New Insights in to the Intrinsic and Acquired Drug Resistance Mechanisms in Mycobacteria

Abstract

Infectious diseases caused by clinically important Mycobacteria continue to be an important public health problem worldwide primarily due to emergence of drug resistance crisis. In recent years, the control of tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (MTB), is hampered by the emergence of multidrug resistance (MDR), defined as resistance to at least isoniazid (INH) and rifampicin (RIF), two key drugs in the treatment of the disease. Despite the availability of curative anti-TB therapy, inappropriate and inadequate treatment has allowed MTB to acquire resistance to the most important anti-TB drugs. Likewise, for most mycobacteria other than MTB, the outcome of drug treatment is poor and is likely related to the high levels of antibiotic resistance. Thus, a better knowledge of the underlying mechanisms of drug resistance in mycobacteria could aid not only to select the best therapeutic options but also to develop novel drugs that can overwhelm the existing resistance mechanisms. In this article, we review the distinctive mechanisms of antibiotic resistance in mycobacteria.

Recent updates on drug resistance in Mycobacterium tuberculosis

“…; Nasiri et al . ). The naturally occurring antibiotic fosfomycin is a specific inhibitor of MurA and forms a covalent adduct with a cysteine residue in the active sites.…”

“…; Nasiri et al . ). Proteins of antigen 85 (Ag85) complexes are involved in synthesis of trehalose dimycolate (TDM) which is important for cell wall integrity in Mtb .…”

“…; Nasiri et al . ). Therefore, production of TDM by Ag85 is essential for intrinsic resistance of Mtb .…”

“…; Nasiri et al . ). The two penicillin binding proteins, PonA1 and PonA2, contribute to biosynthesis and homeostasis of cell wall components and ponA2 mutants showed four to eightfold increase in ß‐lactam susceptibility (Smith et al .…”

Disinfectant residuals in drinking water systems select for mycobacterial populations with intrinsic antimicrobial resistance

“…It is often used in combination with rifampicin (i.e., rifamycin derivative) to potentiate bactericidal effects. Resistance traits associated with isoniazid resistance were exclusive to Dis systems at both “stringent” and “medium” sequence similarity threshold and mapped back to a single resistance gene efpA , which is an efflux pump found in mycobacterial species 70 . Fluoroquinolones interfere with DNA replication and transcription as their primary antimicrobial activity mechanisms.…”