The PPE2 protein of Mycobacterium tuberculosis is secreted during infection and facilitates mycobacterial survival inside the host.

Mycobacterium tuberculosis secrets various effector proteins to evade host immune responses for facilitating its intracellular survival. The bacterial genome encodes several unique PE/PPE family proteins, which have been implicated to play important role in mycobacterial pathogenesis. A member of this family, PPE2 have been shown to contain a monopartite nuclear localization signal (NLS) and a DNA binding domain. In this study, we demonstrate that PPE2 protein is present in the sera of mice infected with either M. smegmatis expressing PPE2 or a clinical strain of M. tuberculosis (CDC1551). It was found that exogenously added PPE2 can permeate through the macrophage cell membrane and eventually translocate into the nucleus which requires the presence of NLS which showed considerable homology to HIV-tat like cell permeable peptides. Exogenously added PPE2 could inhibit NO production and decreased mycobacterial survival in macrophages. PPE2-null mutant of M. tuberculosis failed to inhibit NO production and had poor survival in macrophages which could be rescued by complementation with full-length PPE2. PPE2-null mutants also had poor survival in the lungs of infected mice indicating that PPE2 even when present in the bloodstream can confer a survival advantage to mycobacteria.

The cause-effect relation of tuberculosis on incidence of diabetes mellitus.

Tuberculosis (TB) is one of the oldest human diseases and is one of the major causes of mortality and morbidity across the Globe. Mycobacterium tuberculosis (Mtb), the causal agent of TB is one of the most successful pathogens known to mankind. Malnutrition, smoking, co-infection with other pathogens like human immunodeficiency virus (HIV), or conditions like diabetes further aggravate the tuberculosis pathogenesis. The association between type 2 diabetes mellitus (DM) and tuberculosis is well known and the immune-metabolic changes during diabetes are known to cause increased susceptibility to tuberculosis. Many epidemiological studies suggest the occurrence of hyperglycemia during active TB leading to impaired glucose tolerance and insulin resistance. However, the mechanisms underlying these effects is not well understood. In this review, we have described possible causal factors like inflammation, host metabolic changes triggered by tuberculosis that could contribute to the development of insulin resistance and type 2 diabetes. We have also discussed therapeutic management of type 2 diabetes during TB, which may help in designing future strategies to cope with TB-DM cases.

Secretory proteins of Mycobacterium tuberculosis and their roles in modulation of host immune responses: focus on therapeutic targets.

Mycobacterium tuberculosis, the bacterium responsible for tuberculosis, is one of the most successful pathogens in human history. An extremely resilient cell wall and highly evolved and coordinated strategies for immune evasion have made it a very formidable pathogen. The secretory proteins of M. tuberculosis play a crucial role in its virulence and immune evasion. The secretory proteins are secreted through tightly regulated secretion systems and modulate the host immune responses through a plethora of strategies, including epigenetic reprogramming of infected cells, targeting antigen presentation, inhibition of phagosomal maturation, modulation of cytokine production, apoptosis and redox regulation, etc. Upon infection, the secretory proteins become localized into various cellular organelles, such as nucleus, cytoplasm, phagosomes and Golgi, bodies and hijack the host machineries through their wide gamut of functions, including kinase, phosphatase, methyl transferase activities and interaction with several host partners. In this review, we discuss the secretion systems, the functions of various secretory proteins of M. tuberculosis and their roles in modulating immune responses of the host. We also discuss the feasibility of their use as possible therapeutic targets. This information is likely to improve our understanding of the host-pathogen interaction and help in the design of effective anti-tuberculosis therapeutics.