Pseudomonas aeruginosa Toxin ExoU as a Therapeutic Target in the Treatment of Bacterial Infections

Foulkes, Daniel M.; McLean, Keri; Haneef, Atikah S.; Fernig, David G.; Winstanley, Craig; Berry, Neil; Kaye, Stephen B.

doi:10.3390/microorganisms7120707

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Pseudomonas aeruginosa Toxin ExoU as a Therapeutic Target in the Treatment of Bacterial Infections

by

Daniel M. Foulkes

^1,2,*,

Keri McLean

^1,3,*

,

Atikah S. Haneef

¹,

David G. Fernig

²,

Craig Winstanley

⁴,

Neil Berry

⁵

and

Stephen B. Kaye

^1,3

¹

Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK

²

Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK

³

St. Paul’s Eye Unit, Royal Liverpool University Hospital, Liverpool L7 8XP, UK

⁴

Department of Clinical Infection, Institute of Infection and Global Health, University of Liverpool, Liverpool L6 97B, UK

⁵

Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK

^*

Authors to whom correspondence should be addressed.

Microorganisms 2019, 7(12), 707; https://doi.org/10.3390/microorganisms7120707

Submission received: 16 October 2019 / Revised: 10 December 2019 / Accepted: 14 December 2019 / Published: 16 December 2019

(This article belongs to the Special Issue Insights Into The Molecular Pathogenesis of Ocular Infections)

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Abstract

The opportunistic pathogen Pseudomonas aeruginosa employs the type III secretion system (T3SS) and four effector proteins, ExoS, ExoT, ExoU, and ExoY, to disrupt cellular physiology and subvert the host’s innate immune response. Of the effector proteins delivered by the T3SS, ExoU is the most toxic. In P. aeruginosa infections, where the ExoU gene is expressed, disease severity is increased with poorer prognoses. This is considered to be due to the rapid and irreversible damage exerted by the phospholipase activity of ExoU, which cannot be halted before conventional antibiotics can successfully eliminate the pathogen. This review will discuss what is currently known about ExoU and explore its potential as a therapeutic target, highlighting some of the small molecule ExoU inhibitors that have been discovered from screening approaches.

Keywords: Pseudomonas aeruginosa; ExoU; type 3 secretion system; inhibitor; non-antibiotic antimicrobials

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MDPI and ACS Style

Foulkes, D.M.; McLean, K.; Haneef, A.S.; Fernig, D.G.; Winstanley, C.; Berry, N.; Kaye, S.B. Pseudomonas aeruginosa Toxin ExoU as a Therapeutic Target in the Treatment of Bacterial Infections. Microorganisms 2019, 7, 707. https://doi.org/10.3390/microorganisms7120707

AMA Style

Foulkes DM, McLean K, Haneef AS, Fernig DG, Winstanley C, Berry N, Kaye SB. Pseudomonas aeruginosa Toxin ExoU as a Therapeutic Target in the Treatment of Bacterial Infections. Microorganisms. 2019; 7(12):707. https://doi.org/10.3390/microorganisms7120707

Chicago/Turabian Style

Foulkes, Daniel M., Keri McLean, Atikah S. Haneef, David G. Fernig, Craig Winstanley, Neil Berry, and Stephen B. Kaye. 2019. "Pseudomonas aeruginosa Toxin ExoU as a Therapeutic Target in the Treatment of Bacterial Infections" Microorganisms 7, no. 12: 707. https://doi.org/10.3390/microorganisms7120707

APA Style

Foulkes, D. M., McLean, K., Haneef, A. S., Fernig, D. G., Winstanley, C., Berry, N., & Kaye, S. B. (2019). Pseudomonas aeruginosa Toxin ExoU as a Therapeutic Target in the Treatment of Bacterial Infections. Microorganisms, 7(12), 707. https://doi.org/10.3390/microorganisms7120707

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Pseudomonas aeruginosa Toxin ExoU as a Therapeutic Target in the Treatment of Bacterial Infections

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