The T2R38 bitter taste receptor as a modifier of host response to Pseudomonas aeruginosa in cystic fibrosis: does T2R38 genotype impact on clinical infection?
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Accepted version
Author(s)
Type
Journal Article
Abstract
Pseudomonas aeruginosa (Pa) utilises quorum sensing
(QS) to mediate several virulence factors including growth in biofilms.
Intriguing in vitro data suggests QS signalling molecules can be “sensed” at
the epithelial surface via the T2R38 (bitter taste) receptor expressed on air-
way cilia (Lee RJ, et al. J Clin Invest. 2012;122:4145-59). Activation of this
receptor is predicted to lead to changes in ciliary beat frequency and nitric
oxide production, which may enhance bacterial clearance. Three common
polymorphisms exist in the gene coding for this receptor, altering the amino
acid sequence at positions 49, 262, and 296 and correlating with receptor
function; the functional allele has proline-alanine-valine (PAV) whereas the
non-functional allele has alanine-valine-isoleucine (AVI) at these residues.
In vitro response to QS molecules has been shown to be greatest in cells
with the PAV/PAV genotype. We hypothesised that the T2R38 receptor
may be important in host defence against Pa in people with cystic fibrosis
(CF) and that T2R38 genotype may therefore modify infection status and
clinical outcomes.
(QS) to mediate several virulence factors including growth in biofilms.
Intriguing in vitro data suggests QS signalling molecules can be “sensed” at
the epithelial surface via the T2R38 (bitter taste) receptor expressed on air-
way cilia (Lee RJ, et al. J Clin Invest. 2012;122:4145-59). Activation of this
receptor is predicted to lead to changes in ciliary beat frequency and nitric
oxide production, which may enhance bacterial clearance. Three common
polymorphisms exist in the gene coding for this receptor, altering the amino
acid sequence at positions 49, 262, and 296 and correlating with receptor
function; the functional allele has proline-alanine-valine (PAV) whereas the
non-functional allele has alanine-valine-isoleucine (AVI) at these residues.
In vitro response to QS molecules has been shown to be greatest in cells
with the PAV/PAV genotype. We hypothesised that the T2R38 receptor
may be important in host defence against Pa in people with cystic fibrosis
(CF) and that T2R38 genotype may therefore modify infection status and
clinical outcomes.
Date Issued
2016-09-21
Date Acceptance
2016-09-01
Citation
Pediatric Pulmonology, 2016, 51 (S45), pp.323-323
ISSN
8755-6863
Publisher
Wiley
Start Page
323
End Page
323
Journal / Book Title
Pediatric Pulmonology
Volume
51
Issue
S45
Copyright Statement
© 2016 Wiley Periodicals, Inc. This is the accepted version of the following article: 2016, Poster Session Abstracts. Pediatr Pulmonol., 51: S194–S485. doi:10.1002/ppul.23576, which has been published in final form at https://dx.doi.org/10.1002/ppul.23576
Sponsor
Cystic Fibrosis Trust
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000384815300420&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
SRC 001
Subjects
Science & Technology
Life Sciences & Biomedicine
Pediatrics
Respiratory System
1114 Paediatrics And Reproductive Medicine
Publication Status
Published