Mycobacterial Small Heat Shock Proteins: Dissecting Their Roles in Pathogenesis and Development of Therapeutics

Small heat shock proteins are a ubiquitous family of molecular chaperones. This class of proteins has a conserved α-crystallin domain. Mycobacterium tuberculosis, the etiological agent that causes tuberculosis (TB), harbors two α-crystallin-related (Acr) small heat shock proteins, Acr1 (Hsp16.3) and Acr2 (HrpA). Both of these proteins have been reported as crucial for the survival and pathogenesis of M. tuberculosis inside the host. Acr1 often plays a critical role in the pathogen's survival in the latent stage, while Acr2 overexpresses following phagocytosis during the active infection and is also required for pathogenesis. The strong immunogenicity of Acr1 and Acr2 has been utilized for developing and boosting vaccines and as a diagnostic marker for active and latent TB. Some recent studies have also implicated the development of drugs against these small heat shock proteins. In addition, several structure-function studies established the role of different stresses on the structure and function of these proteins. However, such studies on Acr2 are few in the literature. In this review, the various biophysical and early diagnostic studies of Acr1 and Acr2 are presented systematically. Subsequently, the role of these Acrs in pathogenesis and toward the development of vaccines against TB is discussed.