Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 923-927 |
| Number of pages | 5 |
| Journal | Bioscience, Biotechnology and Biochemistry |
| Volume | 77 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Jun 12 2013 |
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All Science Journal Classification (ASJC) codes
- Biotechnology
- Analytical Chemistry
- Biochemistry
- Applied Microbiology and Biotechnology
- Molecular Biology
- Organic Chemistry
Cite this
High-throughput screening of inhibitors targeting Agr/Fsr quorum sensing in staphylococcus aureus and enterococcus faecalis. / Desouky, Said E.; Nishiguchi, Kenzo; Zendo, Takeshi; Igarashi, Yasuhiro; Williams, Paul; Sonomoto, Kenji; Nakayama, Jiro.
In: Bioscience, Biotechnology and Biochemistry, Vol. 77, No. 5, 12.06.2013, p. 923-927.Research output: Contribution to journal › Article
}
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
PY - 2013/6/12
Y1 - 2013/6/12
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.
UR - http://www.scopus.com/inward/record.url?scp=84878688240&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878688240&partnerID=8YFLogxK
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 -