Publication: Investigation of Novel pmrB and eptA Mutations in Isogenic Acinetobacter baumannii Isolates Associated with Colistin Resistance and Increased Virulence In Vivo.
dc.contributor.author | Gerson, Stefanie | |
dc.contributor.author | Betts, Jonathan W | |
dc.contributor.author | Lucaßen, Kai | |
dc.contributor.author | Nodari, Carolina Silva | |
dc.contributor.author | Wille, Julia | |
dc.contributor.author | Josten, Michaele | |
dc.contributor.author | Göttig, Stephan | |
dc.contributor.author | Nowak, Jennifer | |
dc.contributor.author | Stefanik, Danuta | |
dc.contributor.author | Roca, Ignasi | |
dc.contributor.author | Vila, Jordi | |
dc.contributor.author | Cisneros, Jose M | |
dc.contributor.author | La-Ragione, Roberto M | |
dc.contributor.author | Seifert, Harald | |
dc.contributor.author | Higgins, Paul G | |
dc.date.accessioned | 2023-01-25T10:27:30Z | |
dc.date.available | 2023-01-25T10:27:30Z | |
dc.date.issued | 2019-02-26 | |
dc.description.abstract | Colistin 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.version | Si | |
dc.identifier.citation | Gerson 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.doi | 10.1128/AAC.01586-18 | |
dc.identifier.essn | 1098-6596 | |
dc.identifier.pmc | PMC6395940 | |
dc.identifier.pmid | 30617096 | |
dc.identifier.pubmedURL | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395940/pdf | |
dc.identifier.unpaywallURL | https://europepmc.org/articles/pmc6395940?pdf=render | |
dc.identifier.uri | http://hdl.handle.net/10668/13385 | |
dc.issue.number | 3 | |
dc.journal.title | Antimicrobial agents and chemotherapy | |
dc.journal.titleabbreviation | Antimicrob Agents Chemother | |
dc.language.iso | en | |
dc.organization | Instituto de Biomedicina de Sevilla-IBIS | |
dc.organization | Hospital Universitario Virgen del Rocío | |
dc.provenance | Realizada la curación de contenido 05/06/2025. | |
dc.publisher | American Society for Microbiology | |
dc.pubmedtype | Journal Article | |
dc.pubmedtype | Research Support, Non-U.S. Gov't | |
dc.relation.publisherversion | https://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.accessRights | Restricted Access | |
dc.subject | Acinetobacter | |
dc.subject | antibiotic resistance | |
dc.subject | genome analysis | |
dc.subject | lipid A | |
dc.subject | virulence | |
dc.subject.decs | Colistina | |
dc.subject.decs | Reacción en cadena de la polimerasa | |
dc.subject.decs | Infecciones | |
dc.subject.decs | Virulencia | |
dc.subject.decs | Acinetobacter baumannii | |
dc.subject.decs | Mutación puntual | |
dc.subject.decs | Aminoácidos | |
dc.subject.mesh | Acinetobacter Infections | |
dc.subject.mesh | Acinetobacter baumannii | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Anti-Bacterial Agents | |
dc.subject.mesh | Bacterial Proteins | |
dc.subject.mesh | Colistin | |
dc.subject.mesh | Disease Models, Animal | |
dc.subject.mesh | Drug Resistance, Bacterial | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Lipid A | |
dc.subject.mesh | Microbial Sensitivity Tests | |
dc.subject.mesh | Moths | |
dc.subject.mesh | Transcription Factors | |
dc.title | Investigation of Novel pmrB and eptA Mutations in Isogenic Acinetobacter baumannii Isolates Associated with Colistin Resistance and Increased Virulence In Vivo. | |
dc.type | research article | |
dc.type.hasVersion | VoR | |
dc.volume.number | 63 | |
dspace.entity.type | Publication |
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