title: Toxin-antitoxin vapBC locus participates in formation of the dormant state in Mycobacterium smegmatis.
abstract: Toxin-antitoxin (TA) loci are widely spread in bacterial plasmids and chromosomes. Toxins affect important functions of bacterial cells such as translation, replication and cell-wall synthesis, whereas antitoxins are toxin inhibitors. Participation in formation of the dormant state in bacteria is suggested to be a possible function of toxins. Here we show that overexpression of VapC toxin in Mycobacterium smegmatis results in development of morphologically distinct ovoid cells. The ovoid cells were nonreplicating and revealed a low level of uracil incorporation and respiration that indicated their dormant status. To validate the role of VapBC in dormancy formation, we used a model of dormant, 'nonculturable' (NC) M. smegmatis cells obtained in potassium-limited conditions. Overexpression of VapB antitoxin prevented transition to dormancy, presumably due to a decreased level of the free VapC protein. Indeed, this effect of the VapB was neutralized by coexpression of the cognate VapC as a part of the vapBC operon. In summary, these findings reveal participation of vapBC products in formation of the dormant state in M. smegmatis.
authors.affiliation: Laboratory of Biochemistry of Stresses in Microorganisms, A.N. Bach Institute of Biochemistry Russian Academy of Sciences, Moscow, Russia.
authors.forename: Oksana I
authors.initials: OI
authors.lastname: Demidenok
authors.forename: Arseny S
authors.initials: AS
authors.lastname: Kaprelyants
authors.forename: Anna V
authors.initials: AV
authors.lastname: Goncharenko
mesh_terms: D000992:Antitoxins / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*
chemical_list: D000992:Antitoxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; C000592554:VapC protein, Mycobacterium smegmatis; C077517:VapB protein, Bacteria
keywords: TA modules; dormant mycobacteria; nonculturability