title: Narrow-spectrum inhibitors of Campylobacter jejuni flagellar expression and growth.
abstract: Campylobacter jejuni is a major cause of food-borne illness due to its ability to reside within the gastrointestinal tracts of chickens. Multiple studies have identified the flagella of C. jejuni as a major determinant of chicken colonization. An inhibitor screen of approximately 147,000 small molecules was performed to identify compounds that are able to inhibit flagellar expression in a reporter strain of C. jejuni. Several compounds that modestly inhibited motility of wild-type C. jejuni in standard assays were identified, as were a number of small molecules that robustly inhibited C. jejuni growth, in vitro. Examination of similar bacterial screens found that many of these small molecules inhibited only the growth of C. jejuni. Follow-up assays demonstrated inhibition of other strains of C. jejuni and Campylobacter coli but no inhibition of the closely related Helicobacter pylori. The compounds were determined to be bacteriostatic and nontoxic to eukaryotic cells. Preliminary results from a day-of-hatch chick model of colonization suggest that at least one of the compounds demonstrates promise for reducing Campylobacter colonization loads in vivo, although further medicinal chemistry may be required to enhance bioavailability.
authors: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors: Jeremiah G
authors: JG
authors: Johnson
authors: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors: Caroline
authors: C
authors: Yuhas
authors: Center for Chemical Genomics, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors: Thomas J
authors: TJ
authors: McQuade
authors: Center for Chemical Genomics, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors: Martha J
authors: MJ
authors: Larsen
authors: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA vdirita@umich.edu.
authors: Victor J
authors: VJ
authors: DiRita
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000633:toxicity; D017000:Campylobacter coli / Q000187:drug effects; D016123:Campylobacter jejuni / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D002645:Chickens / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D005057:Eukaryotic Cells / Q000187:drug effects; D005407:Flagella / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects; D057166:High-Throughput Screening Assays; D008826:Microbial Sensitivity Tests; D011201:Poultry Diseases / Q000382:microbiology; D054852:Small Molecule Libraries; D013045:Species Specificity
chemical_list: D000900:Anti-Bacterial Agents; D054852:Small Molecule Libraries