Interaction of the sensor module of Mycobacterium tuberculosis H37Rv KdpD with members of the Lpr family.

Abstract:

:The genetic and biochemical mechanisms by which Mycobacterium tuberculosis senses and responds to the complex environment that it encounters during infection and persistence within the host remain unknown. In a number of bacterial species, the Kdp signal transduction pathway appears to be the primary response to environmental osmotic stress, which is primarily mediated by K+ concentration in bacteria. We show that kdp encodes for components of a mycobacterial signalling pathway by demonstrating the K+ dependence of kdpFABC expression in both M. tuberculosis H37Rv and Mycobacterium smegmatis. To identify proteins of M. tuberculosis that participate in this signalling pathway, we used the N-terminal sensing module of the histidine kinase KdpD as bait in a yeast two-hybrid screen. We show that the sensing domain of KdpD interacts specifically with two membrane lipoproteins, LprJ (Rv1690) and LprF (Rv1368). Overexpression of lprF and lprJ alleles in mycobacterial kdpF-lacZ reporter strains enabled us to identify alleles that modulate kdpFABC expression. By exploiting the yeast three-hybrid system, we have found that the histidine kinase domain of KdpD forms ternary complexes with LprF and LprJ and the sensing module of KdpD. Our results establish a role for membrane proteins in the Kdp signalling pathway and suggest that LprF and LprJ function as accessory or ligand-binding proteins that communicate directly with the sensing domain of KdpD to modulate kdp expression.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Steyn AJ,Joseph J,Bloom BR

doi

10.1046/j.1365-2958.2003.03356.x

subject

Has Abstract

pub_date

2003-02-01 00:00:00

pages

1075-89

issue

4

eissn

0950-382X

issn

1365-2958

pii

3356

journal_volume

47

pub_type

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