Hamamelitannin Analogues that Modulate Quorum Sensing as Potentiators of Antibiotics against Staphylococcus aureus.
The modulation of bacterial communication to potentiate the effect of existing antimicrobial drugs is a promising alternative to the development of novel antibiotics. In the present study, we synthesized 58 analogues of hamamelitannin (HAM), a quorum sensing inhibitor and antimicrobial potentiator. These efforts resulted in the identification of an analogue that increases the susceptibility of Staphylococcus aureus towards antibiotics in vitro, in Caenorhabditis elegans, and in a mouse mammary gland infection model, without showing cytotoxicity.
Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
Arno
A
Vermote
Laboratory for Pharmaceutical Microbiology, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
Gilles
G
Brackman
Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
Martijn D P
MD
Risseeuw
Laboratory for Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsplein 1 (S7), 2610, Wilrijk, Belgium.
Bieke
B
Vanhoutte
Laboratory for Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsplein 1 (S7), 2610, Wilrijk, Belgium.
Paul
P
Cos
XStruct, Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281 S3, 9000, Ghent, Belgium.
Kristof
K
Van Hecke
Laboratory of Biochemistry, Ghent Univeristy, Salisburylaan 133, 9820, Merelbeke, Belgium.
Koen
K
Breyne
Laboratory of Biochemistry, Ghent Univeristy, Salisburylaan 133, 9820, Merelbeke, Belgium.
Evelyne
E
Meyer
Laboratory for Pharmaceutical Microbiology, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
Tom
T
Coenye
Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium. serge.vancalenbergh@ugent.be.|Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium. serge.vancalenbergh@ugent.be.
Serge
S
Van Calenbergh
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006601:Hexoses / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D053038:Quorum Sensing / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D006601:Hexoses; D005707:Gallic Acid; C093412:hamamelitannin
MRSA; antibiotics; biofilms; potentiators; quorum sensing