Inhibition of virulence factor expression in Staphylococcus aureus by the Staphylococcus epidermidis agr pheromone and derivatives.
The agr quorum-sensing system in Staphylococci controls the production of surface proteins and exoproteins. In the pathogenic species Staphylococcus aureus, these proteins include many virulence factors. The extracellular signal of the quorum-sensing system is a thiolactone-containing peptide pheromone, whose sequence varies among the different staphylococcal strains. We demonstrate that a synthetic Staphylococcus epidermidis pheromone is a competent inhibitor of the Staphylococcus aureus agr system. Derivatives of the pheromone, in which the N-terminus or the cyclic bond structure was changed, were synthesized and their biological activity was determined. The presence of a correct N-terminus and a thiolactone were absolute prerequisites for an agr-activating effect in S. epidermidis, whereas inhibition of the S. aureus agr system was less dependent on the original structure. Our results show that effective quorum-sensing blockers that suppress the expression of virulence factors in S. aureus can be designed based on the S. epidermidis pheromone.
Otto
M
M
Mikrobielle Genetik, Universität Tübingen, Germany. michael.otto@uni-tuebingen.de
Süssmuth
R
R
Vuong
C
C
Jung
G
G
Götz
F
F
D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000737:chemistry; D015394:Molecular Structure; D009842:Oligopeptides; D010641:Phenotype; D010675:Pheromones / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000737:chemistry; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity; D013212:Staphylococcus epidermidis / Q000378:metabolism*; D015534:Trans-Activators; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000737:chemistry; D014774:Virulence
C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D009842:Oligopeptides; D010675:Pheromones; D015534:Trans-Activators; D014157:Transcription Factors