title: Inhibition of bfl-1/A1 by siRNA inhibits mycobacterial growth in THP-1 cells by enhancing phagosomal acidification.
creator: Dhiman, Rohan
creator: Kathania, Mahesh
creator: Raje, Manoj
creator: Majumdar, Sekhar
subject: QD Chemistry
description: Virulent tubercle bacilli inhibit apoptosis to establish a safe environment within the host cells. Here, we report that NF-kappaB dependent antiapoptotic protein bfl-1/A1 plays an important role in this process. Both virulent and avirulent mycobacteria bearing THP-1 cells expressed considerable amount of bfl-1/A1 after 4 h of infection. However, after 48 h of infection, bfl-1/A1 expression was evident only in Mycobacterium tuberculosis H37Rv but not in M. tuberculosis H37Ra infected cells. When parallel experiments were performed with Human monocyte-derived macrophages (MDMs), differential expression of bfl-1/A1 mRNA was observed in case of M. tuberculosis H37Rv and M. tuberculosis H37Ra infection. siRNA mediated inhibition of bfl-1/A1 induced apoptosis in M. tuberculosis H37Rv infected THP-1 and MDMs. Reduction in intracellular mycobacterial growth was observed in bfl-1/A1 siRNA transfected, M. tuberculosis H37Rv infected THP-1 cells. Enhancement of phagosome-lysosome fusion was observed in bfl-1/A1 siRNA treated and M. tuberculosis H37Rv infected THP-1 cells. These results clearly indicated that differential expression of bfl-1/A1 in M. tuberculosis H37Rv and M. tuberculosis H37Ra infected THP-1 cells probably account for the difference in infection outcome.
publisher: Elsevier Science
date: 2008-04
type: Article
type: PeerReviewed
format: application/pdf
identifier: http://crdd.osdd.net/open/617/1/sekhar08.pdf
relation: http://www.sciencedirect.com/science/article/pii/S0304416507002978
identifier:   Dhiman, Rohan and Kathania, Mahesh and Raje, Manoj and Majumdar, Sekhar  (2008) Inhibition of bfl-1/A1 by siRNA inhibits mycobacterial growth in THP-1 cells by enhancing phagosomal acidification.  Biochimica et biophysica acta, 1780 (4).  pp. 733-42.  ISSN 0006-3002     
relation: http://crdd.osdd.net/open/617/