Monday, January 14, 2008

GroEL/Tuberculosis Connection?

Interestingly, Mycobacteria encode two GroEL paralogs, known as GroEL1 and GroEL2. The latter is essential, while the former is nonessential and contains the attB site for phage Bxb1 integration. According to Ojha et al., GroEL1 modulates synthesis of mycolates (the long-chain fatty acid components of the mycobacterial cell wall) during biofilm formation and physically associates with KasA, a key component of the type II Fatty Acid Synthase involved in mycolic acid synthesis. These functionalities are pretty far removed from what most would consider typical GroEL functionality.

It turns out that
inactivation of the Mycobacterium smegmatis GroEL1 gene by phage Bxb1 integration prevents the formation of mature biofilms. This is potentially significant since Mycobacterium strains with altered mycolate profiles are sometimes resistant to the antituberculosis drug Isoniazid.

Ojha, A., et al., "GroEL1: A dedicated chaperone involved in mycolic acid biosynthesis during biofilm formation in mycobacteria" in Cell Volume 123, Issue 5, 2 December 2005, pages 861-873 (DOI: 10.1016/j.cell.2005.09.012)

1 comment:

Shekhar said...

Well, the GroEL of M. tuberculosis are quite enigmatic. We are not quite sure if they function as canonical chaperonins, as they do not attain the proper oligomeric assembly. We had shown a few years ago (Qamra et al., 2004, J Mol Biol, Qamra and mande, 2004, J Bacteriol) that their loss of chaperoning ability is correlated with the loss of their oligomeric form. We have recently confirmed this using hetereologos complementaion in E. coli. As far the KasA story, we think that the final word on its ability to fold/ not fold KasA is yet unclear.