Insertion and deletion evolution reflects antibiotics selection pressure in a Mycobacterium tuberculosis outbreak.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
22
01
2020
accepted:
18
08
2020
revised:
12
10
2020
pubmed:
1
10
2020
medline:
13
11
2020
entrez:
30
9
2020
Statut:
epublish
Résumé
In genome evolution, genetic variants are the source of diversity, which natural selection acts upon. Treatment of human tuberculosis (TB) induces a strong selection pressure for the emergence of antibiotic resistance-conferring variants in the infecting Mycobacterium tuberculosis (MTB) strains. MTB evolution in response to treatment has been intensively studied and mainly attributed to point substitutions. However, the frequency and contribution of insertions and deletions (indels) to MTB genome evolution remains poorly understood. Here, we analyzed a multi-drug resistant MTB outbreak for the presence of high-quality indels and substitutions. We find that indels are significantly enriched in genes conferring antibiotic resistance. Furthermore, we show that indels are inherited during the outbreak and follow a molecular clock with an evolutionary rate of 5.37e-9 indels/site/year, which is 23 times lower than the substitution rate. Inherited indels may co-occur with substitutions in genes along related biological pathways; examples are iron storage and resistance to second-line antibiotics. This suggests that epistatic interactions between indels and substitutions affect antibiotic resistance and compensatory evolution in MTB.
Identifiants
pubmed: 32997707
doi: 10.1371/journal.ppat.1008357
pii: PPATHOGENS-D-20-00142
pmc: PMC7549793
doi:
Substances chimiques
Anti-Bacterial Agents
0
Antitubercular Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008357Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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