title: 7-fluoroindole as an antivirulence compound against Pseudomonas aeruginosa.
abstract: The emergence of antibiotic resistance has necessitated new therapeutic approaches for combating persistent bacterial infection. An alternative approach is regulation of bacterial virulence instead of growth suppression, which can readily lead to drug resistance. The virulence of the opportunistic human pathogen Pseudomonas aeruginosa depends on a large number of extracellular factors and biofilm formation. Thirty-one natural and synthetic indole derivatives were screened. 7-fluoroindole (7FI) was identified as a compound that inhibits biofilm formation and blood hemolysis without inhibiting the growth of planktonic P. aeruginosa cells. Moreover, 7FI markedly reduced the production of quorum-sensing (QS)-regulated virulence factors 2-heptyl-3-hydroxy-4(1H)-quinolone, pyocyanin, rhamnolipid, two siderophores, pyoverdine and pyochelin. 7FI clearly suppressed swarming motility, protease activity and the production of a polymeric matrix in P. aeruginosa. However, unlike natural indole compounds, synthetic 7FI did not increase antibiotic resistance. Therefore, 7FI is a potential candidate for use in an antivirulence approach against persistent P. aeruginosa infection.
authors.affiliation: School of Chemical Engineering, Yeungnam University, Gyeongsan, South Korea.
authors.forename: Jin-Hyung
authors.initials: JH
authors.lastname: Lee
authors.forename: Yong-Guy
authors.initials: YG
authors.lastname: Kim
authors.forename: Moo Hwan
authors.initials: MH
authors.lastname: Cho
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Kim
authors.forename: Jintae
authors.initials: J
authors.lastname: Lee
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D018441:Biofilms / Q000187:drug effects; D017611:Fluorine Compounds / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity*; D037521:Virulence Factors / Q000037:antagonists & inhibitors*
chemical_list: D000900:Anti-Bacterial Agents; D017611:Fluorine Compounds; D007211:Indoles; D037521:Virulence Factors