title: Mycobacterium tuberculosis MtrB sensor kinase interactions with FtsI and Wag31 proteins reveal a role for MtrB distinct from that regulating MtrA activities.
abstract: The septal association of Mycobacterium tuberculosis MtrB, the kinase partner of the MtrAB two-component signal transduction system, is necessary for the optimal expression of the MtrA regulon targets, including ripA, fbpB, and ftsI, which are involved in cell division and cell wall synthesis. Here, we show that MtrB, irrespective of its phosphorylation status, interacts with Wag31, whereas only phosphorylation-competent MtrB interacts with FtsI. We provide evidence that FtsI depletion compromises the MtrB septal assembly and MtrA regulon expression; likewise, the absence of MtrB compromises FtsI localization and, possibly, FtsI activity. We conclude from these results that FtsI and MtrB are codependent for their activities and that FtsI functions as a positive modulator of MtrB activation and MtrA regulon expression. In contrast to FtsI, Wag31 depletion does not affect MtrB septal assembly and MtrA regulon expression, whereas the loss of MtrB increased Wag31 localization and the levels of PknA/PknB (PknA/B) serine-threonine protein kinase-mediated Wag31 phosphorylation. Interestingly, we found that FtsI decreased levels of phosphorylated Wag31 (Wag31∼P) and that MtrB interacted with PknA/B. Overall, our results indicate that MtrB interactions with FtsI, Wag31, and PknA/B are required for its optimal localization, MtrA regulon expression, and phosphorylation of Wag31. Our results emphasize a new role for MtrB in cell division and cell wall synthesis distinct from that regulating the MtrA phosphorylation activities.
authors.affiliation: The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: Renata
authors.initials: R
authors.lastname: Plocinska
authors.affiliation: The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Martinez
authors.affiliation: The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: Purushotham
authors.initials: P
authors.lastname: Gorla
authors.affiliation: The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pandeeti
authors.affiliation: The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Sarva
authors.affiliation: The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Blaszczyk
authors.affiliation: Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Dziadek
authors.affiliation: The University of Texas Health Science Center at Tyler, Tyler, Texas, USA Murty.madiraju@uthct.edu Malini.rajagopalan@uthct.edu.
authors.forename: Murty V
authors.initials: MV
authors.lastname: Madiraju
authors.affiliation: The University of Texas Health Science Center at Tyler, Tyler, Texas, USA Murty.madiraju@uthct.edu Malini.rajagopalan@uthct.edu.
authors.forename: Malini
authors.initials: M
authors.lastname: Rajagopalan
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000378:metabolism*; D046928:Peptidoglycan Glycosyltransferase / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; C100938:MtrA protein, Bacteria; C079092:MtrB protein, Bacteria; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C000591547:Wag31 protein, Mycobacterium tuberculosis; D046928:Peptidoglycan Glycosyltransferase