Indole and 7-benzyloxyindole attenuate the virulence of Staphylococcus aureus

• Published in: Applied microbiology and biotechnology 2013-05, Vol.97 (10), p.4543-4552
• Main Authors: Lee, Jin-Hyung, Cho, Hyun Seob, Kim, Younghoon, Kim, Jung-Ae, Banskota, Suhrid, Cho, Moo Hwan, Lee, Jintae
• Format: Article
• Language: English
• Subjects: Analysis; Antibiotics; Applied Microbial and Cell Physiology; Bacteria; Bacterial infections; Base Sequence; Biofilms; Biomedical and Life Sciences; Biotechnology; Blood; Caenorhabditis elegans; Carotenoids; DNA Primers; Drug resistance; Gene expression; Genetic transcription; Health aspects; Humans; Hydrogen peroxide; Immune system; Indoles - metabolism; Life Sciences; Microbial Genetics and Genomics; Microbiology; Nematoda; Nematodes; Nosocomial infection; Nosocomial infections; Proteases; Real-Time Polymerase Chain Reaction; Staphylococcus aureus; Staphylococcus aureus - pathogenicity; Staphylococcus infections; Studies; Virulence
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-012-4674-z

Human pathogens can readily develop drug resistance due to the long-term use of antibiotics that mostly inhibit bacterial growth. Unlike antibiotics, antivirulence compounds diminish bacterial virulence without affecting cell viability and thus, may not lead to drug resistance. Staphylococcus aureus is a major agent of nosocomial infections and produces diverse virulence factors, such as the yellow carotenoid staphyloxanthin, which promotes resistance to reactive oxygen species (ROS) and the host immune system. To identify novel antivirulence compounds, bacterial signal indole present in animal gut and diverse indole derivatives were investigated with respect to reducing staphyloxanthin production and the hemolytic activity of S. aureus . Treatment with indole or its derivative 7-benzyloxyindole (7BOI) caused S. aureus to become colorless and inhibited its hemolytic ability without affecting bacterial growth. As a result, S. aureus was more easily killed by hydrogen peroxide (H 2 O 2 ) and by human whole blood in the presence of indole or 7BOI. In addition, 7BOI attenuated S. aureus virulence in an in vivo model of nematode Caenorhabditis elegans , which is readily infected and killed by S. aureus . Transcriptional analyses showed that both indole and 7BOI repressed the expressions of several virulence genes such as α-hemolysin gene hla , enterotoxin seb , and the protease genes splA and sspA and modulated the expressions of the important regulatory genes agrA and sarA . These findings show that indole derivatives are potential candidates for use in antivirulence strategies against persistent S. aureus infection.