The NRAMP1 gene codes for the 'natural resistance associated macrophage protein' , belonging to a family of divalent metal transporters that play important roles in the homeostasis of iron and other metals. Though the exact mechanism of action of this protein is not known, it is implicated in the control of growth of intracellular pathogens. Gruenheid et al  established that the Nramp1 protein which is recruited to the membrane of the endocytic compartments in resting macrophages, is routed to the membranes of phagosomes upon phagocytosis, thereby controlling the replication of intracellular pathogens by altering the intra-vacuolar environment of the microbe-containing phagosome.
Hackam et al  , in their studies with Mycobacterium bovis demonstrated that the pH of phagosomes containing live bacilli was significantly more acidic in Nramp1- expressing macrophages than in mutant cells. These authors suggest that Nramp1 affects intracellular mycobacterial replication by modulating the phagosomal pH implicating a central role for Nramp1 in this process. Others  ,  propose that Nramp1 affects the intra phagosomal microbial replication by modulating iron levels and other divalent cations in this organelle, in the milieu of which both mammalian and bacterial transporters may compete for the same substrate.
In the majority of humans, an effective immune response develops after infection with M. In the remaining percentage of individuals, there appears to be a complex interaction of genetic and environmental factors that probably influences the outcome of an infection. The correlation between Nramp1 gene variations and disease susceptibility points to this gene as a strong candidate for human tuberculosis.
Susceptibility to infection in inbred strains of mice correlated with NRAMP1 mutations with single glycine-to-aspartic acid substitution at position of the predicted trans membrane domain 4 of the Nramp  protein. Further, this genetic predisposition was evident as a dominant trait among the members of a single large aboriginal family in Canada,  an observation that came into light during an epidemic of tuberculosis that occurred in a community of Aboriginal Canadians during the period As mentioned earlier, Nramp1 are found in several systems including bacteria.
The Nramp1 protein homologue in mycobacteria referred to as MRamp is found in M. Further, it is thought to add to those mechanisms that inhibit the acidification of the phagosomes thereby permitting the multiplication of intracellular mycobacteria. A competition thus ensues between the host NRAmp1 and the mycobacterial Mramp in controlling the pH of the phagosome, the outcome of which probably depends on the efficiency of the two transporters.
Toll-like receptors and CpGs Host defense consists of two types of immune responses, innate and adaptive immunity. B and T lymphocytes invoke the adaptive immune response, while the innate immunity is mainly mediated by the macrophages and dendritic cells. Mycobacterium bovis BCG, an attenuated form of M. Today, BCG is a widely used effective treatment of bladder cancer due to its immunogenic activity.
An interesting observation about the active component of BCG that was responsible for enhancing the innate immunity of the host was in fact, the DNA itself. Among these receptors, there were motifs called pathogen associated molecular patterns PAMPs on bacteria and viruses.
TLR signaling pathways, first identified in Drosophila system has been shown to play significant roles in host defense. Pathogenic mycoabcteria including M. These authors suggest that part of the survival strategy of M. It is thought that CD14 ligands present in the cell walls of Gram positive and Gram negative bacteria, which activates TLR signaling resulting in significant antimicrobial responses, may in fact be seen with M.
One of the most successful pathogens has been M. There is thus a great need to understand how exactly the pathogen survives under the in vivo conditions and identify pathways unique to the intracellular environment that could be utilized for the development of new and better drugs. Yet, it is clear that the disease progression is not just related to exposure to the pathogen. The great variability in the susceptibility among persons emphasizes the need for a better understanding of the genetic susceptibility of the host population to this dreaded disease.
The combination of the pathogen's adaptation to new challenges and the susceptibility of specific population makes this a formidable pathogen to fight. However, the fight has to continue with man attempting to control this pathogen, if not to eradicate it altogether. Global burden of tuberculosis. Estimated incidence, prevalence and mortality by country. JAMA ; Webb V, Davies J. Antibiotics and antibiotic resistance. In: Mycobacteria: Molecular biology and Virulence.
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An ideR mutant of Mycobacterium smegmatis has derepressed siderophore production and an altered oxidative stress response. Dussurget O, Smith I. Interdependence of mycobacterial iron regulation, oxidative stress response and isoniazid resistance. Trends Microbiol ; 6: Attenuation of virulence in Mycobacterium tuberculosis expressing a constitutively active iron repressor.
Iron transport in Mycobacterium smegmatis: occurrence of iron-regulated envelope proteins as potential receptors for iron uptake.
J Gen Microbiol ; Sritharan M, Ratledge C. Co-ordinated expression of the components of iron transport mycobactin, exochelin and envelope proteins in Mycobacterium neoaurum. Macrophage-internalized M. Tuberculosis has existed throughout history, but the name has changed frequently over time. In , though, the history of tuberculosis started to take shape into what is known of it today; as the physician Benjamin Marten described in his A Theory of Consumption , tuberculosis may be caused by small living creatures transmitted through the air to other patients.
The BCG vaccine , which was derived from M. From Wikipedia, the free encyclopedia. This article is about the bacterium. For the infection, see tuberculosis. Species of bacterium. See also: Antimicrobial resistance. This section needs expansion. You can help by adding to it. November Main article: History of tuberculosis.
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Bibcode : PLoSO Nature Reviews. PLoS Pathogens. Bibcode : PNAS.. Nature Communications. Bibcode : NatCo Science Advances. Trends in Microbiology. Bulletin of the World Health Organization. Seminars in Immunology. Nobel Foundation. Retrieved 18 November Archived from the original on 21 June Retrieved 18 June Gram-positive bacterial infection : Actinobacteria primarily A00—A79 , —, — Actinomyces israelii Actinomycosis Cutaneous actinomycosis Tropheryma whipplei Whipple's disease Arcanobacterium haemolyticum Arcanobacterium haemolyticum infection Actinomyces gerencseriae.
Propionibacterium acnes. Leprosy : Tuberculoid leprosy Borderline tuberculoid leprosy Borderline leprosy Borderline lepromatous leprosy Lepromatous leprosy Histoid leprosy. Corynebacterium diphtheriae Diphtheria Corynebacterium minutissimum Erythrasma Corynebacterium jeikeium Group JK corynebacterium sepsis.
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