Analysis of drug resistance mutations in pulmonary Mycobacterium tuberculosis isolates in the Southern coastal region of Andhra Pradesh, India

ABSTRACTBacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (TB). Only a few studies have reported on the interactions between different bacterial factors. We studied drug-resistantMycobacterium tuberculosisisolates from a nationwide study conducted from 2000 to 2008 in Switzerland. We determined quantitative drug resistance levels of first-line drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant genes. We determined recent transmission by molecular methods and collected clinical data. Overall, we analyzed 158 isolates that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which were multidrug resistant. Among 154 isoniazid-resistant strains,katGmutations were associated with high-level andinhApromoter mutations with low-level drug resistance. OnlykatG(S315T) (65.6% of all isoniazid-resistant strains) andinhApromoter −15C/T (22.7%) were found in molecular clusters.M. tuberculosislineage 2 (includes Beijing genotype) was associated with any drug resistance (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6;P< 0.0001). Lineage 1 was associated withinhApromoter −15C/T mutations (OR, 6.4; 95% CI, 2.0 to 20.7;P= 0.002). We found that the genetic strain background influences the level of isoniazid resistance conveyed by particular mutations (interaction tests of drug resistance mutations across all lineages;P< 0.0001). In conclusion,M. tuberculosisdrug resistance mutations were associated with various levels of drug resistance and transmission, andM. tuberculosislineages were associated with particular drug resistance-conferring mutations and phenotypic drug resistance. Our study also supports a role for epistatic interactions between different drug resistance mutations and strain genetic backgrounds inM. tuberculosisdrug resistance.

Download Full-text

Positive epistasis of major low-cost drug resistance mutations rpoB 531-TTG and katG 315-ACC depends on the phylogenetic background of Mycobacterium tuberculosis strains

International Journal of Antimicrobial Agents ◽

10.1016/j.ijantimicag.2017.02.009 ◽

2017 ◽

Vol 49 (6) ◽

pp. 757-762 ◽

Cited By ~ 8

Author(s):

Qin-jing Li ◽

Wei-wei Jiao ◽

Qing-qin Yin ◽

Ying-jia Li ◽

Jie-qiong Li ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Low Cost ◽

Resistance Mutations ◽

Drug Resistance Mutations

Download Full-text

A computational perspective on the dynamic behaviour of recurrent drug resistance mutations in the pncA gene from Mycobacterium tuberculosis

RSC Advances ◽

10.1039/d0ra09326b ◽

2021 ◽

Vol 11 (4) ◽

pp. 2476-2486

Author(s):

Taimoor Khan ◽

Abbas Khan ◽

Syed Shujait Ali ◽

Shahid Ali ◽

Dong-Qing Wei

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Causes Of Death ◽

Dynamic Behaviour ◽

Multidrug Resistant ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Computational Perspective

Tuberculosis is still one of the top 10 causes of death worldwide, particularly with the emergence of multidrug-resistant tuberculosis.

Download Full-text

Mycobacterium tuberculosis whole genome sequencing provides insights into the Manila strain and drug-resistance mutations in the Philippines

Scientific Reports ◽

10.1038/s41598-019-45566-5 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Jody E. Phelan ◽

Dodge R. Lim ◽

Satoshi Mitarai ◽

Paola Florez de Sessions ◽

Ma. Angelica A. Tujan ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

The Philippines ◽

Whole Genome ◽

Resistance Mutations ◽

Drug Resistance Mutations

Download Full-text

MYCOBACTERIUM TUBERCULOSIS DRUG RESISTANCE MUTATIONS AND UNDERSTANDING OF PK/PD: TREATMENT AND CARE IMPLICATIONS

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-2018-4-6.21 ◽

2019 ◽

Vol 8 (4) ◽

pp. 570

Author(s):

S. K. Heysell ◽

G. Lyles ◽

O. B. Ogarkov

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Resistance Mutations ◽

Drug Resistance Mutations

Download Full-text

Higher Frequency of HIV-1 Drug Resistance and Increased Nucleoside Reverse Transcriptase Inhibitor Mutations among the HIV-1 Positive Antiretroviral Therapy–Naïve patients Coinfected With Mycobacterium tuberculosis Compared With Only HIV Infection in India

Infectious Diseases Research and Treatment ◽

10.1177/1178633718788870 ◽

2018 ◽

Vol 11 ◽

pp. 117863371878887

Author(s):

Sanjeev Sinha ◽

Kartik Gupta ◽

Nawaid Hussain Khan ◽

Dibyakanti Mandal ◽

Mikashmi Kohli ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Antiretroviral Therapy ◽

Reverse Transcriptase ◽

Resistance Mutations ◽

Reverse Transcriptase Inhibitors ◽

Nucleoside Reverse Transcriptase Inhibitors ◽

Drug Resistance Mutations ◽

Group 2 ◽

Hiv 1

Background: Emergence of human immunodeficiency virus (HIV) drug resistance mutations prior to highly active antiretroviral therapy is a serious problem in clinical management of HIV/AIDS. Risk factors for appearance of drug resistance mutations are not known. We hypothesize that Mycobacterium tuberculosis infection may contribute to rapid emergence of such mutations in antiretroviral therapy–naïve patients. Methods: A total of 115 patients were recruited in this study of which 75 were HIV+TB+ coinfected (group 1) and 40 were HIV+TB− (group 2). Blood samples from all the patients were collected and CD4+ cell counts; HIV-1 plasma viral load and sequencing of protease and two-third region of reverse transcriptase of HIV-1 was performed and analyzed for drug resistance pattern. Results: For patients with HIV+TB+, 10.6% (8/75) had mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs), 4% (3/75) to nucleoside reverse transcriptase inhibitors, and only 2.6% (2/75) patients had mutations to protease inhibitors. Interestingly, for group 2 (HIV+TB−), there were only NNRTI mutations found among these patients, and only 3 patients (7.5%) had these drug-resistant mutations. Clade typing and phylogenetic tree analysis showed HIV-1 subtype C predominance in these patients. Conclusions: Our study showed that higher percentage of HIV drug resistance mutations was found among HIV+TB+ individuals compared with tuberculosis-uninfected patients. Tuberculosis coinfection may be a risk factor for emergence of high frequency of drug resistance mutations. Studies with a larger sample size will help to confirm these findings from the Indian population.

Download Full-text