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The whooping cough agent Bordetella pertussis coordinately regulates the expression of its virulence factors with the two-component system BvgAS. In laboratory conditions, specific chemical modulators are used to trigger phenotypic modulation of B. pertussis from its default virulent Bvg+ phase to avirulent Bvg- or intermediate Bvgi phases, in which no virulence factors or only a subset of them are produced, respectively. Whether phenotypic modulation occurs in the host remains unknown. In this work, recombinant B. pertussis strains harboring BvgS variants were tested in a mouse model of infection and analyzed using transcriptomic approaches. Recombinant BP-BvgΔ65, which is in the Bvgi phase by default and can be up-modulated to the Bvg+ phase in vitro, could colonize the mouse nose but was rapidly cleared from the lungs, while Bvg+-phase strains colonized both organs for up to four weeks. These results indicated that phenotypic modulation, which might have restored the full virulence capability of BP-BvgΔ65, does not occur in mice or is temporally or spatially restricted and has no effect in those conditions. Transcriptomic analyses of this and other recombinant Bvgi and Bvg+-phase strains revealed that two distinct ranges of virulence gene expression allow colonization of the mouse nose and lungs, respectively. We also showed that a recombinant strain expressing moderately lower levels of the virulence genes than its wild type parent was as efficient at colonizing both organs. Altogether, genetic modifications of BvgS generate a range of phenotypic phases, which are useful tools to decipher host-pathogen interactions.

Competing Interests: The authors have declared that no competing interests exist.

Titel:	Distinct virulence ranges for infection of mice by Bordetella pertussis revealed by engineering of the sensor-kinase BvgS.
Autor/in / Beteiligte Person:	Lesne, E ; Coutte, L ; Solans, L ; Slupek, S ; Debrie, AS ; Dhennin, V ; Froguel, P ; Hot, D ; Locht, C ; Antoine, R ; Jacob-Dubuisson, F
Link:	Volltext (PDF)
Zeitschrift:	PloS one, Jg. 13 (2018-10-11), Heft 10, S. e0204861
Veröffentlichung:	San Francisco, CA : Public Library of Science, 2018
Medientyp:	academicJournal
ISSN:	1932-6203 (electronic)
DOI:	10.1371/journal.pone.0204861
Schlagwort:	Animals Bacterial Proteins metabolism Bordetella pertussis genetics Disease Models, Animal Gene Expression Profiling Gene Expression Regulation, Bacterial Host-Pathogen Interactions Lung microbiology Mice Nose microbiology Protein Engineering Sequence Analysis, RNA Transcription Factors metabolism Bacterial Proteins genetics Bordetella pertussis pathogenicity Mutation Transcription Factors genetics Virulence Whooping Cough microbiology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [PLoS One] 2018 Oct 11; Vol. 13 (10), pp. e0204861. <i>Date of Electronic Publication: </i>2018 Oct 11 (<i>Print Publication: </i>2018). MeSH Terms: Mutation* ; Virulence* ; Bacterial Proteins / genetics ; Bordetella pertussis / pathogenicity ; Transcription Factors / genetics ; Whooping Cough / microbiology ; Animals ; Bacterial Proteins / metabolism ; Bordetella pertussis / genetics ; Disease Models, Animal ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Host-Pathogen Interactions ; Lung / microbiology ; Mice ; Nose / microbiology ; Protein Engineering ; Sequence Analysis, RNA ; Transcription Factors / metabolism References: Mol Microbiol. 1996 Apr;20(1):17-25. (PMID: 8861200) ; Sci Rep. 2016 Sep 13;6:32774. (PMID: 27620673) ; J Biol Chem. 2015 Sep 18;290(38):23307-19. (PMID: 26203186) ; J Biol Chem. 1993 May 25;268(15):11348-55. (PMID: 8496186) ; PLoS Biol. 2017 Apr 12;15(4):e2000420. (PMID: 28403138) ; AAPS PharmSci. 1999;1(2):E2. (PMID: 11741199) ; Infect Immun. 2012 Mar;80(3):1025-36. (PMID: 22158743) ; J Infect Dis. 2018 May 25;217(12):1987-1996. (PMID: 29528444) ; Curr Opin Microbiol. 2001 Feb;4(1):82-9. (PMID: 11173039) ; PLoS One. 2012;7(2):e31985. (PMID: 22348138) ; Mol Microbiol. 2001 May;40(3):669-83. (PMID: 11359572) ; J Bacteriol. 1992 Feb;174(3):970-9. (PMID: 1732230) ; Vaccines (Basel). 2015 Sep 14;3(3):751-70. (PMID: 26389958) ; PLoS One. 2009 Sep 14;4(9):e6996. (PMID: 19750014) ; Nucleic Acids Res. 2013 Aug;41(14):e140. (PMID: 23716638) ; Mol Microbiol. 1997 May;24(4):671-85. (PMID: 9194696) ; J Biol Chem. 2017 May 12;292(19):8048-8058. (PMID: 28348085) ; Mol Microbiol. 2005 Nov;58(3):700-13. (PMID: 16238621) ; MBio. 2017 Oct 10;8(5):. (PMID: 29018122) ; MBio. 2016 Mar 01;7(2):e02089. (PMID: 26933056) ; Clin Vaccine Immunol. 2014 Feb;21(2):119-25. (PMID: 24256623) ; EMBO J. 1991 Dec;10(12):3971-5. (PMID: 1718746) ; J Infect. 2017 Jun;74 Suppl 1:S114-S119. (PMID: 28646950) ; J Bacteriol. 2006 Mar;188(5):1775-85. (PMID: 16484188) ; MBio. 2018 Feb 27;9(1):. (PMID: 29487240) ; Emerg Infect Dis. 2014 Apr;20(4):626-33. (PMID: 24655754) ; J Proteomics. 2016 Mar 16;136:55-67. (PMID: 26873878) ; Clin Infect Dis. 2015 Jan 15;60(2):223-7. (PMID: 25301209) ; Microbiol Rev. 1993 Jun;57(2):320-46. (PMID: 8336670) ; Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):E1519-E1527. (PMID: 28167784) ; Mol Microbiol. 2005 Feb;55(3):788-98. (PMID: 15661004) ; PLoS One. 2014 Jan 08;9(1):e83449. (PMID: 24421886) ; J Bacteriol. 2017 Aug 22;199(18):. (PMID: 28507245) ; J Biol Chem. 1996 Dec 27;271(52):33176-80. (PMID: 8969172) ; Gene. 1994 Dec 2;150(1):123-7. (PMID: 7959037) ; PLoS Pathog. 2015 Mar 04;11(3):e1004700. (PMID: 25738876) ; Infect Immun. 1998 Jun;66(6):2762-8. (PMID: 9596745) ; Infect Immun. 2006 Oct;74(10):5537-48. (PMID: 16988229) ; J Infect Dis. 2017 Jul 1;216(1):117-124. (PMID: 28535276) ; Infect Immun. 2005 Feb;73(2):748-60. (PMID: 15664913) ; Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17351-5. (PMID: 20855615) ; Genetika. 2016 Apr;52(4):422-30. (PMID: 27529975) ; PLoS One. 2014 Jan 08;9(1):e84523. (PMID: 24416242) ; J Bacteriol. 2002 Dec;184(24):6942-51. (PMID: 12446644) Substance Nomenclature: 0 (Bacterial Proteins) ; 0 (Transcription Factors) ; 0 (bvgS protein, Bordetella pertussis) Entry Date(s): Date Created: 20181012 Date Completed: 20190322 Latest Revision: 20190322 Update Code: 20240513 PubMed Central ID: PMC6181320

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Distinct virulence ranges for infection of mice by Bordetella pertussis revealed by engineering of the sensor-kinase BvgS.