Publication:
Resensitization to colistin results in rapid and stable recovery of adherence, serum resistance and ompW in Acinetobacter baumannii

dc.contributor.coauthorMenekşe, Şirin
dc.contributor.departmentDepartment of Industrial Engineering
dc.contributor.departmentGraduate School of Health Sciences
dc.contributor.departmentKUH (Koç University Hospital)
dc.contributor.departmentKUIS AI (Koç University & İş Bank Artificial Intelligence Center)
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorBoral, Jale
dc.contributor.kuauthorCan, Füsun
dc.contributor.kuauthorGönen, Mehmet
dc.contributor.kuauthorKeske, Şiran
dc.contributor.kuauthorÖzcan, Gülin
dc.contributor.kuauthorVatansever, Cansel
dc.contributor.schoolcollegeinstituteCollege of Engineering
dc.contributor.schoolcollegeinstituteGRADUATE SCHOOL OF HEALTH SCIENCES
dc.contributor.schoolcollegeinstituteKUH (KOÇ UNIVERSITY HOSPITAL)
dc.contributor.schoolcollegeinstituteResearch Center
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-12-29T09:39:29Z
dc.date.issued2024
dc.description.abstractBackground Colistin resistance in Acinetobacter baumannii is an emerging problem that limits antimicrobial therapy options. Materials & methods We isolated two pairs of colistin susceptible and colistin-resistant A. baumannii (K1007/ K1006 and K408/K409) from two patients diagnosed with carbapenem-resistant A. baumannii infection. Colistin susceptible isolates were exposed to in vitro colistin induction for 50 generations. The selected cell populations were subjected to DNA and RNA sequencing and phenotypic assays. Results In the in vitro induction assay, K408 gained colistin resistance on the corresponding day of clinical resistance (K408-G25) and got resensitized to colistin in the consecutive generation (K408-G26). A significant upregulation of ompW, ata, adeFGH genes on K408-G25 was followed by a downregulation upon resensitization to colistin (G26). Despite the upregulation of the ompW gene in transcriptomic analysis, the ompW protein disappeared on K408-G25 and recovered in the resensitized generation (G26). In parallel, disrupted cell membrane integrity recovered in K408-G26. In the K408-G25, downregulation of pbpG and upregulation of pbp1a/pbp3 genes decreased serum-resistance which was reversed in the resensitized generation (G26). The K1007 did not gain colistin resistance amongst 50-generations, however, the generation corresponding to clinical resistance day (K1007-G9) had a similar trend with K408-G25. The clinical colistin-resistant K409 and K1006 had SNPs on pmrA and pmrB genes. Conclusion In this study, we observed that A. baumannii regulates adhesion, efflux pumps and serum-resistance associated genes as an early response to colistin stress. Besides, the ompW protein disappears in the cell membrane of colistin resistant cells which recovers after resensitization to colistin. The lack of ompW protein in colistin-resistant cells should be taken into consideration for escape mutants in development of antivirulence vaccination or treatment options. © 2024 Public Library of Science. All rights reserved.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue8
dc.description.openaccessGold Open Access
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuTÜBİTAK
dc.description.sponsorshipThis study was funded by the Scientific and Technological Research Council of Turkey (TUBITAK) under the project number of 119S446 to the corresponding author Fusun Can. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.description.volume19
dc.identifier.doi10.1371/journal.pone.0309307
dc.identifier.issn1932-6203
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85202672388
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0309307
dc.identifier.urihttps://hdl.handle.net/20.500.14288/23003
dc.identifier.wos1305462200031
dc.keywordsAcinetobacter baumannii
dc.keywordsAcinetobacter infections
dc.keywordsAnti-bacterial agents
dc.keywordsBacterial adhesion
dc.keywordsBacterial outer membrane Proteins
dc.keywordscarbapenems
dc.keywordsColistin
dc.keywordsDrug resistance, Bacterial
dc.keywordsGene expression Regulation, Bacterial
dc.keywordsHumans
dc.keywordsMicrobial sensitivity tests
dc.language.isoeng
dc.publisherPublic Library of Science
dc.relation.grantno119S446
dc.relation.ispartofPublic Library of Science
dc.subjectResistance and antimicrobials
dc.titleResensitization to colistin results in rapid and stable recovery of adherence, serum resistance and ompW in Acinetobacter baumannii
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorBoral, Jale
local.contributor.kuauthorVatansever, Cansel
local.contributor.kuauthorÖzcan, Gülin
local.contributor.kuauthorKeske, Şiran
local.contributor.kuauthorGönen, Mehmet
local.contributor.kuauthorCan, Füsun
local.publication.orgunit1College of Engineering
local.publication.orgunit1GRADUATE SCHOOL OF HEALTH SCIENCES
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit1Research Center
local.publication.orgunit1KUH (KOÇ UNIVERSITY HOSPITAL)
local.publication.orgunit2Department of Industrial Engineering
local.publication.orgunit2KUIS AI (Koç University & İş Bank Artificial Intelligence Center)
local.publication.orgunit2KUH (Koç University Hospital)
local.publication.orgunit2School of Medicine
local.publication.orgunit2Graduate School of Health Sciences
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