Transport mediated antibiotic resistance in Mycobacterium tuberculosis

The incredible complexity of the mycomembrane represents a challenge for antibiotics to penetrate and effectively kill Mycobacterium tuberculosis (M. tb), the causative organism of human tuberculosis (TB).Additionally, intrinsic resistance mechanisms that either degrade or modify antibiotics further reduce the effectiveness of anti-TB drugs. To overcome the problem of permeation, it is important that transport mechanisms across the mycobacterial cell envelope are well understood. Porins required for nutrient uptake are sparsely represented in M. tb, and mutations in porin encoding genes are known to modulate antibiotic susceptibilities in M. tb. Along with the reduction in influx, upregulation of efflux pumps, and mutations leading to their overexpression are frequent in clinical isolates of drug-resistant TB. Since the present treatment strategy involves a lengthy regimen with high dose drug combinations, the study of transport proteins, becomes crucial to developing innovative treatment regimens to significantly improve patient outcomes. This review presents the state-of-art knowledge about transporters that help M. tb maintain nutrient uptake from the host and extrude toxic compounds, including antibiotics. These transporters could not only serve as potential targets to shorten the treatment regimen for drug susceptible TB, but could also be of utility in developing treatments for drug resistant infections.