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Campylobacter  is a leading cause of foodborne bacterial gastroenteritis worldwide and infections can be fatal. The emergence of antibiotic-resistant  Campylobacter  spp. necessitates the development of new antimicrobials. We identified novel anti- Campylobacter  small molecule inhibitors using a high throughput growth inhibition assay. To expedite screening, we made use of a “bioactive” library of 4182 compounds that we have previously shown to be active against diverse microbes. Screening for growth inhibition of  Campylobacter jejuni , identified 781 compounds that were either bactericidal or bacteriostatic at a concentration of 200 μM. Seventy nine of the bactericidal compounds were prioritized for secondary screening based on their physico-chemical properties. Based on the minimum inhibitory concentration against a diverse range of  C. jejuni  and a lack of effect on gut microbes, we selected 12 compounds. No resistance was observed to any of these 12 lead compounds when  C. jejuni  was cultured with lethal or sub-lethal concentrations suggesting that  C. jejuni  is less likely to develop resistance to these compounds. Top 12 compounds also possessed low cytotoxicity to human intestinal epithelial cells (Caco-2 cells) and no hemolytic activity against sheep red blood cells. Next, these 12 compounds were evaluated for ability to clear  C. jejuni in vitro . A total of 10 compounds had an anti- C. jejuni  effect in Caco-2 cells with some effective even at 25 μM concentrations. These novel 12 compounds belong to five established antimicrobial chemical classes; piperazines, aryl amines, piperidines, sulfonamide, and pyridazinone. Exploitation of analogs of these chemical classes may provide  Campylobacter  specific drugs that can be applied in both human and animal medicine.

Novel Anti-Campylobacter Compounds Identified Using High Throughput Screening of a Pre-selected Enriched Small Molecules Library