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Investigation of Novel pmrB and eptA Mutations in Isogenic Acinetobacter baumannii Isolates Associated with Colistin Resistance and Increased Virulence In Vivo.

dc.contributor.authorGerson, Stefanie
dc.contributor.authorBetts, Jonathan W
dc.contributor.authorLucaßen, Kai
dc.contributor.authorNodari, Carolina Silva
dc.contributor.authorWille, Julia
dc.contributor.authorJosten, Michaele
dc.contributor.authorGöttig, Stephan
dc.contributor.authorNowak, Jennifer
dc.contributor.authorStefanik, Danuta
dc.contributor.authorRoca, Ignasi
dc.contributor.authorVila, Jordi
dc.contributor.authorCisneros, Jose M
dc.contributor.authorLa-Ragione, Roberto M
dc.contributor.authorSeifert, Harald
dc.contributor.authorHiggins, Paul G
dc.date.accessioned2023-01-25T10:27:30Z
dc.date.available2023-01-25T10:27:30Z
dc.date.issued2019-02-26
dc.description.abstractColistin resistance in Acinetobacter baumannii is of great concern and is a threat to human health. In this study, we investigate the mechanisms of colistin resistance in four isogenic pairs of A. baumannii isolates displaying an increase in colistin MICs. A mutation in pmrB was detected in each colistin-resistant isolate, three of which were novel (A28V, I232T, and ΔL9-G12). Increased expression of pmrC was shown by semi-quantitative reverse transcription-PCR (qRT-PCR) for three colistin-resistant isolates, and the addition of phosphoethanolamine (PEtN) to lipid A by PmrC was revealed by mass spectrometry. Interestingly, PEtN addition was also observed in some colistin-susceptible isolates, indicating that this resistance mechanism might be strain specific and that other factors could contribute to colistin resistance. Furthermore, the introduction of pmrAB carrying the short amino acid deletion ΔL9-G12 into a pmrAB knockout strain resulted in increased pmrC expression and lipid A modification, but colistin MICs remained unchanged, further supporting the strain specificity of this colistin resistance mechanism. Of note, a mutation in the pmrC homologue eptA and a point mutation in ISAba1 upstream of eptA were associated with colistin resistance and increased eptA expression, which is a hitherto undescribed resistance mechanism. Moreover, no cost of fitness was observed for colistin-resistant isolates, while the virulence of these isolates was increased in a Galleria mellonella infection model. Although the mutations in pmrB were associated with colistin resistance, PEtN addition appears not to be the sole factor leading to colistin resistance, indicating that the mechanism of colistin resistance is far more complex than previously suspected and is potentially strain specific.
dc.description.versionSi
dc.identifier.citationGerson S, Betts JW, Lucaßen K, Nodari CS, Wille J, Josten M, et al. Investigation of Novel pmrB and eptA Mutations in Isogenic Acinetobacter baumannii Isolates Associated with Colistin Resistance and Increased Virulence In Vivo. Antimicrob Agents Chemother. 2019 Feb 26;63(3):e01586-18.
dc.identifier.doi10.1128/AAC.01586-18
dc.identifier.essn1098-6596
dc.identifier.pmcPMC6395940
dc.identifier.pmid30617096
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395940/pdf
dc.identifier.unpaywallURLhttps://europepmc.org/articles/pmc6395940?pdf=render
dc.identifier.urihttp://hdl.handle.net/10668/13385
dc.issue.number3
dc.journal.titleAntimicrobial agents and chemotherapy
dc.journal.titleabbreviationAntimicrob Agents Chemother
dc.language.isoen
dc.organizationInstituto de Biomedicina de Sevilla-IBIS
dc.organizationHospital Universitario Virgen del Rocío
dc.provenanceRealizada la curación de contenido 05/06/2025.
dc.publisherAmerican Society for Microbiology
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.relation.publisherversionhttps://journals.asm.org/doi/10.1128/AAC.01586-18?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
dc.rights.accessRightsRestricted Access
dc.subjectAcinetobacter
dc.subjectantibiotic resistance
dc.subjectgenome analysis
dc.subjectlipid A
dc.subjectvirulence
dc.subject.decsColistina
dc.subject.decsReacción en cadena de la polimerasa
dc.subject.decsInfecciones
dc.subject.decsVirulencia
dc.subject.decsAcinetobacter baumannii
dc.subject.decsMutación puntual
dc.subject.decsAminoácidos
dc.subject.meshAcinetobacter Infections
dc.subject.meshAcinetobacter baumannii
dc.subject.meshAnimals
dc.subject.meshAnti-Bacterial Agents
dc.subject.meshBacterial Proteins
dc.subject.meshColistin
dc.subject.meshDisease Models, Animal
dc.subject.meshDrug Resistance, Bacterial
dc.subject.meshHumans
dc.subject.meshLipid A
dc.subject.meshMicrobial Sensitivity Tests
dc.subject.meshMoths
dc.subject.meshTranscription Factors
dc.titleInvestigation of Novel pmrB and eptA Mutations in Isogenic Acinetobacter baumannii Isolates Associated with Colistin Resistance and Increased Virulence In Vivo.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number63
dspace.entity.typePublication

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