title: Altering the communication networks of multispecies microbial systems using a diverse toolbox of AI-2 analogues.
abstract: There have been intensive efforts to find small molecule antagonists for bacterial quorum sensing (QS) mediated by the "universal" QS autoinducer, AI-2. Previous work has shown that linear and branched acyl analogues of AI-2 can selectively modulate AI-2 signaling in bacteria. Additionally, LsrK-dependent phosphorylated analogues have been implicated as the active inhibitory form against AI-2 signaling. We used these observations to synthesize an expanded and diverse array of AI-2 analogues, which included aromatic as well as cyclic C-1-alkyl analogues. Species-specific analogues that disrupted AI-2 signaling in Escherichia coli and Salmonella typhimurium were identified. Similarly, analogues that disrupted QS behaviors in Pseudomonas aeruginosa were found. Moreover, we observed a strong correlation between LsrK-dependent phosphorylation of these acyl analogues and their ability to suppress QS. Significantly, we demonstrate that these analogues can selectively antagonize QS in single bacterial strains in a physiologically relevant polymicrobial culture.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.
authors.forename: Sonja
authors.initials: S
authors.lastname: Gamby
authors.forename: Varnika
authors.initials: V
authors.lastname: Roy
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.forename: Jacqueline A I
authors.initials: JA
authors.lastname: Smith
authors.forename: Jingxin
authors.initials: J
authors.lastname: Wang
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Stewart
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: William E
authors.initials: WE
authors.lastname: Bentley
authors.forename: Herman O
authors.initials: HO
authors.lastname: Sintim
mesh_terms: D004926:Escherichia coli / Q000201:enzymology / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D006714:Homoserine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D053038:Quorum Sensing; D012097:Repressor Proteins / Q000378:metabolism; D012486:Salmonella typhimurium / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D007783:Lactones; C504601:LsrR protein, E coli; C091088:N-octanoylhomoserine lactone; D012097:Repressor Proteins; D006714:Homoserine; C549217:LsrK protein, E coli; D017853:Phosphotransferases (Alcohol Group Acceptor); D001616:beta-Galactosidase