Discovery of cephalosporin-3´-diazeniumdiolates that show dual antibacterial and antibiofilm effects against Pseudomonas aeruginosa clinical cystic fibrosis isolates and efficacy in a Murine Respiratory Infection Model

Accepted/In Press date: 24 April 2020

e-pub ahead of print date: 24 April 2020

Published date: 12 June 2020

Additional Information: Funding Information: M.J.K. and S.A.R. thank the Australian Cystic Fibrosis Research Trust (ACFRT) for generously funding this work. We also thank the National Institutes for Allergy and Infectious Diseases (NIAID, USA) for their contributions to MIC testing and Lynn Miesel and her team at Pharmacology Discovery Services (Eurofins) Taiwan Ltd. for performing the mouse respiratory infection model. V.R., W.H.P., and S.A.R. acknowledge financial support from the Singapore Centre for Environmental Life Sciences Engineering, whose research is supported by the National Research Foundation Singapore, Ministry of Education, Nanyang Technological University and National University of Singapore, under its Research Centre of Excellence Programme. Antibacterial screening performed by CO-ADD (The Community for Antimicrobial Drug Discovery) was funded by the Wellcome Trust (UK) and The University of Queensland (Australia). CO-ADD acknowledges Compounds Australia ( griffith.edu.au/griffith-sciences/compounds-australia ) for their provision of specialized compound management and logistics research services to the project, ACRF and NCRIS for their funding support of the facility, and the Australian Red Cross Blood Service for the supply of blood for haemolysis assays. M.A.T.B., A.G.E., and J.Z. were supported in part by Wellcome Trust Strategic Award 104797/Z/14/Z. M.A.C. is a NHMRC Principal Research Fellow (APP1059354) and holds a fractional professorial research fellow appointment at The University of Queensland, with his remaining time as CEO of Inflazome Ltd., a company developing drugs to address clinical unmet needs in inflammatory disease. G.M.C. acknowledges funding from the New Zealand Health Research Council. O.S., S.N.F., and J.S.W. receive support from the NIHR Southampton Biomedical Research Centre and NIHR Southampton Clinical Research Facility and from the UK National Biofilm Innovation Centre, an Innovation and Knowledge Centre funded by the Biotechnology and Biological Sciences Research Council, Innovate UK, and Hartree Centre (Award Number BB/R012415/1). Publisher Copyright: © 2020 American Chemical Society.

Keywords: Pseudomonas aeruginosa, biofilm, cephalosporin-3′-diazeniumdiolate, chronic infection, cystic fibrosis

Local EPrints ID: 439757

URI: http://eprints.soton.ac.uk/id/eprint/439757

DOI: doi:10.1021/acsinfecdis.0c00070

ISSN: 2373-8227

PURE UUID: e45320ea-9548-453e-b204-996df4361307

ORCID for Myron Christodoulides: orcid.org/0000-0002-9663-4731

ORCID for Saul N. Faust: orcid.org/0000-0003-3410-7642

ORCID for Jeremy S. Webb: orcid.org/0000-0003-2068-8589

Date deposited: 01 May 2020 16:37

Last modified: 17 Mar 2024 05:31