In Vivo-Selected Compensatory Mutations Restore the Fitness Cost of Mosaic penA Alleles That Confer Ceftriaxone Resistance in Neisseria gonorrhoeae.

ABSTRACT: Resistance to ceftriaxone in Neisseria gonorrhoeae is mainly conferred by mosaic penA alleles that encode penicillin-binding protein 2 (PBP2) variants with markedly lower rates of acylation by ceftriaxone. To assess the impact of these mosaic penA alleles on gonococcal fitness, we introduced the mosaic penA alleles from two ceftriaxone-resistant (Cro^r) clinical isolates (H041 and F89) into a Cro^s strain (FA19) by allelic exchange and showed that the resultant Cro^r mutants were significantly outcompeted by the Cro^s parent strain in vitro and in a murine infection model. Four Cro^r compensatory mutants of FA19 penA41 were isolated independently from mice that outcompeted the parent strain both

SUBMITTER: Vincent LR 

PROVIDER: S-EPMC5885032 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature