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Abstract
Background: Tuberculosis (TB) is one of the most widespread and lethal infectious diseases worldwide. The emergence of drugresistant TB has hampered effective TB treatment and control. Prokaryotic ubiquitin-like Protein-Proteasome System (PPS) contributes to the survival of Mycobacterium tuberculosis in the host. However, whether PPS effects drug resistance of isoniazid monoresistant Mycobacterium tuberculosis (INH-MTB) is still unknown.
Objectives: This study aimed at exploring the effect of PPS on drug resistance of INH-MTB strain.
Methods: In this study, over-expression of strains and deletion of mutant strains were constructed using electroporation. The researchers identified these constructed strains by Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR) or PCR. The Minimum Inhibitory Concentration (MIC) of isoniazid in INH-MTB strain and its derivative PPS mutant strains were determined using the Resazurin micro-titre assay.
Results: The MIC of isoniazid was 8 µg/mL higher in INH-MTB with Pup over-expression strain than that in INH-MTB. The MIC of isoniazid was 4.82 µg/mL, 4.98 µg/mL, 4.99 µg/mL, and 4.9 µg/mL lower in INH-MTB with deletion of Pup, Dop, PafA or Mpa strains than that in INH-MTB, respectively. The differences had statistical significance (P< 0.05). The MIC of isoniazid was 1.03 µg/mL higher in INH-MTB with PafA over-expression strain than that in INH-MTB. The MIC of isoniazid was 1.03 ^g/mL and 0.68 µg/mL lower in INH-MTB with Dop, Mpa over-expression strains than that in INH-MTB, respectively. The differences had no statistical significance (P > 0.05).
Conclusions: These results show that PPS effects the drug resistance of the INH-MTB strain.
Keywords: Isoniazid, Drug Resistance, Mycobacterium Tuberculosis, Pup
1. Background
Tuberculosis (TB) is a top infectious killer worldwide, and is responsible for more deaths than human immunodeficiency virus (HIV) and malaria, resulting in 400,000 deaths, annually. In 2016, the world health organization (WHO) estimated that 580 000 people worldwide develop Multidrug-Resistant (MDR) TB. India, China, and the Russian Federation accounted for 45% of the 580 000 cases. Although isoniazid (INH) is an essential element of all firstline treatment regimens for TB (1), INH resistance is an obstacle to the treatment of TB (2,3). In order to achieve the ambitious target set in the End TB Strategy, these highest TB burden countries need to depend on advances in TB prevention and care.
According to broad analyses, mutations...