Potential of Ca2+ in Mycobacterium tuberculosis H37Rv Pathogenesis and Survival

Abstract

The host-pathogen interaction and involvement of calcium (Ca) signaling in tuberculosis infection is crucial and plays a significant role in pathogenesis. Ca is known as a ubiquitous second messenger that could control multiple processes and is included in cellular activities like division, motility, stress response, and signaling. However, Ca is thought to be a regulative molecule in terms of TB infection but its binding relation with proteins/substrates molecules which are influenced with Ca concentrations in host-pathogen interaction requires attention. So, in this review, our primary goal is to focus on some Ca substrates/proteins and their imperative involvement in pathogenesis, which is unclear. We have discussed several Ca-binding substrate and protein that affect intracellular mechanism of infected host cell. The major involvement of these proteins/substrates including calmodulin (CaM), calpain, annexin, surfactant protein A (SP-A), surfactant protein D (SP-D), calprotectin (MRP8/14), and PE_PGRS family protein are considered to be significant; however, their detailed understanding in mycobacterium infection is limited. In this aspect, this study will help in adding up our understanding in TB biology and additionally in the development of new therapeutic approach to reduce TB pandemic worldwide.

MicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy

“…Ca 2+ is known to play a crucial role in TB pathogenesis. The ability of Mtb to manipulate Ca 2+ signaling to prevent phagosome maturation and phagosome–lysosome fusion has been extensively studied 54 – 56 , but the exact role of Ca 2+ signaling in the regulation of autophagy during Mtb infection remains unknown. We found that a Ca 2+ blockade by specific inhibitors markedly reduced autophagosome formation and was accompanied by a higher bacterial load of Mtb , suggesting an essential role of Ca 2+ in autophagy and intracellular survival of Mtb .…”

Molecular Basis Underlying Host Immunity Subversion by Mycobacterium tuberculosis PE/PPE Family Molecules

“…The calcium (Ca 2+ ) signaling is involved in TB infection and plays an important role in the pathogenesis of MTB. The interaction of MTB H37Rv with macrophage alters Ca 2+ signaling, resulting in abnormal phagosome maturation during infection (Sharma and Meena, 2017). Ca 2+ signaling is crucial for the maturation of phagosomes that contains mycobacteria.…”

“…In the host-pathogen interaction and the initial nonspecific attachment of MTB H37Rv with the alveolar macrophage of host, the Ca 2+ concentration suddenly decreased owing to the Ca 2+ -dependent PE_PGRS family proteins. This finally hinders the phagolysosome fusion by decreasing the cytosolic Ca 2+ level in macrophages, contributing to bacillary survival (Yeruva et al, 2016;Sharma and Meena, 2017).…”

“…Saini et al (2016) demonstrated that the DPE_PGRS47 deletion mutant of Mtb exhibited an increased acidification and lysosomal fusion of phagosomes during infection of phagocytic cells. The other PE_PGRS family proteins that modulate the phagosome maturation by Ca 2+ signaling are mentioned in ''PE/PPE Proteins Have Ca 2+ Binding Property that Mediate Host-Pathogen Interaction'' section (Yeruva et al, 2016;Sharma and Meena, 2017).…”

Vitamin D Supplementation in Tuberculosis Patients: A Cross Sectional Study

“…Calcium signaling in tuberculosis infection plays a significant role in the pathogenesis of TB (Sharma, 2017). Calcium also is known as a ubiquitous second messenger that could control multiple processes and is included in cellular activities like division, motility, stress response, and signaling.…”