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Pre-existing chromosomal polymorphisms in pathogenic E. coli potentiate the evolution of resistance to a last-resort antibiotic

Bacterial pathogens show high levels of chromosomal genetic diversity, but the influence of this diversity on the evolution of antibiotic resistance by plasmid acquisition remains unclear. Here, we address this problem in the context of colistin, a ‘last line of defence’ antibiotic. Using experiment...

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Autores principales: Jangir, Pramod K, Yang, Qiue, Shaw, Liam P, Caballero, Julio Diaz, Ogunlana, Lois, Wheatley, Rachel, Walsh, Timothy, MacLean, R Craig
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363117/
https://www.ncbi.nlm.nih.gov/pubmed/35943060
http://dx.doi.org/10.7554/eLife.78834
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author Jangir, Pramod K
Yang, Qiue
Shaw, Liam P
Caballero, Julio Diaz
Ogunlana, Lois
Wheatley, Rachel
Walsh, Timothy
MacLean, R Craig
author_facet Jangir, Pramod K
Yang, Qiue
Shaw, Liam P
Caballero, Julio Diaz
Ogunlana, Lois
Wheatley, Rachel
Walsh, Timothy
MacLean, R Craig
author_sort Jangir, Pramod K
collection PubMed
description Bacterial pathogens show high levels of chromosomal genetic diversity, but the influence of this diversity on the evolution of antibiotic resistance by plasmid acquisition remains unclear. Here, we address this problem in the context of colistin, a ‘last line of defence’ antibiotic. Using experimental evolution, we show that a plasmid carrying the MCR-1 colistin resistance gene dramatically increases the ability of Escherichia coli to evolve high-level colistin resistance by acquiring mutations in lpxC, an essential chromosomal gene involved in lipopolysaccharide biosynthesis. Crucially, lpxC mutations increase colistin resistance in the presence of the MCR-1 gene, but decrease the resistance of wild-type cells, revealing positive sign epistasis for antibiotic resistance between the chromosomal mutations and a mobile resistance gene. Analysis of public genomic datasets shows that lpxC polymorphisms are common in pathogenic E. coli, including those carrying MCR-1, highlighting the clinical relevance of this interaction. Importantly, lpxC diversity is high in pathogenic E. coli from regions with no history of MCR-1 acquisition, suggesting that pre-existing lpxC polymorphisms potentiated the evolution of high-level colistin resistance by MCR-1 acquisition. More broadly, these findings highlight the importance of standing genetic variation and plasmid/chromosomal interactions in the evolutionary dynamics of antibiotic resistance.
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spelling pubmed-93631172022-08-10 Pre-existing chromosomal polymorphisms in pathogenic E. coli potentiate the evolution of resistance to a last-resort antibiotic Jangir, Pramod K Yang, Qiue Shaw, Liam P Caballero, Julio Diaz Ogunlana, Lois Wheatley, Rachel Walsh, Timothy MacLean, R Craig eLife Evolutionary Biology Bacterial pathogens show high levels of chromosomal genetic diversity, but the influence of this diversity on the evolution of antibiotic resistance by plasmid acquisition remains unclear. Here, we address this problem in the context of colistin, a ‘last line of defence’ antibiotic. Using experimental evolution, we show that a plasmid carrying the MCR-1 colistin resistance gene dramatically increases the ability of Escherichia coli to evolve high-level colistin resistance by acquiring mutations in lpxC, an essential chromosomal gene involved in lipopolysaccharide biosynthesis. Crucially, lpxC mutations increase colistin resistance in the presence of the MCR-1 gene, but decrease the resistance of wild-type cells, revealing positive sign epistasis for antibiotic resistance between the chromosomal mutations and a mobile resistance gene. Analysis of public genomic datasets shows that lpxC polymorphisms are common in pathogenic E. coli, including those carrying MCR-1, highlighting the clinical relevance of this interaction. Importantly, lpxC diversity is high in pathogenic E. coli from regions with no history of MCR-1 acquisition, suggesting that pre-existing lpxC polymorphisms potentiated the evolution of high-level colistin resistance by MCR-1 acquisition. More broadly, these findings highlight the importance of standing genetic variation and plasmid/chromosomal interactions in the evolutionary dynamics of antibiotic resistance. eLife Sciences Publications, Ltd 2022-08-09 /pmc/articles/PMC9363117/ /pubmed/35943060 http://dx.doi.org/10.7554/eLife.78834 Text en © 2022, Jangir, Yang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Evolutionary Biology
Jangir, Pramod K
Yang, Qiue
Shaw, Liam P
Caballero, Julio Diaz
Ogunlana, Lois
Wheatley, Rachel
Walsh, Timothy
MacLean, R Craig
Pre-existing chromosomal polymorphisms in pathogenic E. coli potentiate the evolution of resistance to a last-resort antibiotic
title Pre-existing chromosomal polymorphisms in pathogenic E. coli potentiate the evolution of resistance to a last-resort antibiotic
title_full Pre-existing chromosomal polymorphisms in pathogenic E. coli potentiate the evolution of resistance to a last-resort antibiotic
title_fullStr Pre-existing chromosomal polymorphisms in pathogenic E. coli potentiate the evolution of resistance to a last-resort antibiotic
title_full_unstemmed Pre-existing chromosomal polymorphisms in pathogenic E. coli potentiate the evolution of resistance to a last-resort antibiotic
title_short Pre-existing chromosomal polymorphisms in pathogenic E. coli potentiate the evolution of resistance to a last-resort antibiotic
title_sort pre-existing chromosomal polymorphisms in pathogenic e. coli potentiate the evolution of resistance to a last-resort antibiotic
topic Evolutionary Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363117/
https://www.ncbi.nlm.nih.gov/pubmed/35943060
http://dx.doi.org/10.7554/eLife.78834
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