Sulfonamide-based diffusible signal factor analogs interfere with quorum sensing in Stenotrophomonas maltophilia and Burkholderia cepacia
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Accepted Version
Date
2019-08-30
Authors
Huedo, Pol
Kumar, Vydyula P.
Horgan, Conor
Yero, Daniel
Daura, Xavier
Gibert, Isidre
O'Sullivan, Timothy P.
Journal Title
Journal ISSN
Volume Title
Publisher
Future Science Group
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Abstract
Aim: Stenotrophomonas maltophilia (Sm) and Burkholderia cepacia complex (BCC) are Gram-negative bacterial pathogens, which are typically multidrug resistant and excellent biofilm producers. These phenotypes are controlled by quorum sensing (QS) systems from the diffusible signal factor (DSF) family. We aim to interfere with this QS system as an alternative approach in combatting such difficult-to-treat infections. Materials & methods: A library of sulfonamide-based DSF bioisosteres was synthesized and tested against the major phenotypes regulated by QS. Results & conclusion: Several analogs display significant
antibiofilm activity while the majority increase the action of the last-resort antibiotic colistin against Sm and BCC. Most compounds inhibit DSF synthesis in the Sm K279a strain. Our results support the strategy of interfering with QS communications to combat multidrug resistance.
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Keywords
Antimicrobials , Biofilms , Bioisosterism , Burkholderia cepacia complex , Multi drug resistance , Nosocomial pathogens , Quorum sensing (QS) , QS inhibitors , Stenotrophomonas maltophilia , Sulfonamides
Citation
Huedo, P., Kumar, V. P., Horgan, C., Yero, D., Daura, X., Gibert, I. and O'Sullivan, T. P. (2019) 'Sulfonamide-based diffusible signal factor analogs interfere with quorum sensing in Stenotrophomonas maltophilia and Burkholderia cepacia', Future Medicinal Chemistry, 11(13), pp. 1565-1582. doi: 10.4155/fmc-2019-0015
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© 2019, Future Science Group. All rights reserved.