MtrA response regulator controls cell division and cell wall metabolism and affects susceptibility of mycobacteria to the first line antituberculosis drugs

Purushotham Gorla, Renata Plocinska, Krishna Sarva, Akash T. Satsangi, Emmanuel Pandeeti, Robert Donnelly, Jaroslaw Dziadek, Malini Rajagopalan, Murty V. Madiraju

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The biological processes regulated by the essential response regulator MtrA and the growth conditions promoting its activation in Mycobacterium tuberculosis, a slow grower and pathogen, are largely unknown. Here, using a gain-of-function mutant, MtrAY102C, which functions in the absence of the cognate MtrB sensor kinase, we show that the MtrA regulon includes several genes involved in the processes of cell division and cell wall metabolism. The expression of selected MtrA targets and intracellular MtrA levels were compromised under replication arrest induced by genetic manipulation and under stress conditions caused by toxic radicals. The loss of the mtrA gene in M. smegmatis, a rapid grower and non-pathogen, produced filamentous cells with branches and bulges, indicating defects in cell division and cell shape. The ΔmtrA mutant was sensitized to rifampicin and vancomycin and became more resistant to isoniazid, the first line antituberculosis drug. Our data are consistent with the proposal that MtrA controls the optimal cell division, cell wall integrity, and susceptibility to some antimycobacterial drugs.

Original languageEnglish (US)
Article number2839
JournalFrontiers in Microbiology
Volume9
Issue numberNOV
DOIs
StatePublished - Nov 23 2018

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Microbiology (medical)

Keywords

  • MtrA-CHIPSeq
  • MtrA-cell division
  • MtrA-response regulator
  • Mycobacterium
  • Two component regulatory system

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