High-throughput screening of inhibitors targeting Agr/Fsr quorum sensing in staphylococcus aureus and enterococcus faecalis

Said E. Desouky, Kenzo Nishiguchi, Takeshi Zendo, Yasuhiro Igarashi, Paul Williams, Kenji Sonomoto, Jiro Nakayama

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish
Pages (from-to)923-927
Number of pages5
JournalBioscience, Biotechnology and Biochemistry
Volume77
Issue number5
DOIs
Publication statusPublished - Jun 12 2013

Fingerprint

Quorum Sensing
Cyclic Peptides
Enterococcus faecalis
Staphylococcus aureus
Screening
Throughput
Gelatinases
Pathogens
Luciferases
Assays
Genes
Fluorescence
Proteins
Actinobacteria
Virulence
High Pressure Liquid Chromatography
Growth

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 journalArticle

Desouky, Said E. ; Nishiguchi, Kenzo ; Zendo, Takeshi ; Igarashi, Yasuhiro ; Williams, Paul ; Sonomoto, Kenji ; Nakayama, Jiro. / High-throughput screening of inhibitors targeting Agr/Fsr quorum sensing in staphylococcus aureus and enterococcus faecalis. In: Bioscience, Biotechnology and Biochemistry. 2013 ; Vol. 77, No. 5. pp. 923-927.
@article{a0e284b2f04d40e0b673713dc8b5acd0,
title = "High-throughput screening of inhibitors targeting Agr/Fsr quorum sensing in staphylococcus aureus and enterococcus faecalis",
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.",
author = "Desouky, {Said E.} and Kenzo Nishiguchi and Takeshi Zendo and Yasuhiro Igarashi and Paul Williams and Kenji Sonomoto and Jiro Nakayama",
year = "2013",
month = "6",
day = "12",
doi = "10.1271/bbb.120769",
language = "English",
volume = "77",
pages = "923--927",
journal = "Bioscience, Biotechnology and Biochemistry",
issn = "0916-8451",
publisher = "Japan Society for Bioscience Biotechnology and Agrochemistry",
number = "5",

}

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 -