Porin-like proteins sneak nutrients through Mycobacterium tuberculosis’ waxy defensive walls

Explaining how slow-growing tuberculosis bacteria acquire nutrients across their membranes, without also becoming vulnerable to drugs that target them, researchers report a crucial role in this for a family of porin-like proteins in the bacteria’s notoriously tough, waxy coating. The results provide valuable new insights that could be leveraged in the development of novel tuberculosis drugs.

Mycobacterium tuberculosis

infections – the cause of tuberculosis – are notoriously difficult to treat. The pathogen can be highly resistant to both antibiotic treatments and to the relentless attacks mobilized by the host’s immune system. Like other slow-growing mycobacteria,

M. tuberculosis

are clad in a unique, wax-like outer membrane, which allows the pathogen to persist in the hostile conditions in the human body. Though this armored coating is nigh impenetrable to most small molecules, essential nutrients are still able to slip past the cell’s waxy defenses. How this happens, however, remains enigmatic, but manipulation of channels involved – once identified – could provide a way to enhance the pathogen’s susceptibility to antibiotics. While evaluating a simple molecule particularly effective at killing

M. tuberculosis

, Qinglan Wang and colleagues discovered a unique role of PE/PPE proteins, a large family of abundant mycobacteria-specific proteins associated with the outer envelope of the pathogen and its virulence. PE/PPE proteins have long been considered vital to

M. tuberculosis

virulence, though their function has been enigmatic. Using small molecule inhibitors and genetic manipulation, Wang et al. conclude that several PE/PEE proteins act as pore-like protein, or porins, that ferry vital nutrients across the cell’s waxy wall, allowing

M. tuberculosis

to survive and spread while under antibiotic siege.

###