Synthesis and evaluation of aromatic BDSF bioisosteres on biofilm formation and colistin sensitivity in pathogenic bacteria

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 fo...

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Detalhes bibliográficos
Autores: Gómez Camacho, Andromeda Celeste|||0000-0002-0075-6903, Horgan, Conor, Yero, Daniel|||0000-0002-6234-4082, Bravo, Marc|||0000-0002-3173-2242, Daura i Ribera, Xavier|||0000-0001-9235-6730, O'Driscoll, Michelle, Gibert, Isidre|||0000-0003-1442-2258, O'Sullivan, Timothy|||0000-0001-6649-331X
Tipo de documento: artigo
Data de publicação:2023
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:ddd.uab.cat:283747
Acesso em linha:https://ddd.uab.cat/record/283747
https://dx.doi.org/urn:doi:10.1016/j.ejmech.2023.115819
Access Level:Acceso aberto
Palavra-chave:Diffusible signal factor
Quorum sensing
Biofilms
Resistance
Acinetobacter baumannii
Escherichia coli
Burkholderia multivorans
Burkholderia cepacia
Burkholderia cenocepacia
Pseudomonas aeruginosa Stenotrophomonas maltophilia
Descrição
Resumo: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.