Inhibition of virulence factor expression in Staphylococcus aureus by the Staphylococcus epidermidis agr pheromone and derivatives

FEBS Letters

Otto, Michael¹  Vuong, Cuong¹  Süßmuth, Roderich²  Götz, Friedrich¹  Jung, Günther² 

[1] Mikrobielle Genetik, Universität Tübingen, Waldhäuserstr. 70/8, 72076 Tübingen, Germany;Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany

关键词: Agr;    Quorum-sensing;    Pheromone;    Staphylococcus aureus;    Staphylococcus epidermidis;    TSB;    tryptic soy broth;    Dde;    1-(4;    4-dimethyl-2;    6-dioxocyclohex-1-ylidene)ethyl;    Fmoc;    fluorenylmethoxycarbonyl;    Mmt;    p-methoxytrityl;    TFA;    trifluoroacetic acid;    TIS;    triisopropylsilane;    Trt;    trityl;   

DOI  :  10.1016/S0014-5793(99)00514-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown