title: MazF6 toxin of Mycobacterium tuberculosis demonstrates antitoxin specificity and is coupled to regulation of cell growth by a Soj-like protein.
abstract: BACKGROUND
  Molecular programs employed by Mycobacterium tuberculosis (Mtb) for the establishment of non-replicating persistence (NRP) are poorly understood. In order to investigate mechanisms regulating entry into NRP, we asked how cell cycle regulation is linked to downstream adaptations that ultimately result in NRP. Based on previous reports and our recent studies, we reason that, in order to establish NRP, cells are halted in the cell cycle at the point of septum formation by coupled regulatory mechanisms.
  
  
  RESULTS
  Using bioinformatic consensus modeling, we identified an alternative cell cycle regulatory element, Soj(Mtb) encoded by rv1708. Soj(Mtb) coordinates a regulatory mechanism involving cell cycle control at the point of septum formation and elicits the induction of the MazF6 toxin. MazF6 functions as an mRNA interferase leading to bacteriostasis that can be prevented by interaction with its cognate antitoxin, MazE6. Further, MazEF6 acts independently of other Maz family toxin:antitoxin pairs. Notably, soj(Mtb) and mazEF6 transcripts where identified at 20, 40 and 100 days post-infection in increasing abundance indicating a role in adaption during chronic infection.
  
  
  CONCLUSIONS
  Here we present the first evidence of a coupled regulatory system in which cell cycle regulation via Soj(Mtb) is linked to downstream adaptations that are facilitated through the activity of the MazEF6 TA pair.
authors.forename: Melissa V
authors.initials: MV
authors.lastname: Ramirez
authors.forename: Clinton C
authors.initials: CC
authors.lastname: Dawson
authors.forename: Rebecca
authors.initials: R
authors.lastname: Crew
authors.forename: Kathleen
authors.initials: K
authors.lastname: England
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA. richard.slayden@colostate.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Slayden
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000254:growth & development* / Q000648:ultrastructure; D016415:Sequence Alignment
chemical_list: D001427:Bacterial Toxins