Sulfonamide-based diffusible signal factor analogs interfere with quorum sensing in Stenotrophomonas maltophilia and Burkholderia cepacia

Pol Huedo; Vydyula P. Kumar; Conor Horgan; Daniel Yero; Xavier Daura; Isidre Gibert; Timothy P. O'sullivan

doi:10.4155/fmc-2019-0015

Sulfonamide-based diffusible signal factor analogs interfere with quorum sensing in Stenotrophomonas maltophilia and Burkholderia cepacia

Pol Huedo, Vydyula P. Kumar, Conor Horgan, Daniel Yero, Xavier Daura, Isidre Gibert^*, Timothy P. O'sullivan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research

7 Citations (Scopus)

Abstract

© 2019 Newlands Press. 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.

Original language	English
Pages (from-to)	1565-1582
Number of pages	18
Journal	Future Medicinal Chemistry
Volume	11
Issue number	13
DOIs	https://doi.org/10.4155/fmc-2019-0015
Publication status	Published - Jul 2019

Keywords

antimicrobials
biofilms
bioisosterism
Burkholderia cepacia complex
multidrug resistance
nosocomial pathogens
QS inhibitors
quorum sensing (QS)
Stenotrophomonas maltophilia
sulfonamides

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@article{2a81fcf4327645b9a727f961bdb1e9b0,

title = "Sulfonamide-based diffusible signal factor analogs interfere with quorum sensing in Stenotrophomonas maltophilia and Burkholderia cepacia",

abstract = "{\textcopyright} 2019 Newlands Press. 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.",

keywords = "antimicrobials, biofilms, bioisosterism, Burkholderia cepacia complex, multidrug resistance, nosocomial pathogens, QS inhibitors, quorum sensing (QS), Stenotrophomonas maltophilia, sulfonamides",

author = "Pol Huedo and Kumar, {Vydyula P.} and Conor Horgan and Daniel Yero and Xavier Daura and Isidre Gibert and O'sullivan, {Timothy P.}",

year = "2019",

month = jul,

doi = "10.4155/fmc-2019-0015",

language = "English",

volume = "11",

pages = "1565--1582",

journal = "Future Medicinal Chemistry",

issn = "1756-8919",

publisher = "Future Science",

number = "13",

}

TY - JOUR

T1 - Sulfonamide-based diffusible signal factor analogs interfere with quorum sensing in Stenotrophomonas maltophilia and Burkholderia cepacia

AU - Huedo, Pol

AU - Kumar, Vydyula P.

AU - Horgan, Conor

AU - Yero, Daniel

AU - Daura, Xavier

AU - Gibert, Isidre

AU - O'sullivan, Timothy P.

PY - 2019/7

Y1 - 2019/7

N2 - © 2019 Newlands Press. 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.

AB - © 2019 Newlands Press. 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.

KW - antimicrobials

KW - biofilms

KW - bioisosterism

KW - Burkholderia cepacia complex

KW - multidrug resistance

KW - nosocomial pathogens

KW - QS inhibitors

KW - quorum sensing (QS)

KW - Stenotrophomonas maltophilia

KW - sulfonamides

UR - http://www.mendeley.com/research/sulfonamidebased-diffusible-signal-factor-analogs-interfere-quorum-sensing-stenotrophomonas-maltophi

U2 - 10.4155/fmc-2019-0015

DO - 10.4155/fmc-2019-0015

M3 - Article

C2 - 31469336

SN - 1756-8919

VL - 11

SP - 1565

EP - 1582

JO - Future Medicinal Chemistry

JF - Future Medicinal Chemistry

IS - 13

ER -

Sulfonamide-based diffusible signal factor analogs interfere with quorum sensing in Stenotrophomonas maltophilia and Burkholderia cepacia

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Keywords

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