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Heteroresistance to the model antimicrobial peptide polymyxin B in the emerging Neisseria meningitidis lineage 11.2 urethritis clade: mutations in the pilMNOPQ operon
Author(s) -
Tzeng YihLing,
Berman Zachary,
Toh Evelyn,
Bazan Jose A.,
Turner Abigail Norris,
Retchless Adam C.,
Wang Xin,
Nelson David E.,
Stephens David S.
Publication year - 2019
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14153
Subject(s) - biology , neisseria meningitidis , microbiology and biotechnology , neisseria , neisseria gonorrhoeae , polymyxin b , urethritis , operon , lineage (genetic) , virology , pilin , genetics , antibiotic resistance , clade , antimicrobial peptides , antimicrobial , gene , virulence , antibiotics , bacteria , escherichia coli , phylogenetics , pilus , medicine , urology
Summary Clusters 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.