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Evolutionary paths to macrolide resistance in a Neisseria commensal converge on ribosomal genes through short sequence duplications

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 g...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758062/
https://www.ncbi.nlm.nih.gov/pubmed/35025928
http://dx.doi.org/10.1371/journal.pone.0262370
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author 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.
author_facet 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.
author_sort Raisman, Jordan C.
collection PubMed
description 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.
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spelling pubmed-87580622022-01-14 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. PLoS One Research Article 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. Public Library of Science 2022-01-13 /pmc/articles/PMC8758062/ /pubmed/35025928 http://dx.doi.org/10.1371/journal.pone.0262370 Text en © 2022 Raisman et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
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.
Evolutionary paths to macrolide resistance in a Neisseria commensal converge on ribosomal genes through short sequence duplications
title Evolutionary paths to macrolide resistance in a Neisseria commensal converge on ribosomal genes through short sequence duplications
title_full Evolutionary paths to macrolide resistance in a Neisseria commensal converge on ribosomal genes through short sequence duplications
title_fullStr Evolutionary paths to macrolide resistance in a Neisseria commensal converge on ribosomal genes through short sequence duplications
title_full_unstemmed Evolutionary paths to macrolide resistance in a Neisseria commensal converge on ribosomal genes through short sequence duplications
title_short Evolutionary paths to macrolide resistance in a Neisseria commensal converge on ribosomal genes through short sequence duplications
title_sort evolutionary paths to macrolide resistance in a neisseria commensal converge on ribosomal genes through short sequence duplications
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758062/
https://www.ncbi.nlm.nih.gov/pubmed/35025928
http://dx.doi.org/10.1371/journal.pone.0262370
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