A multifaceted interplay between virulence, drug resistance, and the phylogeographic landscape of Mycobacterium tuberculosis
ABSTRACT Latin-American Mediterranean (LAM) family is one of the most significant and global genotypes of Mycobacterium tuberculosis. Here, we used the murine model to study the virulence and lethality of the genetically and epidemiologically distinct LAM strains. The pathobiological characteristics...
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ftdoajarticles:oai:doaj.org/article:6c7be84186ec49b898c73f07246da4ae 2023-11-12T04:23:05+01:00 A multifaceted interplay between virulence, drug resistance, and the phylogeographic landscape of Mycobacterium tuberculosis Igor Mokrousov Tatiana Vinogradova Marine Dogonadze Natalia Zabolotnykh Anna Vyazovaya Maria Vitovskaya Natalia Solovieva Boris Ariel 2023-10-01T00:00:00Z https://doi.org/10.1128/spectrum.01392-23 https://doaj.org/article/6c7be84186ec49b898c73f07246da4ae EN eng American Society for Microbiology https://journals.asm.org/doi/10.1128/spectrum.01392-23 https://doaj.org/toc/2165-0497 doi:10.1128/spectrum.01392-23 2165-0497 https://doaj.org/article/6c7be84186ec49b898c73f07246da4ae Microbiology Spectrum, Vol 11, Iss 5 (2023) Mycobacterium tuberculosis virulence multidrug resistance murine model phylogeography Microbiology QR1-502 article 2023 ftdoajarticles https://doi.org/10.1128/spectrum.01392-23 2023-10-22T00:41:43Z ABSTRACT Latin-American Mediterranean (LAM) family is one of the most significant and global genotypes of Mycobacterium tuberculosis. Here, we used the murine model to study the virulence and lethality of the genetically and epidemiologically distinct LAM strains. The pathobiological characteristics of the four LAM strains (three drug resistant and one drug susceptible) and the susceptible reference strain H37Rv were studied in the C57BL/6 mouse model. The whole-genome sequencing was performed using the HiSeq Illumina platform, followed by bioinformatics and phylogenetic analysis. The susceptible strain H37Rv showed the highest virulence. Drug-susceptible LAM strain (spoligotype SIT264) was more virulent than three multidrug-resistant (MDR) strains (SIT252, SIT254, and SIT266). All three MDR isolates were low lethal, while the susceptible isolate and H37Rv were moderately/highly lethal. Putting the genomic, phenotypic, and virulence features of the LAM strains/spoligotypes in the context of their dynamic phylogeography over 20 years reveals three types of relationships between virulence, resistance, and transmission. First, the most virulent and more lethal drug-susceptible SIT264 increased its circulation in parts of Russia. Second, moderately virulent and pre-XDR SIT266 was prevalent in Belarus and continues to be visible in North-West Russia. Third, the low virulent and MDR strain SIT252 previously considered as emerging has disappeared from the population. These findings suggest that strain virulence impacts the transmission, irrespective of drug resistance properties. The increasing circulation of susceptible but more virulent and lethal strains implies that personalized TB treatment should consider not only resistance but also the virulence of the infecting M. tuberculosis strains. IMPORTANCE The study is multidisciplinary and investigates the epidemically/clinically important and global lineage of Mycobacterium tuberculosis, named Latin-American-Mediterranean (LAM), yet insufficiently studied with regard ... Article in Journal/Newspaper North-West Russia Directory of Open Access Journals: DOAJ Articles Microbiology Spectrum 11 5 |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Mycobacterium tuberculosis virulence multidrug resistance murine model phylogeography Microbiology QR1-502 |
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Mycobacterium tuberculosis virulence multidrug resistance murine model phylogeography Microbiology QR1-502 Igor Mokrousov Tatiana Vinogradova Marine Dogonadze Natalia Zabolotnykh Anna Vyazovaya Maria Vitovskaya Natalia Solovieva Boris Ariel A multifaceted interplay between virulence, drug resistance, and the phylogeographic landscape of Mycobacterium tuberculosis |
topic_facet |
Mycobacterium tuberculosis virulence multidrug resistance murine model phylogeography Microbiology QR1-502 |
description |
ABSTRACT Latin-American Mediterranean (LAM) family is one of the most significant and global genotypes of Mycobacterium tuberculosis. Here, we used the murine model to study the virulence and lethality of the genetically and epidemiologically distinct LAM strains. The pathobiological characteristics of the four LAM strains (three drug resistant and one drug susceptible) and the susceptible reference strain H37Rv were studied in the C57BL/6 mouse model. The whole-genome sequencing was performed using the HiSeq Illumina platform, followed by bioinformatics and phylogenetic analysis. The susceptible strain H37Rv showed the highest virulence. Drug-susceptible LAM strain (spoligotype SIT264) was more virulent than three multidrug-resistant (MDR) strains (SIT252, SIT254, and SIT266). All three MDR isolates were low lethal, while the susceptible isolate and H37Rv were moderately/highly lethal. Putting the genomic, phenotypic, and virulence features of the LAM strains/spoligotypes in the context of their dynamic phylogeography over 20 years reveals three types of relationships between virulence, resistance, and transmission. First, the most virulent and more lethal drug-susceptible SIT264 increased its circulation in parts of Russia. Second, moderately virulent and pre-XDR SIT266 was prevalent in Belarus and continues to be visible in North-West Russia. Third, the low virulent and MDR strain SIT252 previously considered as emerging has disappeared from the population. These findings suggest that strain virulence impacts the transmission, irrespective of drug resistance properties. The increasing circulation of susceptible but more virulent and lethal strains implies that personalized TB treatment should consider not only resistance but also the virulence of the infecting M. tuberculosis strains. IMPORTANCE The study is multidisciplinary and investigates the epidemically/clinically important and global lineage of Mycobacterium tuberculosis, named Latin-American-Mediterranean (LAM), yet insufficiently studied with regard ... |
format |
Article in Journal/Newspaper |
author |
Igor Mokrousov Tatiana Vinogradova Marine Dogonadze Natalia Zabolotnykh Anna Vyazovaya Maria Vitovskaya Natalia Solovieva Boris Ariel |
author_facet |
Igor Mokrousov Tatiana Vinogradova Marine Dogonadze Natalia Zabolotnykh Anna Vyazovaya Maria Vitovskaya Natalia Solovieva Boris Ariel |
author_sort |
Igor Mokrousov |
title |
A multifaceted interplay between virulence, drug resistance, and the phylogeographic landscape of Mycobacterium tuberculosis |
title_short |
A multifaceted interplay between virulence, drug resistance, and the phylogeographic landscape of Mycobacterium tuberculosis |
title_full |
A multifaceted interplay between virulence, drug resistance, and the phylogeographic landscape of Mycobacterium tuberculosis |
title_fullStr |
A multifaceted interplay between virulence, drug resistance, and the phylogeographic landscape of Mycobacterium tuberculosis |
title_full_unstemmed |
A multifaceted interplay between virulence, drug resistance, and the phylogeographic landscape of Mycobacterium tuberculosis |
title_sort |
multifaceted interplay between virulence, drug resistance, and the phylogeographic landscape of mycobacterium tuberculosis |
publisher |
American Society for Microbiology |
publishDate |
2023 |
url |
https://doi.org/10.1128/spectrum.01392-23 https://doaj.org/article/6c7be84186ec49b898c73f07246da4ae |
genre |
North-West Russia |
genre_facet |
North-West Russia |
op_source |
Microbiology Spectrum, Vol 11, Iss 5 (2023) |
op_relation |
https://journals.asm.org/doi/10.1128/spectrum.01392-23 https://doaj.org/toc/2165-0497 doi:10.1128/spectrum.01392-23 2165-0497 https://doaj.org/article/6c7be84186ec49b898c73f07246da4ae |
op_doi |
https://doi.org/10.1128/spectrum.01392-23 |
container_title |
Microbiology Spectrum |
container_volume |
11 |
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5 |
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1782337961725001728 |