Such communication helps patients and their partner(s) make an informed choice about HIV risk. “
“Pseudomonas aeruginosa secretes membrane vesicles (MVs) that deliver several virulence factors as a cargo. We found that indole and its derivative compounds, including 4-hydroxyindole, 5-hydroxyindole, Vincristine 6-hydroxyindole and isatin, repress MV production significantly. These compounds also repressed the synthesis of Pseudomonas quinolone signal (PQS), which is one of the quorum-sensing signals that upregulate virulence gene expression and positively control MV production. Moreover, we showed that other bicyclic compounds, including 1-naphthol, 2-naphthol, 2,3-dihydroxynaphthalene, 1-aminonaphthalene and 8-quinolinol,

significantly

repress MV production and PQS synthesis. In conclusion, we provide new information about the chemical structures that inhibit P. aeruginosa virulence. Pseudomonas aeruginosa is a ubiquitous bacterium that can be found in various environments. At the same time, it is known as a major opportunistic human pathogen, which secretes a wide variety of virulence factors. Many secreted virulence factors, including phospholipase C, alkaline H 89 clinical trial phosphatase, proelastase and hemolysin, are enriched in membrane vesicles (MVs) in P. aeruginosa (Kadurugamuwa & Beveridge, 1995). MVs are bilayered spheres ranging from 50 to 250 nm in diameter and are released from the outer membrane of a large number of pathogenic and nonpathogenic Gram-negative bacteria. Pseudomonas aeruginosa MVs deliver virulence factors directly into the

host cell cytoplasm and contribute to the inflammatory response during infection (Bauman & Kuehn, 2009; Bomberger et al., 2009). In addition, P. aeruginosa MVs also play a role in virulence against other bacteria (Kadurugamuwa & Beveridge, 1996). Pseudomonas aeruginosa MVs interact with both Gram-negative and -positive bacteria and possess antimicrobial activities against them (Li et al., 1998; Mashburn & Whiteley, 2005). It is likely that these predatory MVs mediate lysis of competing bacteria in polymicrobial communities. MVs also play a role as a mediator of cell–cell communication. Pseudomonas aeruginosa secretes the compound 2-heptyl-3-hydroxy-4-quinolone, referred to as Pseudomonas Lonafarnib datasheet quinolone signal (PQS: Fig. 1). PQS is not only packaged in MVs for its transportation but also induces MV production by a strong interaction with lipopolysaccharides (Mashburn & Whiteley, 2005; Mashburn-Warren et al., 2008). PQS is known as one of the quorum-sensing (QS) molecules in P. aeruginosa, which control the production of numerous extracellular virulence factors and biofilm formation (Pesci et al., 1999; Diggle et al., 2003), in addition to two acyl-homoserine lactone (HSL) molecules including N-(3-oxododecanoyl)-l-HSL (3-oxo-C12-HSL) and N-butyryl-l-HSL (C4-HSL) (Parsek & Greenberg, 2000; Singh et al., 2000).