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Truncated hemoglobin, HbN, is post-translationally modified in Mycobacterium tuberculosis and modulates host-pathogen interactions during intracellular infection.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Truncated hemoglobin, HbN, is post-translationally modified in Mycobacterium tuberculosis and modulates host-pathogen interactions during intracellular infection.
 
Creator Arya, Swati
Sethi, Deepti
Singh, Sandeep
Hade, Mangesh Dattu
Singh, Vijender
Raju, Preeti
Chodisetti, Sathi Babu
Verma, Deepshikha
Varshney, Grish C
Agrewala, J N
Dikshit, Kanak L
 
Description Mycobacterium tuberculosis (Mtb) is a phenomenally successful human pathogen having evolved mechanisms that allow it to survive within the hazardous environment of macrophages and establish long term, persistent infection in the host against the control of cell-mediated immunity. One such mechanism is mediated by the truncated hemoglobin, HbN, of Mtb that displays a potent O2-dependent nitric oxide dioxygenase activity and protects its host from the toxicity of macrophage-generated nitric oxide (NO). Here we demonstrate for the first time that HbN is post-translationally modified by glycosylation in Mtb and remains localized on the cell membrane and the cell wall. The glycan linkage in the HbN was identified as mannose. The elevated expression of HbN in Mtb and M. smegmatis facilitated their entry within the macrophages as compared with isogenic control cells, and mutation in the glycan linkage of HbN disrupted this effect. Additionally, HbN-expressing cells exhibited higher survival within the THP-1 and mouse peritoneal macrophages, simultaneously increasing the intracellular level of proinflammatory cytokines IL-6 and TNF-α and suppressing the expression of co-stimulatory surface markers CD80 and CD86. These results, thus, suggest the involvement of HbN in modulating the host-pathogen interactions and immune system of the host apart from protecting the bacilli from nitrosative stress inside the activated macrophages, consequently driving cells toward increased infectivity and intracellular survival.
 
Publisher Baltimore, MD : American Society for Biochemistry and Molecular Biology
 
Date 2013-10-11
 
Type Article
PeerReviewed
 
Relation http://www.jbc.org/content/288/41/29987.long
http://crdd.osdd.net/open/1619/
 
Identifier Arya, Swati and Sethi, Deepti and Singh, Sandeep and Hade, Mangesh Dattu and Singh, Vijender and Raju, Preeti and Chodisetti, Sathi Babu and Verma, Deepshikha and Varshney, Grish C and Agrewala, J N and Dikshit, Kanak L (2013) Truncated hemoglobin, HbN, is post-translationally modified in Mycobacterium tuberculosis and modulates host-pathogen interactions during intracellular infection. The Journal of biological chemistry, 288 (41). pp. 29987-99. ISSN 1083-351X