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Intracellular growth and survival of Salmonella enterica serovar Typhimurium carrying truncated hemoglobins of Mycobacterium tuberculosis.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Intracellular growth and survival of Salmonella enterica serovar Typhimurium carrying truncated hemoglobins of Mycobacterium tuberculosis.
 
Creator Pawaria, Sudesh
Rajamohan, Govindan
Gambhir, Vandana
Lama, Amrita
Varshney, Grish C
Dikshit, Kanak L
 
Subject QR Microbiology
 
Description Two distantly related truncated hemoglobins (trHbs), HbN and HbO, are produced at different growth stages of Mycobacterium tuberculosis. Oxygen and nitric oxide (NO) binding properties of these trHbs suggest their vital role(s) in adaptation of tubercle bacillus under hypoxic and nitrosative stress conditions. Here, we have demonstrated that HbN of M. tuberculosis provides distinct advantage over HbO in supporting intracellular growth and survival of the heterologous host, Salmonella enterica serovar Typhimurium, during macrophage infection specifically against toxicity of NO. HbN and HbO encoding genes of M. tuberculosis have been expressed in a NO-sensitive hmp mutant of S. enterica serovar Typhimurium that exhibits attenuated growth within the macrophages. Presence of HbN and HbO conferred distinct oxygen dependent NO metabolizing activity to the mutant S. enterica serovar Typhimurium. However, the HbN carrying cells exhibited nearly 2-3-fold higher NO metabolizing activity than the isogenic strain having HbO under aerobic condition. More than half of the NO uptake activity of HbN carrying cells was retained when oxygen level dropped to microaerobic condition. In comparison, NO uptake activity of HbO carrying cells of mutant S. enterica dropped drastically (90%) under similar hypoxic conditions. When internalized by mice peritoneal macrophages, HbN carrying cells exhibited 3- and 4-fold higher survival compared to similarly bound and internalized HbO carrying and control cells, respectively. The protective effect of HbN persisted even after activation of macrophages in the presence of IFN-gamma, whereas, HbO did not show any significant effect on survival of the NO-sensitive hmp mutant of Salmonella. These results provide strong experimental evidence in support of the protective role of HbN against nitrosative stress inside macrophages and suggest that intracellular protection conferred by HbN of M. tuberculosis might not be restricted to its native host only.
 
Publisher Elsevier Science
 
Date 2007-04
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/1009/1/dikshit2007.pdf
Pawaria, Sudesh and Rajamohan, Govindan and Gambhir, Vandana and Lama, Amrita and Varshney, Grish C and Dikshit, Kanak L (2007) Intracellular growth and survival of Salmonella enterica serovar Typhimurium carrying truncated hemoglobins of Mycobacterium tuberculosis. Microbial pathogenesis, 42 (4). pp. 119-28. ISSN 0882-4010
 
Relation http://www.sciencedirect.com/science/article/pii/S0882401006001641
http://crdd.osdd.net/open/1009/