TY - JOUR
T1 - High-throughput screening of inhibitors targeting Agr/Fsr quorum sensing in staphylococcus aureus and enterococcus faecalis
AU - Desouky, Said E.
AU - Nishiguchi, Kenzo
AU - Zendo, Takeshi
AU - Igarashi, Yasuhiro
AU - Williams, Paul
AU - Sonomoto, Kenji
AU - Nakayama, Jiro
N1 - Funding Information:
This research was supported in part by Grants-in-Aid for Scientific Research (B) nos. 2138006 and 24380050 from the Japan Society for the Promotion of Science (to J. N.) and from the Adaptable and Seamless Technology transfer Program through Target-Driven R&D (A-step) (AS232Z02064G) from the Japan Science and Technology Agency (to J. N.). We are grateful to the Ministry of Higher Education and Scientific Research of Egypt for providing a scholarship as financial support to Dr. Said E. Desouky during this study. Work in Professor Paul Williams’s laboratory was supported by the Medical Research Council, of the U.K., and this is gratefully acknowledged.
PY - 2013
Y1 - 2013
N2 - Staphylococcus aureus and Enterococcus faecalis employ cyclic peptide-mediated quorum sensing (QS) systems, termed agr and fsr respectively, to regulate the expression of a series of virulence genes. To identify quorum sensing inhibitors (QSIs) that target agr/fsr systems, an efficient screening system was established. In addition to the gelatinase-induction assay to examine E. faecalis fsr QS, the use of an S. aureus agr reporter strain that carries luciferase and green fluorescence protein genes under the agr P3 promoter facilitated the development of a high-throughput screen (HTS) for QSIs. As a result of screening of 906 actinomycetes culture extracts, four showed QSI activity against the agr and fsr systems without growth inhibitory activity. The extracts were purified on a small scale, and three HPLC peaks were obtained with obvious QSI activity. In sum, the established HTS system is a promising strategy for the discovery of anti-pathogenic agents targeting cyclic peptide-mediated QS in Gram-positive pathogens.
AB - Staphylococcus aureus and Enterococcus faecalis employ cyclic peptide-mediated quorum sensing (QS) systems, termed agr and fsr respectively, to regulate the expression of a series of virulence genes. To identify quorum sensing inhibitors (QSIs) that target agr/fsr systems, an efficient screening system was established. In addition to the gelatinase-induction assay to examine E. faecalis fsr QS, the use of an S. aureus agr reporter strain that carries luciferase and green fluorescence protein genes under the agr P3 promoter facilitated the development of a high-throughput screen (HTS) for QSIs. As a result of screening of 906 actinomycetes culture extracts, four showed QSI activity against the agr and fsr systems without growth inhibitory activity. The extracts were purified on a small scale, and three HPLC peaks were obtained with obvious QSI activity. In sum, the established HTS system is a promising strategy for the discovery of anti-pathogenic agents targeting cyclic peptide-mediated QS in Gram-positive pathogens.
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U2 - 10.1271/bbb.120769
DO - 10.1271/bbb.120769
M3 - Article
C2 - 23649251
AN - SCOPUS:84878688240
VL - 77
SP - 923
EP - 927
JO - Bioscience, Biotechnology and Biochemistry
JF - Bioscience, Biotechnology and Biochemistry
SN - 0916-8451
IS - 5
ER -