Novel role of PE_PGRS47 in the alteration of mycobacterial cell wall integrity and drug resistance.

The proline-glutamic acid and proline-proline-glutamic acid (PE/PPE) family of proteins is widespread in pathogenic mycobacteria and plays different roles in mycobacterial physiology. While several PE/PPE family proteins have been studied, the exact function of most PE/PPE proteins in the physiology of Mycobacterium tuberculosis (Mtb) remains unknown. PE_PGRS47 belongs to the PE/PPE family of proteins reported to help Mtb evade protective host immune responses. In this study, we demonstrate a novel role of PE_PGRS47. Heterologous expression of the pe_pgrs47 gene in a non-pathogenic Mycobacterium smegmatis, intrinsically deficient of PE_PGRS protein, exhibits modulated colony morphology and cell wall lipid profile leading to a marked susceptibility to multiple antibiotics and environmental stressors. Using ethidium bromide/Nile red uptake assays, Mycobacterium smegmatis expressing PE_PGRS47 showed higher cell wall permeability than the control strain. Overall, these data suggested that PE_PGRS47 is cell surface exposed and influences cell wall integrity and the formation of mycobacterial colonies, ultimately potentiating the efficacy of lethal stresses against mycobacteria.