Contribution of the alkylquinolone quorum sensing system to the interaction of Pseudomonas aeruginosa with bronchial epithelial cells.

Liu, Yi-Chia; Hussain, Farah; Negm, Ola; Pavia, Ana; Halliday, Nigel; Singh, Sonali; Muntaka, Sirina; Wheldon, Lee; Luckett, Jennifer; Tighe, Paddy; Bosquillon, Cynthia; Williams, Paul

doi:10.3389/fmicb.2018.03018

Contribution of the alkylquinolone quorum sensing system to the interaction of Pseudomonas aeruginosa with bronchial epithelial cells.

Authors

Yi-Chia Liu

Farah Hussain

OLA NEGM ola.negm@nottingham.ac.uk
Assistant Professor

Ana Pavia

Nigel Halliday

JEAN DUBERN jean.dubern@nottingham.ac.uk
Research Fellow

SONALI SINGH SONALI.SINGH@NOTTINGHAM.AC.UK
Research Development Manager

Sirina Muntaka

Lee Wheldon

JENI LUCKETT JENI.LUCKETT@NOTTINGHAM.AC.UK
Senior Research Fellow

PATRICK TIGHE paddy.tighe@nottingham.ac.uk
Professor of Molecular Immunology

CYNTHIA BOSQUILLON cynthia.bosquillon@nottingham.ac.uk
Assistant Professor

PAUL WILLIAMS paul.williams@nottingham.ac.uk
Professor of Molecular Microbiology

MIGUEL CAMARA Miguel.Camara@nottingham.ac.uk
Professor of Molecular Microbiology

LUISA MARTINEZ-POMARES luisa.m@nottingham.ac.uk
Associate Professor

Abstract

Pseudomonas aeruginosa causes infections in patients with compromised epithelial 32 barrier function. Multiple virulence factors produced by P. aeruginosa are controlled 33 by quorum sensing (QS) via 2-alkyl-4(1H)-quinolone (AQ) signal molecules. Here we 34 investigated the impact of AQs on P. aeruginosa PAO1 infection of differentiated 35 human bronchial epithelial cells (HBECs). The pqsA-E operon is responsible for the 36 biosynthesis of AQs including the 2-alkyl-3-hydroxy-4-quinolones, 4-hydroxy-2-37 alkylquinolines and 4-hydroxy-2-alkylquinoline N-oxides as exemplified by PQS, 38 HHQ and HQNO, respectively. PQS and HHQ both act as QS signal molecules while 39 HQNO is a cytochrome inhibitor. PqsE contributes both to AQ biosynthesis and 40 promotes virulence in a PQS-independent manner. Our results show that PQS, HHQ 41 and HQNO were produced during PAO1 infection of HBECs, but no differences in 42 growth or cytotoxicity were apparent when PAO1 and an AQ-negative ?pqsA mutant 43 were compared. Both strains promoted synthesis of inflammatory cytokines TNF-?, 44 interleukin (IL)-6 and IL-17C by HBECs and provision of exogenous PQS negatively 45 impacted on this response without affecting bacterial growth. Expression of pqsE and 46 the PQS-independent PqsE-regulated genes mexG and lecA was detected during HBEC 47 infection. Levels were reduced in the ?pqsA mutant, i.e. in the absence of PQS, and 48 increased by exogenous PQS. These results support an AQ-independent role for PqsE 49 during initial infection of HBEC by P. aeruginosa and for PQS as an enhancer of PqsE 50 and PqsE-controlled virulence determinants and as an immunomodulator

Citation

Liu, Y., Hussain, F., Negm, O., Pavia, A., Halliday, N., Frédéric Dubern, J., …Martínez-Pomares, L. (2018). Contribution of the alkylquinolone quorum sensing system to the interaction of Pseudomonas aeruginosa with bronchial epithelial cells. Frontiers in Microbiology, 9, Article 3018. https://doi.org/10.3389/fmicb.2018.03018

Journal Article Type	Article
Acceptance Date	Nov 22, 2018
Online Publication Date	Dec 18, 2018
Publication Date	Dec 18, 2018
Deposit Date	Nov 30, 2018
Publicly Available Date	Nov 30, 2018
Electronic ISSN	1664-302X
Publisher	Frontiers Media
Peer Reviewed	Peer Reviewed
Volume	9
Article Number	3018
DOI	https://doi.org/10.3389/fmicb.2018.03018
Public URL	https://nottingham-repository.worktribe.com/output/1349470
Publisher URL	https://www.frontiersin.org/articles/10.3389/fmicb.2018.03018/full