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Front. Microbiol. | doi: 10.3389/fmicb.2018.02839

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

 Purushotham Gorla1,  Renata Plocinska2*, Krishna Sarva1,  Akash T. Satsangi1, Emmanuel Pandeeti1,  Robert Donelly3,  Jarosław Dziadek2, Malini Rajagopalan1* and  Murty V. Madiraju1
  • 1University of Texas at Tyler, United States
  • 2Institute for Medical Biology (PAN), Poland
  • 3Medical School, Rutgers, The State University of New Jersey, United States

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.

Keywords: Mycobacterium, Two component regulatory system, MtrA-CHIPSeq, MtrA-cell division, MtrA-response regulator

Received: 13 Sep 2018; Accepted: 05 Nov 2018.

Edited by:

Marie-Joelle VIROLLE, Centre national de la recherche scientifique (CNRS), France

Reviewed by:

Xiuhua Pang, Shandong University, China
Jean-François CAVALIER, UMR7255 Laboratoire d'ingénierie des systèmes macromoléculaires (LISM), France  

Copyright: © 2018 Gorla, Plocinska, Sarva, Satsangi, Pandeeti, Donelly, Dziadek, Rajagopalan and Madiraju. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Renata Plocinska, Institute for Medical Biology (PAN), Łódź, Poland, rplocinska@cbm.pan.pl
Prof. Malini Rajagopalan, University of Texas at Tyler, Tyler, 75799, Texas, United States, malinir1@gmail.com