Project Details
Projekt
Molecular mechanisms of cell wall homeostasis in Mycobacterium tuberculosis: Significance for host cell adaptation and virulence
Subject Area
Parasitology and Biology of Tropical Infectious Disease Pathogens
Term
from 2014 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 259238682
Tuberculosis remains the infectious disease, caused by a single bacterial pathogen, with the highest prevalence, incidence and mortality worldwide. Approximately one third of the worlds population is latently infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. In 2010 tuberculosis claimed 1.45 Million deaths among people afflicted with M. tuberculosis infection. A growing number of multi drug resistant (MDR) - and extremely drug resistant (XDR) - M. tuberculosis strains elicits a new epidemiological problem. M. tuberculosis is a facultative intracellular pathogen, the primary habitat of which lies within the phagosome of infected alveolar macrophages. Thus it is essential for the pathogen to adapt to the intracellular niche and to modulate the intraphagosomal milieu as well as the hosts immune response in order to render intracellular persistence and replication possible. Therefore, genes, the expression of which is either increased or attenuated in the intracellular habitat, play an essential role during the course of infection. Recently, we were able to identify for the first time genes among 17 strains of the M. tuberculosis complex, which were regulated universally within the macrophage thus implicating an outstanding role for the virulence of the pathogen. We selected genes with a putative implication for cell wall metabolism which will be deleted by site directed mutagenesis in order to elucidate their function and significance for M. tuberculosis infection. Our aim is to decipher essential virulence- and survival strategies of M. tuberculosis for the sake of contributing to identification of possible new targets for antimycobacterial therapy.
DFG Programme
Research Grants
Participating Persons
Dr. Nicolas Gisch; Professor Dr. Otto Holst; Privatdozent Dr. Dominik Schwudke
