Detection of katG, inhA and ahpC gene mutation in clinical isolates of isoniazid-resistant Mycobacterium tuberculosis in Makassar City, South Sulawesi, Indonesia

Indian J Tuberc. 2024 Oct;71(4):383-388. doi: 10.1016/j.ijtb.2023.03.019. Epub 2023 Apr 1.

Abstract

Background: Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis (M. tuberculosis). The world is currently facing challenges due to the spread of anti-tuberculosis drug-resistant of M. tuberculosis. Isoniazid-resistant (INH), is one of the first-line anti-tuberculosis agents that has a high resistance case. This study used Multiplex allele-specific Polymerase Chain Reaction (MAS-PCR) to detect the most common mutations associated with isoniazid resistance on inhA, katG, and ahpC gene.

Methods: This study used samples from clinical isolates of M. tuberculosis which had been tested for their antibiotic sensitivity of first-line anti-tuberculosis drugs. The DNA extraction process was carried out using the boiling method and then amplified with specific primers for inhA, katG, and ahpC genes using the MAS-PCR method. The results are then read on the electrophoretic gel with an interpretation of the mutation gene when the target gene DNA bands were absent according to the allele-specific fragments target.

Results: A total of 200 isolates were tested in this study consisting of isoniazid-resistant and susceptible with the largest distribution of Multi-Drug Resistant (MDR) isolates with a total of 146 isolates (73%). The most significant gene mutation was on the ahpC gene in 61 isolates (30,5%) and the combination mutation of the katG + ahpC gene in 52 isolates (26%) with sensitivity and specificity of the test reaching 87% and 42% for the detection of INH-resistant.

Conclusion: Mutation on the ahpC gene has the highest percentage in this study. AhpC gene can be considered one of the essential genes to be tested for the cause of isoniazid-resistant. Using MAS-PCR for detecting gene mutation in isoniazid-resistant was simple and easy, it has the potential to be widely used as a rapid screening molecular test.

Keywords: Gene mutation; Multidrug-resistant; Multiplex PCR; Tuberculosis.

MeSH terms

  • Adult
  • Antitubercular Agents* / pharmacology
  • Antitubercular Agents* / therapeutic use
  • Bacterial Proteins* / genetics
  • Catalase* / genetics
  • Drug Resistance, Multiple, Bacterial / genetics
  • Female
  • Humans
  • Indonesia
  • Isoniazid* / pharmacology
  • Isoniazid* / therapeutic use
  • Male
  • Microbial Sensitivity Tests
  • Multiplex Polymerase Chain Reaction
  • Mutation*
  • Mycobacterium tuberculosis* / drug effects
  • Mycobacterium tuberculosis* / genetics
  • Mycobacterium tuberculosis* / isolation & purification
  • Oxidoreductases / genetics
  • Tuberculosis, Multidrug-Resistant* / microbiology

Substances

  • Isoniazid
  • Antitubercular Agents
  • Bacterial Proteins
  • katG protein, Mycobacterium tuberculosis
  • InhA protein, Mycobacterium
  • Catalase
  • Oxidoreductases