin attenuates pathogenicity of Pseudomonas aeruginosa PAO1 via targeting pqs quorum-sensing system","volume":"22","author":"Wang","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1038\/s41564-021-00876-1","article-title":"Mucin o-glycans suppress quorum-sensing pathways and genetic transformation in Streptococcus mutans","volume":"6","author":"Werlang","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"265","DOI":"10.3389\/fmicb.2020.00265","article-title":"Anti-staphylococcus antibiotics interfere with the transcription of leucocidin ED gene in Staphylococcus aureus strain Newman","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"245","DOI":"10.3390\/antiox13020245","article-title":"Impact of reactive sulfur species on Entamoeba histolytica: modulating viability, motility, and biofilm degradation capacity","volume":"13","author":"Ye","year":"2024","journal-title":"Antioxidants (Basel)"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1744356\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T06:41:51Z","timestamp":1769668911000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1744356\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,29]]},"references-count":41,"alternative-id":["10.3389\/fmicb.2026.1744356"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1744356","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,29]]},"article-number":"1744356"}}