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 1.03 µg/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.

Exotoxins secreted byClostridium septicuminduce macrophage death:implications for bacterial immune evasion mechanisms at infection sites

“…However, our data suggest that exposure of mouse peritoneal macrophages to C. septicum PPF≥100 kDa can trigger a cell response, including induction of TNFα and IL-10 expression (D.-L. Zhang et al 2017). Analysis of TNF-α and IL-10 was performed as part of a larger analysis of cytokines secreted by macrophages in response to the toxins contained in the PPF≥100 kDa.…”

“…It has been reported that these cytokines induce autophagy and apoptosis in macrophages (Djavaheri-Mergny et al 2006;Xu et al 2006); however, the mechanism remains to be fully understood. However, our data suggest that exposure of mouse peritoneal macrophages to C. septicum PPF≥100 kDa can trigger a cell response, including induction of TNFα and IL-10 expression (D.-L. Zhang et al 2017). Analysis of TNF-α and IL-10 was performed as part of a larger analysis of cytokines secreted by macrophages in response to the toxins contained in the PPF≥100 kDa.…”