Genome-wide analysis of the host intracellular network that regulates survival of Mycobacterium tuberculosis.
We performed a genome-wide siRNA screen to identify host factors that regulated pathogen load in human macrophages infected with a virulent strain of Mycobacterium tuberculosis. Iterative rounds of confirmation, followed by validation, identified 275 such molecules that were all found to functionally associate with each other through a dense network of interactions. This network then yielded to a molecular description of the host cell functional modules that were both engaged and perturbed by the pathogen. Importantly, a subscreen against a panel of field isolates revealed that the molecular composition of the host interface varied with both genotype and the phenotypic properties of the pathogen. An analysis of these differences, however, permitted identification of those host factors that were invariantly involved, regardless of the diversification in adaptive mechanisms employed by the pathogen. Interestingly, these factors were found to predominantly function through the regulation of autophagy.
Kumar
Dhiraj
D
Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Nath
Lekha
L
Kamal
Md Azhar
MA
Varshney
Ankur
A
Jain
Avinash
A
Singh
Sarman
S
Rao
Kanury V S
KV
D015894:Genome, Human; D055106:Genome-Wide Association Study; D015698:Genomic Library; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D050296:Microbial Viability; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics
D034741:RNA, Small Interfering