Heteroresistance to the model antimicrobial peptide polymyxin B in the emerging Neisseria meningitidis lineage 11.2 urethritis clade: mutations in the pilMNOPQ operon

dc.contributor.authorTzeng, Yih-Ling
dc.contributor.authorBerman, Zachary
dc.contributor.authorToh, Evelyn
dc.contributor.authorBazan, Jose A.
dc.contributor.authorTurner, Abigail Norris
dc.contributor.authorRetchless, Adam C.
dc.contributor.authorWang, Xin
dc.contributor.authorNelson, David E.
dc.contributor.authorStephens, David S.
dc.contributor.departmentMicrobiology and Immunology, School of Medicineen_US
dc.date.accessioned2020-03-17T15:29:11Z
dc.date.available2020-03-17T15:29:11Z
dc.date.issued2019-01
dc.description.abstractClusters of Neisseria meningitidis (Nm) urethritis among primarily heterosexual males in multiple US cities have been attributed to a unique non‐encapsulated meningococcal clade (the US Nm urethritis clade, US_NmUC) within the hypervirulent clonal complex 11. Resistance to antimicrobial peptides (AMPs) is a key feature of urogenital pathogenesis of the closely related species, Neisseria gonorrhoeae. The US_NmUC isolates were found to be highly resistant to the model AMP, polymyxin B (PmB, MICs 64–256 µg ml–1). The isolates also demonstrated stable subpopulations of heteroresistant colonies that showed near total resistant to PmB (MICs 384–1024 µg ml–1) and colistin (MIC 256 µg ml–1) as well as enhanced LL‐37 resistance. This is the first observation of heteroresistance in N. meningitidis. Consistent with previous findings, overall PmB resistance in US_NmUC isolates was due to active Mtr efflux and LptA‐mediated lipid A modification. However, whole genome sequencing, variant analyses and directed mutagenesis revealed that the heteroresistance phenotypes and very high‐level AMP resistance were the result of point mutations and IS1655 element movement in the pilMNOPQ operon, encoding the type IV pilin biogenesis apparatus. Cross‐resistance to other classes of antibiotics was also observed in the heteroresistant colonies. High‐level resistance to AMPs may contribute to the pathogenesis of US_NmUC.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationTzeng, Y. L., Berman, Z., Toh, E., Bazan, J. A., Turner, A. N., Retchless, A. C., ... & Stephens, D. S. (2019). Heteroresistance to the model antimicrobial peptide polymyxin B in the emerging Neisseria meningitidis lineage 11.2 urethritis clade: mutations in the pilMNOPQ operon. Molecular microbiology, 111(1), 254-268. 10.1111/mmi.14153en_US
dc.identifier.issn1365-2958en_US
dc.identifier.urihttps://hdl.handle.net/1805/22339
dc.language.isoen_USen_US
dc.publisherWileyen_US
dc.relation.isversionof10.1111/mmi.14153en_US
dc.relation.journalMolecular Microbiologyen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectNeisseria meningitidisen_US
dc.subjectMeningococcal urethritisen_US
dc.subjectHeteroresistanceen_US
dc.subjectPolymyxin Ben_US
dc.subjectAntimicrobial peptideen_US
dc.subjectpilQen_US
dc.titleHeteroresistance to the model antimicrobial peptide polymyxin B in the emerging Neisseria meningitidis lineage 11.2 urethritis clade: mutations in the pilMNOPQ operonen_US
dc.typeArticleen_US
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