The ATP-Binding Cassette (ABC) Transport Systems in Mycobacterium tuberculosis: Structure, Function, and Possible Targets for Therapeutics

SIMPLE SUMMARY: Mycobacterium tuberculosis is a bacterium of great medical importance because it causes tuberculosis, a disease that affects millions of people worldwide. Two important features are related to this bacterium: its ability to infect and survive inside the host, minimizing the immune response, and the burden of clinical isolates that are highly resistant to antibiotics treatment. These two phenomena are directly affected by cell envelope proteins, such as proteins from the ATP-Binding Cassette (ABC transporters) superfamily. In this review, we have compiled information on all the M. tuberculosis ABC transporters described so far, both from a functional and structural point of view, and show their relevance for the bacillus and the potential targets for studies aiming to control the microorganism and structural features. ABSTRACT: Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), a disease that affects millions of people in the world and that is associated with several human diseases. The bacillus is highly adapted to infect and survive inside the host, mainly because of its cellular envelope plasticity, which can be modulated to adapt to an unfriendly host environment; to manipulate the host immune response; and to resist therapeutic treatment, increasing in this way the drug resistance of TB. The superfamily of ATP-Binding Cassette (ABC) transporters are integral membrane proteins that include both importers and exporters. Both types share a similar structural organization, yet only importers have a periplasmic substrate-binding domain, which is essential for substrate uptake and transport. ABC transporter-type importers play an important role in the bacillus physiology through the transport of several substrates that will interfere with nutrition, pathogenesis, and virulence. Equally relevant, exporters have been involved in cell detoxification, nutrient recycling, and antibiotics and drug efflux, largely affecting the survival and development of multiple drug-resistant strains. Here, we review known ABC transporters from M. tuberculosis, with particular focus on the diversity of their structural features and relevance in infection and drug resistance.