A lipoprotein modulates activity of the MtrAB two-component system to provide intrinsic multidrug resistance, cytokinetic control and cell wall homeostasis in Mycobacterium

Mol Microbiol. 2010 Apr;76(2):348-64. doi: 10.1111/j.1365-2958.2010.07110.x. Epub 2010 Mar 10.


The MtrAB signal transduction system, which participates in multiple cellular processes related to growth and cell wall homeostasis, is the only two-component system known to be essential in Mycobacterium. In a screen for antibiotic resistance determinants in Mycobacterium smegmatis, we identified a multidrug-sensitive mutant with a transposon insertion in lpqB, the gene located immediately downstream of mtrA-mtrB. The lpqB mutant exhibited increased cell-cell aggregation and severe defects in surface motility and biofilm growth. lpqB cells displayed hyphal growth and polyploidism, reminiscent of the morphology of Streptomyces, a related group of filamentous Actinobacteria. Heterologous expression of M. tuberculosis LpqB restored wild-type characteristics to the lpqB mutant. LpqB interacts with the extracellular domain of MtrB, and influences MtrA phosphorylation and promoter activity of dnaA, an MtrA-regulated gene that affects cell division. Furthermore, in trans expression of the non-phosphorylated, inactive form of MtrA in wild-type M. smegmatis resulted in phenotypes similar to those of lpqB deletion, whereas expression of the constitutively active form of MtrA restored wild-type characteristics to the lpqB mutant. These results support a model in which LpqB, MtrB and MtrA form a three-component system that co-ordinates cytokinetic and cell wall homeostatic processes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Bacterial Proteins / metabolism*
  • Cell Wall / metabolism
  • Cytokinesis*
  • DNA Transposable Elements
  • Drug Resistance, Multiple, Bacterial*
  • Gene Expression Regulation, Bacterial*
  • Genetic Complementation Test
  • Homeostasis
  • Lipoproteins / metabolism*
  • Models, Biological
  • Mutagenesis, Insertional
  • Mycobacterium smegmatis / growth & development
  • Mycobacterium smegmatis / metabolism
  • Mycobacterium smegmatis / physiology*
  • Mycobacterium tuberculosis / genetics
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction
  • Transcription Factors / metabolism*


  • ATP-Binding Cassette Transporters
  • Bacterial Proteins
  • DNA Transposable Elements
  • Lipoproteins
  • MtrA protein, Bacteria
  • MtrB protein, Bacteria
  • RNA-Binding Proteins
  • Transcription Factors