The PPE2 protein of Mycobacterium tuberculosis translocates to host nucleus and inhibits nitric oxide production

Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is one of the most successful pathogens of humans. It has evolved several adaptive skills and evasion mechanisms to hijack the immunologically educated host to suit its intracellular lifestyle. Here, we show that one of the unique PPE family member proteins of M. tuberculosis, PPE2, can limit Nitric Oxide (NO) production by inhibiting inos gene transcription. PPE2 protein has a leucine zipper DNA-binding motif and a functional nuclear localization signal. PPE2 was translocated into the macrophage nucleus via the classical importin α/β pathway where it interacted with a GATA-binding site overlapping with the TATA box of inos promoter and inhibited NO production. PPE2 prolonged intracellular survival of a surrogate bacterium M. smegmatis in vitro as well as in vivo. This information is likely to improve our knowledge of host-pathogen interactions during M. tuberculosis infection which is crucial for designing effective anti-TB therapeutics

PE11, a PE/PPE family protein of Mycobacterium tuberculosis is involved in cell wall remodeling and virulence

The role of the unique proline-glutamic acid (PE)/proline-proline-glutamic acid (PPE) family of proteins in the pathophysiology and virulence of Mycobacterium tuberculosis is not clearly understood. One of the PE family proteins, PE11 (LipX or Rv1169c), specific to pathogenic mycobacteria is found to be over-expressed during infection of macrophages and in active TB patients. In this study, we report that M. smegmatis expressing PE11 (Msmeg-PE11) exhibited altered colony morphology and cell wall lipid composition leading to a marked increase in resistance against various environmental stressors and antibiotics. The cell envelope of Msmeg-PE11 also had greater amount of glycolipids and polar lipids. Msmeg-PE11 was found to have better survival rate in infected macrophages. Mice infected with Msmeg-PE11 had higher bacterial load, showed exacerbated organ pathology and mortality. The liver and lung of Msmeg-PE11-infected mice also had higher levels of IL-10, IL-4 and TNF-α cytokines, indicating a potential role of this protein in mycobacterial virulence

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

Autosomal recessive anhidrotic ectodermal dysplasia: A rare entity

We describe a case of anhidrotic ectodermal dysplasia (AED) with an autosomal recessive mode of inheritance, a very rare entity, in a 2-year-old female child of two asymptomatic, consanguineous parents. Their previous child also had a similar condition. Autosomal recessive AED (AR-AED) can have its full expression both in males and females and it is clinically indistinguishable from the x-linked recessive AED (XL-AED), which is the most common type of ectodermal dysplasia. Unlike the partially symptomatic carriers of XL-AED, the heterozygotes of AR-AED are phenotypically asymptomatic

Chronicles of Gerhard-Henrik Armauer Hansen′s life and work

Gerhard-Henrik Armauer Hansen, a Norwegian scientist, discovered Mycobacterium leprae as the causative organism for leprosy, defying the hereditary affliction theory of the disease. He was born in Bergen, Norway in 1841 in a Danish family. After acquiring his medical degree in 1866 from the University of Oslo, he joined as an assistant physician in a leprosy hospital in Bergen. In 1873, he published his report claiming leprosy to be an infectious disease with a description of the infectious material in leprous tissue. His conviction of belief and an unstinted devotion to a lifetime of scientific research changed the way leprosy was approached as a disease. It was the fruit of his untiring work that the amended act of 1885 was passed, which resulted in steady decline in leprosy burden in Norway. In February 1912 he breathed his last, leaving behind an inspirational story of a brave heart scientist who fought all odds to unveil the truth for the benefit of mankind

"Pseudo" nomenclature in dermatology: What′s in a name?

In the bewildering array of scientific nomenclature in the medical field, it is important to use correct terminology, know their aberrations and the reason behind a specific terminology. This paper is an attempt towards compiling all the pseudo-nomenclatures coined in dermatology, in order to make it easier to retain and recollect these pseudo names, signs, morphology, diseases, and conditions. It is also imperative to know the true entities that these pseudo names masquerade as, so as to understand the explanation for assigning the term ′pseudo′ to these conditions. A total of 52 pseudo-terms have been compiled here in reference to dermatology. Most of these pseudo-nomenclatures were coined due to some clinical or histopathological resemblance to the true conditions, while some were premature conclusions drawn from a flawed understanding of the basic nature of the condition. Clear understanding of each of these terms and the explanation behind them being pseudo will enable a dermatologist to avoid misdiagnosis and needless confusion