Drug Resistance Patterns of Mycobacterium Tuberculosis Isolated From Pulmonary Tuberculosis Cases among HIV Seropositive and Seronegative Individuals

Mycobacterium tuberculosis 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 M. tuberculosis strains collected from patients with pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis (XPTB) localization. A total of 72 pulmonary and 73 extrapulmonary microbiologically characterized M. tuberculosis 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 M. tuberculosis substrains associated with distinctions in the occurrence in PTB vs. XPTB cases. Phylogenetic analyses did reveal M. tuberculosis 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.

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Molecular characteristics of drug-resistance Mycobacterium tuberculosis strains isolated from extra pulmonary tuberculosis sites

Enfermedades infecciosas y microbiologia clinica (English ed ) ◽

10.1016/j.eimce.2020.04.007 ◽

2021 ◽

Vol 39 (4) ◽

pp. 168-173

Author(s):

Tongxin Li ◽

Tao Shi ◽

Ying Sun ◽

Fei Chen ◽

Wenxue Jiang ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Pulmonary Tuberculosis ◽

Molecular Characteristics ◽

Extra Pulmonary Tuberculosis ◽

Extra Pulmonary

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Frequency and patterns of first- and second-line drug resistance-conferring mutations in Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in a cross-sectional study in Tigray Region, Ethiopia

Journal of Global Antimicrobial Resistance ◽

10.1016/j.jgar.2020.11.017 ◽

2021 ◽

Vol 24 ◽

pp. 6-13

Author(s):

Letemichael Negash Welekidan ◽

Eystein Skjerve ◽

Tsehaye Asmelash Dejene ◽

Mengistu Welday Gebremichael ◽

Ola Brynildsrud ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Pulmonary Tuberculosis ◽

Cross Sectional Study ◽

Second Line ◽

Sectional Study ◽

Cross Sectional ◽

Tuberculosis Patients ◽

Tigray Region ◽

Line Drug

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Mycobacterium tuberculosis genotypic drug resistance patterns and clustering in Jayapura, Papua, Indonesia

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.14.0350 ◽

2015 ◽

Vol 19 (4) ◽

pp. 428-433 ◽

Cited By ~ 6

Author(s):

L. Chaidir ◽

S. Sengstake ◽

J. de Beer ◽

H. Krismawati ◽

F. D. Lestari ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Resistance Patterns

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Drug resistance profile of Mycobacterium tuberculosis isolates from pulmonary tuberculosis patients in Jos, Nigeria

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1016/j.trstmh.2008.08.004 ◽

2009 ◽

Vol 103 (1) ◽

pp. 67-71 ◽

Cited By ~ 10

Author(s):

A.E. Ani ◽

J. Idoko ◽

Y.B. Dalyop ◽

S.L. Pitmang

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Pulmonary Tuberculosis ◽

Tuberculosis Patients ◽

Resistance Profile ◽

Drug Resistance Profile

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Role of embB Codon 306 Mutations in Mycobacterium tuberculosis Revisited: a Novel Association with Broad Drug Resistance and IS6110 Clustering Rather than Ethambutol Resistance

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.9.3794-3802.2005 ◽

2005 ◽

Vol 49 (9) ◽

pp. 3794-3802 ◽

Cited By ~ 79

Author(s):

Manzour Hernando Hazbón ◽

Miriam Bobadilla del Valle ◽

Marta Inírida Guerrero ◽

Mandira Varma-Basil ◽

Ingrid Filliol ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Odds Ratio ◽

Univariate Analysis ◽

Drug Susceptibility ◽

Drug Resistant ◽

Development Of Resistance ◽

Resistance Patterns ◽

Novel Association

ABSTRACT Mutations at position 306 of embB (embB306) have been proposed as a marker for ethambutol resistance in Mycobacterium tuberculosis; however, recent reports of embB306 mutations in ethambutol-susceptible isolates caused us to question the biological role of this mutation. We tested 1,020 clinical M. tuberculosis isolates with different drug susceptibility patterns and of different geographical origins for associations between embB306 mutations, drug resistance patterns, and major genetic group. One hundred isolates (10%) contained a mutation in embB306; however, only 55 of these mutants were ethambutol resistant. Mutations in embB306 could not be uniquely associated with any particular type of drug resistance and were found in all three major genetic groups. A striking association was observed between these mutations and resistance to any drug (P < 0.001), and the association between embB306 mutations and resistance to increasing numbers of drugs was highly significant (P < 0.001 for trend). We examined the association between embB306 mutations and IS6110 clustering (as a proxy for transmission) among all drug-resistant isolates. Mutations in embB306 were significantly associated with clustering by univariate analysis (odds ratio, 2.44; P = 0.004). In a multivariate model that also included mutations in katG315, katG463, gyrA95, and kasA269, only mutations in embB306 (odds ratio, 2.14; P = 0.008) and katG315 (odds ratio, 1.99; P = 0.015) were found to be independently associated with clustering. In conclusion, embB306 mutations do not cause classical ethambutol resistance but may predispose M. tuberculosis isolates to the development of resistance to increasing numbers of antibiotics and may increase the ability of drug-resistant isolates to be transmitted between subjects.

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