Mycobacterium tuberculosis Cpn60.2 and DnaK are Located on the Bacterial Surface, where Cpn60.2 Facilitates Efficient Bacterial Association with Macrophages. - Related Articles
Mycobacterium tuberculosis Cpn60.2 and DnaK are Located on the Bacterial Surface, where Cpn60.2 Facilitates Efficient Bacterial Association with Macrophages.
Infect Immun. 2009 May 26;
Authors: Hickey TB, Thorson LM, Speert DP, Daffé M, Stokes RW
Mycobacterium tuberculosis, the causative agent of Tuberculosis, initially contacts host cells with elements of its outer cell wall, or capsule. We have shown that capsular material from the surface of M. tuberculosis competitively inhibits the non-opsonic binding of whole M. tuberculosis bacilli to macrophages in a dose-dependent manner that is not acting through a global inhibition of macrophage binding. We have further demonstrated that isolated M. tuberculosis capsular proteins mediate a major part of this inhibition. 2D-PAGE analysis of the capsular proteins showed the presence of a wide variety of protein species, including proportionately high levels of the Cpn60.2 (Hsp65, GroEL2) and DnaK (Hsp70) molecular chaperones. Both of these proteins were subsequently detected on the bacterial surface. To determine whether these molecular chaperones play a role in bacterial binding, recombinant Cpn60.2 and DnaK were tested for their ability to inhibit the association of M. tuberculosis bacilli with macrophages. We found that recombinant Cpn60.2 can inhibit approximately 57% of bacterial association with macrophages while DnaK was not inhibitory at comparable concentrations. Additionally, when polyclonal F(ab')2 fragments of anti-Cpn60.2 and anti-DnaK were used to mask the surface presentation of these molecular chaperones, a binding reduction of approximately 34% was seen for anti-Cpn60.2 (F(ab')2), while anti-DnaK(F(ab')2) did not significantly reduce bacterial association with macrophages. Thus, our findings suggest that while M. tuberculosis displays both surface-associated Cpn60.2 and DnaK, only Cpn60.2 demonstrates adhesin functionality with regards to macrophage interaction.
PMID: 19470749 [PubMed - as supplied by publisher] [Tuberculosis Pulmonary]