title: ChiZ levels modulate cell division process in mycobacteria.
abstract: We have previously shown that expression of chiZ (Rv2719c), encoding a cell wall hydrolase, is upregulated in response to DNA damaging agents and exposure to cephalexin. Furthermore, increased levels of ChiZ lead to decreased viability, loss of membrane integrity and defects in FtsZ-GFP localization and cell division. We now show that ChiZ N'-terminal 110 amino acid region, containing the cell wall hydrolase activity, is sufficient to modulate FtsZ-GFP localization. Further, we found that FtsZ-GFP rings are stabilized in a chiZ deletion strain indicating that ChiZ activity regulates FtsZ assembly. Overexpression of ftsZ did not reverse the reduction in viability caused by overproduction of ChiZ indicating that ChiZ neither interacts with nor directly influences FtsZ assembly. Bacterial two-hybrid assays revealed that ChiZ interacts with FtsI and FtsQ, two other septasomal proteins, but not with FtsZ. Finally, we show that ChiZ is not required for virulence of Mycobacterium tuberculosis in murine macrophages and mice. Our data suggest that optimal levels and activity of the cell wall hydrolase ChiZ are required for regulated cell division in mycobacteria.
authors.affiliation: Biomedical Research, The University of Texas Health Science Center, Tyler, TX, USA.
authors.forename: Indumathi S
authors.initials: IS
authors.lastname: Vadrevu
authors.forename: Hava
authors.initials: H
authors.lastname: Lofton
authors.forename: Krishna
authors.initials: K
authors.lastname: Sarva
authors.forename: Ewelina
authors.initials: E
authors.lastname: Blasczyk
authors.forename: Renata
authors.initials: R
authors.lastname: Plocinska
authors.forename: Jagannath
authors.initials: J
authors.lastname: Chinnaswamy
authors.forename: Murty
authors.initials: M
authors.lastname: Madiraju
authors.forename: Malini
authors.initials: M
authors.lastname: Rajagopalan
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006867:Hydrolases / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009164:Mycobacterium Infections / Q000378:metabolism* / Q000382:microbiology; D020102:Mycobacterium smegmatis / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000166:cytology* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D020798:Two-Hybrid System Techniques; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; D008565:Membrane Proteins; D006867:Hydrolases
references.citation: Infect Immun. 2006 Feb;74(2):1233-42
references.pmid: 16428773
references.citation: Microbiology (Reading). 2008 Mar;154(Pt 3):725-735
references.pmid: 18310019
references.citation: Microbiology (Reading). 2002 Apr;148(Pt 4):961-971
references.pmid: 11932443
references.citation: PLoS One. 2010 Jan 06;5(1):e8590
references.pmid: 20066037
references.citation: J Bacteriol. 2006 Mar;188(5):1856-65
references.pmid: 16484196
references.citation: PLoS One. 2010 Jul 06;5(7):e11058
references.pmid: 20625433
references.citation: Science. 2010 May 14;328(5980):856-61
references.pmid: 20466923
references.citation: J Exp Med. 2003 Sep 1;198(5):693-704
references.pmid: 12953091
references.citation: Biochem Biophys Res Commun. 2005 Jun 17;331(4):1171-7
references.pmid: 15882999
references.citation: Science. 2009 Feb 27;323(5918):1215-8
references.pmid: 19251630
references.citation: Nat Med. 2010 Apr;16(4):466-9
references.pmid: 20305661
references.citation: Mol Microbiol. 2007 Nov;66(3):658-68
references.pmid: 17919286
references.citation: J Bacteriol. 2008 Jun;190(12):4360-6
references.pmid: 18408028
references.citation: J Biol Chem. 2002 Jul 12;277(28):24983-7
references.pmid: 12101218
references.citation: Mol Microbiol. 2002 Feb;43(3):717-31
references.pmid: 11929527
references.citation: Adv Microb Physiol. 2010;57:43-117
references.pmid: 21078441
references.citation: J Biol Chem. 2002 May 24;277(21):18753-62
references.pmid: 11821396
references.citation: Trends Microbiol. 2011 Jul;19(7):307-14
references.pmid: 21561773
references.citation: FEMS Microbiol Lett. 1998 Oct 15;167(2):151-6
references.pmid: 9809415
references.citation: Mol Microbiol. 2006 May;60(3):643-57
references.pmid: 16629667
references.citation: Biochimie. 2001 Jan;83(1):103-8
references.pmid: 11254982
references.citation: BMC Microbiol. 2011 Apr 19;11:79
references.pmid: 21504606
references.citation: J Bacteriol. 2011 Jul;193(13):3246-56
references.pmid: 21531798
references.citation: Cell Host Microbe. 2007 Nov 15;2(5):352-64
references.pmid: 18005756
references.citation: J Bacteriol. 2007 Nov;189(21):7896-910
references.pmid: 17766411
references.citation: Microbiol Mol Biol Rev. 1998 Mar;62(1):181-203
references.pmid: 9529891
references.citation: J Parasitol. 2003 Oct;89(5):895-8
references.pmid: 14627134
references.citation: Mol Microbiol. 2006 Dec;62(6):1655-73
references.pmid: 17427288
references.citation: J Biol Chem. 2006 Dec 29;281(52):40107-13
references.pmid: 17068335
references.citation: J Bacteriol. 2002 Nov;184(22):6093-9
references.pmid: 12399477
references.citation: Science. 2008 Sep 19;321(5896):1644-5
references.pmid: 18801989
references.citation: Mol Microbiol. 2006 Oct;62(1):132-47
references.pmid: 16942606
references.citation: Nature. 1998 Jun 11;393(6685):537-44
references.pmid: 9634230
references.citation: PLoS Pathog. 2008 Feb 29;4(2):e1000001
references.pmid: 18463693
references.citation: J Bacteriol. 2000 Jul;182(14):4028-34
references.pmid: 10869082
references.citation: J Bacteriol. 2005 Apr;187(7):2233-43
references.pmid: 15774864