Synthesis and evaluation of aromatic BDSF bioisosteres on biofilm formation and colistin sensitivity in pathogenic bacteria
Gómez Camacho, Andromeda Celeste (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Horgan, Conor (University College Cork)
Yero, Daniel (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Bravo, Marc (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Daura i Ribera, Xavier (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
O'Driscoll, Michelle (University College Cork)
Gibert, Isidre (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
O'Sullivan, Timothy (University College Cork)

Date:	2023
Abstract:	The diffusible signal factor family (DSF) of molecules play an important role in regulating intercellular communication, or quorum sensing, in several disease-causing bacteria. These messenger molecules, which are comprised of cis-unsaturated fatty acids, are involved in the regulation of biofilm formation, antibiotic tolerance, virulence and the control of bacterial resistance. We have previously demonstrated how olefinic N-acyl sulfonamide bioisosteric analogues of diffusible signal factor can reduce biofilm formation or enhance antibiotic sensitivity in a number of bacterial strains. This work describes the design and synthesis of a second generation of aromatic N-acyl sulfonamide bioisosteres. The impact of these compounds on biofilm production in Acinetobacter baumannii, Escherichia coli, Burkholderia multivorans, Burkholderia cepacia, Burkholderia cenocepacia, Pseudomonas aeruginosa and Stenotrophomonas maltophilia is evaluated, in addition to their effects on antibiotic tolerance. The ability of these molecules to increase survival rates on co-administration with colistin is also investigated using the Galleria infection model.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00092 Agencia Estatal de Investigación PID2019-111364RB-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Diffusible signal factor ; Quorum sensing ; Biofilms ; Resistance ; Acinetobacter baumannii ; Escherichia coli ; Burkholderia multivorans ; Burkholderia cepacia ; Burkholderia cenocepacia ; Pseudomonas aeruginosa Stenotrophomonas maltophilia
Published in:	European Journal of Medicinal Chemistry, Vol. 261 (December 2023) , art. 115819, ISSN 1768-3254

DOI: 10.1016/j.ejmech.2023.115819

16 p, 1.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles