Drug Susceptibility and Mutation Profiles in Mycobacterium tuberculosis Isolates from a Tertiary Care Hospital in Kerala, India

Parasmal Suresh Amrita Center for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India;

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Swathy Thulasidharan Department of Microbiology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India;

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Anil Kumar Department of Microbiology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India;

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Sunisha Sunil Amrita Center for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India;

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Maria Roy Amrita Center for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India;

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Varsha P. Ramesh Amrita Center for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India;

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Raja Biswas Amrita Center for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India;

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Akhilesh Kunoor Respiratory Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India

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Lalitha Biswas Amrita Center for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India;

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ABSTRACT.

The rising prevalence of drug-resistant Mycobacterium tuberculosis (MTB) strains poses a significant challenge to global tuberculosis (TB) control efforts. This study aimed to analyze drug resistance patterns and investigate the molecular characteristics of 193 MTB clinical isolates to shed light on the mechanisms of drug resistance. Of the 193 MTB clinical isolates, 28.5% (n = 53) exhibited mono-drug or multidrug resistance. Pyrazinamide mono-drug resistance (PZAr) was the most prevalent (17%, n = 33), followed by isoniazid mono-drug resistance (3.6%, n = 7). Rifampicin resistance was associated with mutations in the rpoB gene (D435Y, D435V, S450L, L452P). Isoniazid resistance mutations were found in the katG (S315T), inhA (C[-15] T), and ndh (R268H) genes, whereas ethambutol resistance mutations were observed in the embB gene (M306V, M306I, M306L, G406S, Q497R). Surprisingly, 94% of PZAr isolates (n = 31) showed no mutations in the pncA or rpsA genes. The presence of the R268H mutation in the ndh gene, not previously linked to PZAr, was detected in 15% of PZAr isolates (n = 5), suggesting its potential contribution to PZAr in specific cases but not as a predominant mechanism. The specific molecular mechanisms underlying PZAr in the majority of the isolates remain unknown, emphasizing the need for further research to uncover the contributing factors. These findings contribute to the understanding of drug resistance patterns and can guide future efforts in TB control and management.

Author Notes

Financial support: This work was supported by the Kerala Biotechnology Commission (047/YIPB/KBC/2017/KSCSTE) to L. Biswas as Principal Investigator.

Authors’ contributions: P. Suresh: Data curation, formal analysis, investigation; S. Thulasidharan: Data curation, formal analysis, investigation; A. Kumar: Resources, project administration, supervision, investigation, data curation, formal analysis, writing (review and editing); S. Sunil: Data curation, formal analysis, investigation; M. Roy: Data curation, formal analysis, investigation; V. P. Ramesh: Data curation, formal analysis, investigation; R. Biswas: Resources, investigation, writing (review and editing); A. Kunoor: Resources, analysis, investigation; L. Biswas: Conceptualization, resources, project administration, supervision, validation, investigation, data curation, formal analysis, writing (original draft).

Authors’ addresses: Parasmal Suresh, Amrita Center for Nanosciences and Molecular medicine, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, Kerala, India, E-mail: parasmals@aims.amrita.edu. Sunisha Sunil, Amrita Center for Nanosciences and Molecular medicine, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, Kerala, India, E-mail: sunisha.sunil11@gmail.com. Maria Roy, Amrita Center for Nanosciences and Molecular medicine, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, Kerala, India, E-mail: maria.roy.bio@gmail.com. Varsha P Ramesh Amrita Center for Nanosciences and Molecular medicine, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, Kerala, India, E-mail: varsharamesh1898@gmail.com. Raja Biswas Amrita Center for Nanosciences and Molecular medicine, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, Kerala, India, E-mail: rajabiswas@aims.amrita.edu. Lalitha Biswas, Amrita Center for Nanosciences and Molecular medicine, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, Kerala, India, E-mail: lalithabiswas@aims.amrita.edu. Swathy Thulasidharan, Department of Microbiology Amrita Institute of Medical Sciences & Research Centre,Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, Kerala, India, E-mail: swathy.thulasidharan@gmail.com. Anil Kumar, Department of Microbiology Amrita Institute of Medical Sciences & Research Centre,Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, Kerala, India, E-mail: vanilkumar@aims.amrita.edu. Akhilesh Kunoor, Department of Respiratory Medicine, Amrita Institute of Medical Sciences & Research Centre, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, Kerala, India, Email: akhileshk@aims.amrita.edu.

Address correspondence to Anil Kumar, Department of Microbiology, Amrita Institute of Medical Sciences & Research Centre, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi 682041, Kerala, India, Email: vanilkumar@aims.amrita.edu or Lalitha Biswas, Amrita Center for Nanosciences and Molecular medicine, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi 682041, Kerala, India, Email: lalithabiswas@aims.amrita.edu
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