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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; Fr�d�ric Dubern, Jean-; Singh, Sonali; Muntaka, Sirina; Wheldon, Lee; Luckett, Jennifer; Tighe, Paddy; Bosquillon, Cynthia; Williams, Paul; C�mara, Miguel; Mart�nez-Pomares, Luisa


Yi-Chia Liu

Farah Hussain

Assistant Professor

Ana Pavia

Nigel Halliday

Research Development Manager

Sirina Muntaka

Lee Wheldon

Senior Research Fellow

Professor of Molecular Immunology

Professor of Molecular Microbiology

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Professor of Molecular Microbiology


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


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.

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
Public URL
Publisher URL


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