Screening of Natural Product Derivatives Identifies Two Structurally Related Flavonoids as Potent Quorum Sensing Inhibitors against Gram-Negative Bacteria

International Journal of Molecular Sciences
Suvi Manner, Adyary Fallarero

Abstract

Owing to the failure of conventional antibiotics in biofilm control, alternative approaches are urgently needed. Inhibition of quorum sensing (QS) represents an attractive target since it is involved in several processes essential for biofilm formation. In this study, a compound library of natural product derivatives (n = 3040) was screened for anti-quorum sensing activity using Chromobacterium violaceum as reporter bacteria. Screening assays, based on QS-mediated violacein production and viability, were performed in parallel to identify non-bactericidal QS inhibitors (QSIs). Nine highly active QSIs were identified, while 328 compounds were classified as moderately actives and 2062 compounds as inactives. Re-testing of the highly actives at a lower concentration against C. violaceum, complemented by a literature search, led to the identification of two flavonoid derivatives as the most potent QSIs, and their impact on biofilm maturation in Escherichia coli and Pseudomonas aeruginosa was further investigated. Finally, effects of these leads on swimming and swarming motility of P. aeruginosa were quantified. The identified flavonoids affected all the studied QS-related functions at micromolar concentrations. These compounds can s...Continue Reading

References

Sep 1, 1990·The Journal of Infectious Diseases·C C Kuo, J T Grayston
Nov 1, 1996·Journal of Bacteriology·M GivskovS Kjelleberg
Apr 3, 2001·Applied and Environmental Microbiology·T R De KievitB H Iglewski
Sep 7, 2001·Annual Review of Microbiology·M B Miller, B L Bassler
Apr 5, 2002·Microbiology·Michael ManefieldMichael Givskov
Nov 28, 2002·Pharmacology & Therapeutics·Bent H Havsteen
Mar 5, 2003·Current Opinion in Microbiology·Roger S Smith, Barbara H Iglewski
Jul 26, 2003·The EMBO Journal·Morten HentzerMichael Givskov
May 8, 2004·Molecular Microbiology·Brian M M Ahmer
Feb 18, 2005·Journal of Bacteriology·Thomas Bovbjerg RasmussenMichael Givskov
Oct 11, 2005·Annual Review of Cell and Developmental Biology·Christopher M Waters, Bonnie L Bassler
Oct 21, 2005·Journal of Bacteriology·Nicky C CaiazzaG A O'Toole
Dec 3, 2005·International Journal of Antimicrobial Agents·T P Tim Cushnie, Andrew J Lamb
Mar 1, 2006·International Journal of Medical Microbiology : IJMM·Thomas B Rasmussen, Michael Givskov
May 19, 2006·Letters in Applied Microbiology·J H ChooJ-K Hwang
Oct 5, 2006·Analytical and Bioanalytical Chemistry·Diane McDougaldStaffan Kjelleberg
Dec 13, 2006·Microbiology and Molecular Biology Reviews : MMBR·Juan E González, Neela D Keshavan
Apr 4, 2007·Expert Review of Anti-infective Therapy·Vanessa Sperandio
May 15, 2007·Fitoterapia·D A VattemR J C McLean
Mar 6, 2008·FEMS Microbiology Letters·Tetsuyoshi InoueKazuhiro Fukui
Jul 23, 2008·Antimicrobial Agents and Chemotherapy·Mette E SkindersoeMichael Givskov
Dec 17, 2008·Journal of Bacteriology·David G Davies, Cláudia N H Marques
Aug 28, 2009·Letters in Applied Microbiology·S F BodiniF Santori
Feb 25, 2010·Natural Product Reports·Jeroen S Dickschat
Mar 23, 2011·Antimicrobial Agents and Chemotherapy·Gilles BrackmanTom Coenye
May 17, 2011·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Young Soo KimKi Hun Park
Jan 10, 2012·Archives of Medical Research·Sybiya Vasantha Packiavathy Issac AbrahamVeera Ravi Arumugam
Feb 9, 2012·Antimicrobial Agents and Chemotherapy·Tim Holm JakobsenMichael Givskov
Feb 23, 2012·Antimicrobial Agents and Chemotherapy·César de la Fuente-NúñezRobert E W Hancock
Apr 27, 2012·Journal of Agricultural and Food Chemistry·Pilar TruchadoAna Allende
Sep 19, 2012·Journal of Computer-aided Molecular Design·Angusamy AnnapooraniArumugam Veera Ravi
Nov 6, 2012·Cold Spring Harbor Perspectives in Medicine·Steven T Rutherford, Bonnie L Bassler
Nov 13, 2012·Biotechnology Advances·Vipin Chandra Kalia

❮ Previous
Next ❯

Citations

Nov 14, 2019·International Journal of Molecular Sciences·Dmitry DeryabinGalimjan Duskaev
Nov 27, 2019·Applied Microbiology and Biotechnology·Fazlurrahman KhanYoung-Mog Kim
Sep 29, 2020·Expert Opinion on Therapeutic Patents·Simone CarradoriFrancesca Sisto

❮ Previous
Next ❯

Methods Mentioned

BETA
light microscopy
Nuclear Magnetic Resonance spectroscopy
Electrophoresis
scraping

Software Mentioned

Graphpad Prism
SkanIt RE

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Biofilms

Biofilms are adherent bacterial communities embedded in a polymer matrix and can cause persistent human infections that are highly resistant to antibiotics. Discover the latest research on Biofilms here.

Biofilm & Infectious Disease

Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections.Here is the latest research on biofilm and infectious diseases.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.