Cell wall biosynthesis and latency during tuberculosis infections

Abstract

Mycobacterium tuberculosis (Mtb) uses a wide range of mechanisms to survive the host immune system. Mtb can persist in host tissues for months to decades without replicating, however, non-replicating (or dormant) Mtb has the ability to resume growth at any time. Persons with latent TB infection do not have typical TB symptoms, and dormant forms of Mtb are not considered transmissible. Several factors (e.g. HIV infection, cancers, and immunosuppressive drug therapy) alter the course of latent TB and are thought to have the potential to cause reactivation, leading to active TB. Treatment regimens for latent TB infection require long durations in order to prevent relapse. It is difficult to eradicate latent forms of the relatively drug resistant Mtb in short periods of time with the currently available TB therapies. Thus, it is very important to develop new drugs for the treatment of latent or persistent forms of Mtb that reduce treatment time required for TB patients. Mycobacterial cell walls consist of complex mixtures of polysaccharides and mycolic acids, and they play an important role in escaping from the host immune systems and in surviving within granulomas that form in response to the bacteria. This chapter reviews the potential drug targets that exist in cell wall biosynthesis for non-replicating (or dormant) Mtb based on bioinformatics, genomic and proteomic analyses and in vitro data with replicating and non-replicating bacilli.