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Gene regulation network in Pseudomonas aeruginosa is complex. With a relatively large genome (6.2 Mb), there is a significant portion of genes that are proven or predicted to be transcriptional regulators. Many of these regulators have been shown to play important roles in biofilm formation and maintenance. In this study, we present a novel transcriptional regulator, PA1226, which modulates biofilm formation and virulence in P. aeruginosa. Mutation in the gene encoding this regulator abolished the ability of P. aeruginosa to produce biofilms in vitro, without any effect on the planktonic growth. This regulator is also essential for the in vivo fitness and pathogenesis in both Drosophila melanogaster and BALB/c mouse lung infection models. Transcriptome analysis revealed that PA1226 regulates many essential virulence genes/pathways, including those involved in alginate, pili, and LPS biosynthesis. Genes/operons directly regulated by PA1226 and potential binding sequences were identified via ChIP-seq. Attempts to confirm the binding sequences by electrophoretic mobility shift assay led to the discovery of a co-regulator, PA1413, via co-immunoprecipitation assay. PA1226 and PA1413 were shown to bind collaboratively to the promoter regions of their regulons. A model is proposed, summarizing our finding on this novel dual-regulation system.

Titel:	Novel dual regulators of Pseudomonas aeruginosa essential for productive biofilms and virulence.
Autor/in / Beteiligte Person:	Heacock-Kang, Y ; Zarzycki-Siek, J ; Sun, Z ; Poonsuk, K ; Bluhm, AP ; Cabanas, D ; Fogen, D ; McMillan, IA ; Chuanchuen, R ; Hoang, TT
Zeitschrift:	Molecular microbiology, Jg. 109 (2018-08-01), Heft 3, S. 401-414
Veröffentlichung:	Oxford, OX ; Boston, MA : Blackwell Scientific Publications, c1987-, 2018
Medientyp:	academicJournal
ISSN:	1365-2958 (electronic)
DOI:	10.1111/mmi.14063
Schlagwort:	Animals Bacterial Proteins genetics Bacterial Proteins metabolism Disease Models, Animal Drosophila melanogaster Gene Expression Profiling Humans Lung Diseases microbiology Male Mice Mice, Inbred BALB C Pseudomonas aeruginosa genetics Transcription Factors genetics Virulence Biofilms growth & development Pseudomonas Infections microbiology Pseudomonas aeruginosa pathogenicity Pseudomonas aeruginosa physiology Transcription Factors metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural Language: English [Mol Microbiol] 2018 Aug; Vol. 109 (3), pp. 401-414. <i>Date of Electronic Publication: </i>2018 Jul 31. MeSH Terms: Biofilms / growth & development ; Pseudomonas Infections / microbiology ; Pseudomonas aeruginosa / pathogenicity ; Pseudomonas aeruginosa / physiology ; Transcription Factors / *metabolism ; Animals ; Bacterial Proteins / genetics ; Bacterial Proteins / metabolism ; Disease Models, Animal ; Drosophila melanogaster ; Gene Expression Profiling ; Humans ; Lung Diseases / microbiology ; Male ; Mice ; Mice, Inbred BALB C ; Pseudomonas aeruginosa / genetics ; Transcription Factors / genetics ; Virulence References: Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1490-4. (PMID: 7878006) ; Nucleic Acids Res. 2002 Jan 1;30(1):207-10. (PMID: 11752295) ; Mol Microbiol. 2017 Dec;106(6):976-985. (PMID: 29030956) ; Microbiology (Reading). 2008 Jun;154(Pt 6):1584-1598. (PMID: 18524913) ; Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14339-44. (PMID: 14617778) ; Nat Protoc. 2006;1(1):153-61. (PMID: 17406227) ; Nature. 2000 Oct 12;407(6805):762-4. (PMID: 11048725) ; Science. 1993 May 21;260(5111):1127-30. (PMID: 8493556) ; Trends Microbiol. 2001 Jan;9(1):34-9. (PMID: 11166241) ; Methods Mol Biol. 2010;627:91-100. (PMID: 20217615) ; FEMS Microbiol Rev. 2012 Jul;36(4):893-916. (PMID: 22212072) ; Environ Microbiol. 2012 Aug;14(8):1995-2005. (PMID: 22513190) ; J Biol Chem. 2015 May 15;290(20):12451-62. (PMID: 25817996) ; J Bacteriol. 2005 Feb;187(3):1192-5. (PMID: 15659695) ; mBio. 2015 May 12;6(3):e00453-15. (PMID: 25968647) ; Int J Med Microbiol. 2006 Apr;296(2-3):73-81. (PMID: 16476569) ; Chest. 1999 Mar;115(3 Suppl):28S-33S. (PMID: 10084457) ; Environ Microbiol. 2014 Jul;16(7):1961-81. (PMID: 24592823) ; Front Cell Infect Microbiol. 2014 Jun 20;4:82. (PMID: 24999454) ; Science. 1995 Jun 30;268(5219):1899-902. (PMID: 7604262) ; Appl Environ Microbiol. 2001 Apr;67(4):1865-73. (PMID: 11282644) ; Nat Protoc. 2015 Jul;10(7):974-84. (PMID: 26042386) ; Mol Microbiol. 2008 Jul;69(2):376-89. (PMID: 18485075) ; PLoS Pathog. 2011 Oct;7(10):e1002299. (PMID: 21998591) ; Microbiol Mol Biol Rev. 2012 Mar;76(1):46-65. (PMID: 22390972) ; Microbiology (Reading). 1994 Jul;140 ( Pt 7):1745-54. (PMID: 7521247) ; Gene. 1994 Oct 11;148(1):81-6. (PMID: 7926843) ; Science. 1998 Apr 10;280(5361):295-8. (PMID: 9535661) ; Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17981-6. (PMID: 24143808) ; J Bacteriol. 1997 Sep;179(18):5756-67. (PMID: 9294432) ; Monaldi Arch Chest Dis. 1997 Aug;52(4):363-6. (PMID: 9401367) ; J Dairy Sci. 1998 Oct;81(10):2760-4. (PMID: 9812281) ; Science. 2002 Feb 22;295(5559):1487. (PMID: 11859186) ; Gene. 1997 Jun 19;192(2):271-81. (PMID: 9224900) ; Br Med Bull. 1992 Oct;48(4):912-30. (PMID: 1281036) ; Mol Microbiol. 2009 Jul;73(1):120-36. (PMID: 19508282) ; Trends Microbiol. 2014 Jun;22(6):326-33. (PMID: 24598086) ; J Biomol Tech. 2006 Apr;17(2):103-13. (PMID: 16741237) ; PLoS Pathog. 2009 Mar;5(3):e1000354. (PMID: 19325879) ; FEBS Lett. 2006 Jul 10;580(16):3883-8. (PMID: 16797016) ; Bioinformatics. 2011 Mar 1;27(5):715-7. (PMID: 21183585) ; Infect Immun. 2005 Apr;73(4):2504-14. (PMID: 15784597) ; Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):197-201. (PMID: 8278364) ; ACS Chem Biol. 2017 Apr 21;12(4):1056-1065. (PMID: 28192658) ; J Bacteriol. 1996 Jan;178(1):46-53. (PMID: 8550441) ; Genome Res. 2011 Jun;21(6):925-35. (PMID: 21536723) ; Curr Opin Infect Dis. 2000 Aug;13(4):377-384. (PMID: 11964806) ; J Bacteriol. 2008 Mar;190(6):2023-30. (PMID: 18178737) ; Nat Rev Drug Discov. 2003 Feb;2(2):114-22. (PMID: 12563302) ; Crit Care Med. 1999 May;27(5):887-92. (PMID: 10362409) ; Infect Immun. 2007 Nov;75(11):5313-24. (PMID: 17724070) ; Mol Microbiol. 1996 Nov;22(3):481-95. (PMID: 8939432) ; Ochsner J. 2009 Spring;9(1):27-31. (PMID: 21603406) ; Nature. 2001 Oct 25;413(6858):860-4. (PMID: 11677611) ; Ann R Coll Surg Engl. 2010 Sep;92(6):453-8. (PMID: 20819330) ; Cold Spring Harb Protoc. 2009 Mar;2009(3):pdb.prot5168. (PMID: 20147103) Grant Information: R21 AI123913 United States AI NIAID NIH HHS; R01 GM103580 United States GM NIGMS NIH HHS Substance Nomenclature: 0 (Bacterial Proteins) ; 0 (Transcription Factors) Entry Date(s): Date Created: 20180712 Date Completed: 20190705 Latest Revision: 20240331 Update Code: 20240331 PubMed Central ID: PMC6158065

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Novel dual regulators of Pseudomonas aeruginosa essential for productive biofilms and virulence.