Mycobacterium tuberculosis Lineages Associated with Mutations and Drug Resistance in Isolates from India

Shanmugam, Siva Kumar; Kumar, Narender; Tamilzhalagan, Sembulingam; Ramalingam, Suresh Babu; Selvaraj, Ashok; Rajendhiran, Udhayakumar; Solaiyappan, Sudha; Tripathy, Srikanth; Natrajan, Mohan; Padmapriyadarsini, Chandrasekaran; Swaminathan, Soumya; Parkhill, Julian; Peacock, Sharon J.; Ranganathan, Uma Devi

doi:10.1128/spectrum.01594-21

Cited by 15 publications

(15 citation statements)

References 39 publications

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“…Notably, we found geographic disparities in sublineage 1.2.1 isolates mainly found in southern Taiwan, where the majority of migrants live, and none were identified in eastern Taiwan. Phylogenetic analysis showed that drug resistance mutations, RIF rpoB H445Y, was associated with lineage 1, as observed in a previous study 42 ; whereas, RIF rpoB S450L and STR rpsL K43R, were associated with lineage 2, as observed in previous studies 19 , 43 . Higher mutation rates of lineage 2 isolates might account for increased adaptation abilities and drug resistance rates 44 .…”

Section: Discussionsupporting

confidence: 84%

Whole-genome sequencing-based analyses of drug-resistant Mycobacterium tuberculosis from Taiwan

Xiao

Liu

Lin

et al. 2023

Sci Rep

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Drug-resistant tuberculosis (DR-TB) posed challenges to global TB control. Whole-genome sequencing (WGS) is recommended for predicting drug resistance to guide DR-TB treatment and management. Nevertheless, data are lacking in Taiwan. Phenotypic drug susceptibility testing (DST) of 12 anti-TB drugs was performed for 200 Mycobacterium tuberculosis isolates. WGS was performed using the Illumina platform. Drug resistance profiles and lineages were predicted in silico using the Total Genotyping Solution for TB (TGS-TB). Using the phenotypic DST results as a reference, WGS-based prediction demonstrated high concordance rates of isoniazid (95.0%), rifampicin (RIF) (98.0%), pyrazinamide (98.5%) and fluoroquinolones (FQs) (99.5%) and 96.0% to 99.5% for second-line injectable drugs (SLIDs); whereas, lower concordance rates of ethambutol (87.5%), streptomycin (88.0%) and ethionamide (84.0%). Furthermore, minimum inhibitory concentrations confirmed that RIF rpoB S450L, FQs gyrA D94G and SLIDs rrs a1401g conferred high resistance levels. Besides, we identified lineage-associated mutations in lineage 1 (rpoB H445Y and fabG1 c-15t) and predominant lineage 2 (rpoB S450L and rpsL K43R). The WGS-based prediction of drug resistance is highly concordant with phenotypic DST results and can provide comprehensive genetic information to guide DR-TB precision therapies in Taiwan.

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Section: Discussionsupporting

confidence: 84%

Whole-genome sequencing-based analyses of drug-resistant Mycobacterium tuberculosis from Taiwan

Xiao

Liu

Lin

et al. 2023

Sci Rep

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“…The WGS analysis enables a systematic comparison of isolates and the detection of antimicrobial resistance gene mutations. 17,18 Additionally, WGS analysis gives a more accurate judgment compared with MLST analysis alone in this study. MLST analysis uses housekeeping genes, which is independent of the specimen's environment and refers to the specific library of a sequence type.…”

Section: Discussionmentioning

confidence: 68%

Pseudo-outbreak of Mycobacterium lentiflavum at a general hospital in Japan

Nagano

Kuronuma

Kitamura

et al. 2023

Infect. Control Hosp. Epidemiol.

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Background: Mycobacterium lentiflavum is a slow-growing nontuberculous mycobacterium that is widely distributed in soil and water systems, but it is sometimes pathogenic to humans. Although cases of M. lentiflavum infections are rare, 22 isolates of M. lentiflavum were identified at a single hospital in Japan. We suspected a nosocomial outbreak; thus, we conducted transmission pattern and genotype analyses. Methods: Cases of M. lentiflavum isolated at Kushiro City General Hospital in Japan between May 2020 and April 2021 were analyzed. The patient samples and environmental culture specimens underwent whole-genome sequencing (WGS). Additionally, we retrospectively collected clinical data from patient medical records. Results: Altogether, 22 isolates of M. lentiflavum were identified from sputum and bronchoalveolar lavage samples. Clinically, the instances with M. lentiflavum isolates were considered contaminants. In the WGS analysis, 19 specimens, including 18 patient samples and 1 environmental culture from the hospital’s faucet, showed genetic similarity. The frequency of M. lentiflavum isolation decreased after we prohibited the use of taps where M. lentiflavum was isolated. Conclusions: WGS analysis identified that the cause of M. lentiflavum pseudo-outbreak was the water used for patient examinations, including bronchoscopy.

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“…Numerous studies reviewed elsewhere have indicated that L2 and L4 strains are more associated with drug resistance, MDR, and XDR ( Gygli et al., 2017 ; Shanmugam et al., 2022 ). Several studies have demonstrated that L2 Mtb strains acquire drug resistances more rapidly in vitro ( Ford et al., 2013 ), and are also more likely to develop RIF resistance after becoming resistant to INH ( Torres Ortiz et al., 2021 ).…”

Section: Mtb Genetic Variation and Antibiotic Susceptibilitymentioning

confidence: 99%

Mycobacterium tuberculosis functional genetic diversity, altered drug sensitivity, and precision medicine

Stanley

Liu

Fortune

2022

Front. Cell. Infect. Microbiol.

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In the face of the unrelenting global burden of tuberculosis (TB), antibiotics remain our most effective tools to save lives and control the spread of Mycobacterium tuberculosis (Mtb). However, we confront a dual challenge in our use of antibiotics: simplifying and shortening the TB drug regimen while also limiting the emergence and propagation of antibiotic resistance. This task is now more feasible due to the increasing availability of bacterial genomic data at or near the point of care. These resources create an opportunity to envision how integration of bacterial genetic determinants of antibiotic response into treatment algorithms might transform TB care. Historically, Mtb drug resistance studies focused on mutations in genes encoding antibiotic targets and the resulting increases in the minimal inhibitory concentrations (MICs) above a breakpoint value. But recent progress in elucidating the effects of functional genetic diversity in Mtb has revealed various genetic loci that are associated with drug phenotypes such as low-level MIC increases and tolerance which predict the development of resistance and treatment failure. As a result, we are now poised to advance precision medicine approaches in TB treatment. By incorporating information regarding Mtb genetic characteristics into the development of drug regimens, clinical care which tailors antibiotic treatment to maximize the likelihood of success has come into reach.

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Mycobacterium tuberculosis Lineages Associated with Mutations and Drug Resistance in Isolates from India

Abstract: Current knowledge on resistance-conferring determinants in Mycobacterium tuberculosis is biased toward globally dominant lineages 2 and 4. In contrast, lineages 1 and 3 are predominant in India.

Cited by 15 publications

References 39 publications

Whole-genome sequencing-based analyses of drug-resistant Mycobacterium tuberculosis from Taiwan

Whole-genome sequencing-based analyses of drug-resistant Mycobacterium tuberculosis from Taiwan

Pseudo-outbreak of Mycobacterium lentiflavum at a general hospital in Japan

Mycobacterium tuberculosis functional genetic diversity, altered drug sensitivity, and precision medicine

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