Whole genome sequencing analysis of Mycobacterium tuberculosis reveals circulating strain types and drug-resistance mutations in the Philippines.

Mycobacterium tuberculosis / genetics Philippines / epidemiology Humans Whole Genome Sequencing / methods Mutation Tuberculosis, Multidrug-Resistant / microbiology Antitubercular Agents / pharmacology Extensively Drug-Resistant Tuberculosis / microbiology Genome, Bacterial Drug Resistance, Multiple, Bacterial / genetics Genotype Phylogeny Microbial Sensitivity Tests

Journal

Scientific reports

ISSN: 2045-2322

Titre abrégé: Sci Rep

Pays: England

ID NLM: 101563288

Informations de publication

Date de publication:
23 Aug 2024

Historique:

received: 27 02 2024

accepted: 16 08 2024

medline: 24 8 2024

pubmed: 24 8 2024

entrez: 23 8 2024

Statut: epublish

Résumé

The Philippines is a high-incidence country for tuberculosis, with the increasing prevalence of multi- (MDR-TB) and extensively-drug (XDR-TB) resistant Mycobacterium tuberculosis strains posing difficulties to disease control. Understanding the genetic diversity of circulating strains can provide insights into underlying drug resistance mutations and transmission dynamics, thereby assisting the design of diagnostic tools, including those using next generation sequencing (NGS) platforms. By analysing genome sequencing data of 732 isolates from Philippines drug-resistance survey collections spanning from 2011 to 2019, we found that the majority belonged to lineages L1 (531/732; 72.5%) and L4 (European-American; n = 174; 23.8%), with the Manila strain (L1.2.1.2.1) being the most prominent (475/531). Approximately two-thirds of isolates were found to be at least MDR-TB (483/732; 66.0%), and potential XDR-TB genotypic resistance was observed (3/732; 0.4%), highlighting an emerging problem in the country. Genotypic resistance was highly concordant with laboratory drug susceptibility testing. By finding isolates with (near-)identical genomic variation, five major clusters containing a total of 114 isolates were identified: all containing either L1 or L4 isolates with at least MDR-TB resistance and spanning multiple years of collection. Closer inspection of clusters revealed transmission in prisons, some involving isolates with XDR-TB, and mutations linked to third-line drug bedaquiline. We have also identified previously unreported mutations linked to resistance for isoniazid, rifampicin, ethambutol, and fluoroquinolones. Overall, this study provides important insights into the genetic diversity, transmission and circulating drug resistance mutations of M. tuberculosis in the Philippines, thereby informing clinical and surveillance decision-making, which is increasingly using NGS platforms.

Identifiants

DOI: 10.1038/s41598-024-70471-x PMID: 39179783

pubmed: 39179783

doi: 10.1038/s41598-024-70471-x

pii: 10.1038/s41598-024-70471-x

doi:

Substances chimiques

Antitubercular Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

19602

Subventions

Organisme : Biotechnology and Biological Sciences Research Council

ID : BB/T008709/1

Pays : United Kingdom

Organisme : Medical Research Council,United Kingdom

ID : MR/N010469/1

Organisme : Medical Research Council,United Kingdom

ID : MR/N010469/1

Organisme : Engineering and Physical Sciences Research Council

ID : EP/Y018842/1

Organisme : Engineering and Physical Sciences Research Council

ID : EP/Y018842/1

Organisme : British Council

ID : 261868591

Informations de copyright

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