The effect of ubiquitin like protein-proteasome system on the drug resistance of isoniazid mono-resistant mycobacterium tuberculosis

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 1.03μg/mL higher in INH-MTB with PafA over-expression strain than that in INH-MTB. The MIC of isoniazid was 1.03 μg/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.