Your browser doesn't support javascript.
loading
Evolutionary paths to macrolide resistance in a Neisseria commensal converge on ribosomal genes through short sequence duplications.
Raisman, Jordan C; Fiore, Michael A; Tomin, Lucille; Adjei, Joseph K O; Aswad, Virginia X; Chu, Jonathan; Domondon, Christina J; Donahue, Ben A; Masciotti, Claudia A; McGrath, Connor G; Melita, Jo; Podbielski, Paul A; Schreiner, Madelyn R; Trumpore, Lauren J; Wengert, Peter C; Wrightstone, Emalee A; Hudson, André O; Wadsworth, Crista B.
Afiliação
  • Raisman JC; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Fiore MA; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Tomin L; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Adjei JKO; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Aswad VX; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Chu J; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Domondon CJ; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Donahue BA; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Masciotti CA; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • McGrath CG; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Melita J; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Podbielski PA; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Schreiner MR; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Trumpore LJ; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Wengert PC; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Wrightstone EA; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Hudson AO; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
  • Wadsworth CB; Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, United States of America.
PLoS One ; 17(1): e0262370, 2022.
Article em En | MEDLINE | ID: mdl-35025928
Neisseria commensals are an indisputable source of resistance for their pathogenic relatives. However, the evolutionary paths commensal species take to reduced susceptibility in this genus have been relatively underexplored. Here, we leverage in vitro selection as a powerful screen to identify the genetic adaptations that produce azithromycin resistance (≥ 2 µg/mL) in the Neisseria commensal, N. elongata. Across multiple lineages (n = 7/16), we find mutations that reduce susceptibility to azithromycin converge on the locus encoding the 50S ribosomal L34 protein (rpmH) and the intergenic region proximal to the 30S ribosomal S3 protein (rpsC) through short tandem duplication events. Interestingly, one of the laboratory evolved mutations in rpmH is identical (7LKRTYQ12), and two nearly identical, to those recently reported to contribute to high-level azithromycin resistance in N. gonorrhoeae. Transformations into the ancestral N. elongata lineage confirmed the causality of both rpmH and rpsC mutations. Though most lineages inheriting duplications suffered in vitro fitness costs, one variant showed no growth defect, suggesting the possibility that it may be sustained in natural populations. Ultimately, studies like this will be critical for predicting commensal alleles that could rapidly disseminate into pathogen populations via allelic exchange across recombinogenic microbial genera.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Macrolídeos / Farmacorresistência Bacteriana / Neisseria Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Macrolídeos / Farmacorresistência Bacteriana / Neisseria Idioma: En Ano de publicação: 2022 Tipo de documento: Article