Turnbull, Andrew R, Murphy, Ronan, Behrends, Volker, Lund-Palau, Helena, Simbo, Ameze, Mariveles, Myril, Alton, Eric WFW, Bush, Andrew, Shoemark, Amelia and Davies, Jane C (2018) Impact of T2R38 receptor polymorphisms on Pseudomonas aeruginosa infection in cystic fibrosis. American Journal of Respiratory and Critical Care Medicine, 197 (12). pp. 1635-1638. ISSN 1073-449X

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Abstract

The T2R38 (taste receptor 2 member 38) bitter taste receptor on respiratory epithelia detects Pseudomonas aeruginosa N-acyl-l-homoserine lactones (AHLs). In vitro, T2R38 activation by AHLs initiates calcium-mediated increases in nitric oxide production and ciliary beat frequency, dependent on polymorphisms in the TAS2R38 gene (1). In patients with chronic rhinosinusitis, the TAS2R38 genotype is proposed to modify mucosal responses to P. aeruginosa (1).

Polymorphisms in the TAS2R38 gene result in two high-frequency haplotypes associated with taste perception of the bitter compound phenylthiocarbamide (2). The “taster” haplotype codes proline-alanine-valine (PAV), and the “nontaster” haplotype codes alanine-valine-isoleucine (AVI) at positions 49, 262, and 296 in the receptor protein. Responses to AHLs in vitro are greatest in PAV/PAV epithelial cells, and this genotype is reported to be protective against P. aeruginosa in the sinonasal airway (1).

P. aeruginosa is the most frequently isolated respiratory pathogen in cystic fibrosis (CF), and chronic infection is associated with accelerated rates of disease progression. Determining the impact of TAS2R38 polymorphisms on P. aeruginosa infection in CF could have implications for patient risk stratification and, as naturally occurring and synthetic agonists to T2R38 are already in clinical use (3), could identify promising therapeutic targets.

We characterized T2R38 localization in the CF airway and investigated the hypothesis that TAS2R38 polymorphisms would modify the prevalence and impact of P. aeruginosa infection in CF. Some of the results of these studies have previously been reported in the form of abstracts.

Item Type:	Article
Identifier:	10.1164/rccm.201711-2365LE
Keywords:	Cilia, Taste receptor, type 2, Quorum sensing, Mucociliary clearance
Subjects:	Natural sciences > Cell and molecular biology Natural sciences
Depositing User:	Volker Behrends
Date Deposited:	20 May 2024 13:09
Last Modified:	20 May 2024 13:09
URI:	https://repository.uwl.ac.uk/id/eprint/11472

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