Mycobacterial escape from macrophage phagosomes to the cytoplasm represents an alternate adaptation mechanism.

Shilpa V Jamwal,Archana Singh,Atanu Basu,Kanury V.S Rao,Parul Mehrotra,Zaved Siddiqui

doi:10.1038/srep23089

Abstract

Survival of Mycobacterium tuberculosis (Mtb) within the host macrophage is mediated through pathogen-dependent inhibition of phagosome-lysosome fusion, which enables bacteria to persist within the immature phagosomal compartment. By employing ultrastructural examination of different field isolates supported by biochemical analysis, we found that some of the Mtb strains were in fact poorly adapted for subsistence within endocytic vesicles of infected macrophages. Instead, through a mechanism involving activation of host cytosolic phospholipase A2, these bacteria rapidly escaped from phagosomes, and established residence in the cytoplasm of the host cell. Interestingly, by facilitating an enhanced suppression of host cellular autophagy, this translocation served as an alternate virulence acquisition mechanism. Thus, our studies reveal plasticity in the adaptation strategies employed by Mtb, for survival in the host macrophage.

Highlights

In subsequent experiments we found that rapamycin-dependent activation of autophagy was attenuated to a greater extent in cells infected with either of the cytosol residing Mycobacterium tuberculosis (Mtb) strains, as opposed to those displaying a bias towards endosomal localization (Fig. 4E, Fig. S3)
Our study provides an added perspective to the accumulating support for Mtb translocation from phagosomes to the cytosol of infected macrophages
In some strains, cytosolic translocation was evident within hours after macrophage entry

Summary

Introduction

This is highlighted by the representative high-magnification image for JAL2287 where the continuity of bacterial cell wall with the cytoplasm of lung macrophage is clearly evident, as compared to the situation for the vesicle-enclosed H37Rv (Fig. 2C-(i), C-(ii)). In this context our finding that JAL2287, 2549, and MYC431 bacteria were already localized primarily in the cytoplasm by 24 hr after THP-1 cell infection

Results

Conclusion