Genomic Variations in Drug Resistant <i>Mycobacterium tuberculosis</i> Strains Collected from Patients with Different Localization of Infection

• Main Authors: Ekaterina Chernyaeva, Mikhail Rotkevich, Ksenia Krasheninnikova, Alla Lapidus, Dmitrii E. Polev, Natalia Solovieva, Viacheslav Zhuravlev, Piotr Yablonsky, Stephen J. O’Brien
• Format: Article
• Language: English
• Published: MDPI AG 2021-12-01
• Series: Antibiotics
• Subjects: <i>Mycobacterium tuberculosis</i>; drug resistance; pulmonary tuberculosis; extrapulmonary tuberculosis; whole-genome sequencing
• Online Access: https://www.mdpi.com/2079-6382/10/1/27

<i>Mycobacterium tuberculosis</i> is a highly studied pathogen due to public health importance. Despite this, problems like early drug resistance, diagnostics and treatment success prediction are still not fully resolved. Here, we analyze the incidence of point mutations widely used for drug resistance detection in laboratory practice and conduct comparative analysis of whole-genome sequence (WGS) for clinical <i>M. tuberculosis</i> strains collected from patients with pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis (XPTB) localization. A total of 72 pulmonary and 73 extrapulmonary microbiologically characterized <i>M. tuberculosis</i> isolates were collected from patients from 2007 to 2014 in Russia. Genomic DNA was used for WGS and obtained data allowed identifying major mutations known to be associated with drug resistance to first-line and second-line antituberculous drugs. In some cases previously described mutations were not identified. Using genome-based phylogenetic analysis we identified <i>M. tuberculosis</i> substrains associated with distinctions in the occurrence in PTB vs. XPTB cases. Phylogenetic analyses did reveal <i>M. tuberculosis</i> genetic substrains associated with TB localization. XPTB was associated with Beijing sublineages Central Asia (Beijing CAO), Central Asia Clade A (Beijing A) and 4.8 groups, while PTB localization was associated with group LAM (4.3). Further, the XPTB strain in some cases showed elevated drug resistance patterns relative to PTB isolates. HIV was significantly associated with the development of XPTB in the Beijing B0/W148 group and among unclustered Beijing isolates.