Imperial College London
Professor Philippe Froguel

ProfessorPhilippeFroguel

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Genomic Medicine
 
 
 
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Contact

 

+44 (0)20 7594 6520p.froguel

 
 
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Assistant

 

Mrs Patricia Murphy +44 (0)20 7594 1603

 
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Location

 

E306Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lesne:2018:10.1371/journal.pone.0204861,
author = {Lesne, E and Coutte, L and Solans, L and Slupek, S and Debrie, A-S and Dhennin, V and Froguel, P and Hot, D and Locht, C and Antoine, R and Jacob-Dubuisson, F},
doi = {10.1371/journal.pone.0204861},
journal = {PLoS ONE},
title = {Distinct virulence ranges for infection of mice by Bordetella pertussis revealed by engineering of the sensor-kinase BvgS},
url = {http://dx.doi.org/10.1371/journal.pone.0204861},
volume = {13},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Lesne,E
AU  - Coutte,L
AU  - Solans,L
AU  - Slupek,S
AU  - Debrie,A-S
AU  - Dhennin,V
AU  - Froguel,P
AU  - Hot,D
AU  - Locht,C
AU  - Antoine,R
AU  - Jacob-Dubuisson,F
DO  - 10.1371/journal.pone.0204861
PY  - 2018///
SN  - 1932-6203
TI  - Distinct virulence ranges for infection of mice by Bordetella pertussis revealed by engineering of the sensor-kinase BvgS
T2  - PLoS ONE
UR  - http://dx.doi.org/10.1371/journal.pone.0204861
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000447173500030&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/64834
VL  - 13
ER  -
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