Thiophenone Attenuates Enteropathogenic Escherichia coli O103:H2 Virulence by Interfering with AI-2 Signaling.
Interference with bacterial quorum sensing communication provides an anti-virulence strategy to control pathogenic bacteria. Here, using the Enteropathogenic E. coli (EPEC) O103:H2, we showed for the first time that thiophenone TF101 reduced expression of lsrB; the gene encoding the AI-2 receptor. Combined results of transcriptional and phenotypic analyses suggested that TF101 interfere with AI-2 signalling, possibly by competing with AI-2 for binding to LsrB. This is supported by in silico docking prediction of thiophenone TF101 in the LsrB pocket. Transcriptional analyses furthermore showed that thiophenone TF101 interfered with expression of the virulence genes eae and fimH. In addition, TF101 reduced AI-2 induced E. coli adhesion to colorectal adenocarcinoma cells. TF101, on the other hand, did not affect epinephrine or norepinephrine enhanced E. coli adhesion. Overall, our results showed that thiophenone TF101 interfered with virulence expression in E. coli O103:H2, suggestedly by interfering with AI-2 mediated quorum sensing. We thus conclude that thiophenone TF101 might represent a promising future anti-virulence agent in the fight against pathogenic E. coli.
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Ingun Lund
http://orcid.org/0000-0002-6446-1768
IL
Witsø
Nordic Institute of Dental Materials (NIOM), Oslo, Norway.
Håkon
H
Valen Rukke
Department of Chemistry, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
Tore
T
Benneche
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Anne
A
Aamdal Scheie
D018829:Adhesins, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018830:Adhesins, Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D001665:Binding Sites; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D054308:Enteropathogenic Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D004837:Epinephrine / Q000494:pharmacology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D036781:Fimbriae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006714:Homoserine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000037:antagonists & inhibitors* / Q000378:metabolism; D062105:Molecular Docking Simulation; D009638:Norepinephrine / Q000494:pharmacology; D011485:Protein Binding; D053038:Quorum Sensing / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*; D014774:Virulence
D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D007783:Lactones; C555903:LsrB protein, E coli; C091088:N-octanoylhomoserine lactone; D011956:Receptors, Cell Surface; D013876:Thiophenes; C058769:fimH protein, E coli; C073819:eaeA protein, E coli; D036781:Fimbriae Proteins; D006714:Homoserine; D009638:Norepinephrine; D004837:Epinephrine