%0 Journal Article
%T Novel narrow spectrum benzyl thiophene sulfonamide derivatives to control Campylobacter
%J -
%D 2019
%R https://doi.org/10.1038/s41429-019-0168-x
%X Campylobacter is a leading cause of bacterial foodborne gastroenteritis worldwide, and poultry are a major source of human campylobacteriosis. The control of Campylobacter from farm to fork is challenging due to emergence of microbial resistance and lack of effective control methods. We identified a benzyl thiophene sulfonamide based small molecule (compound 1) with a minimal inhibitory concentration (MIC) of 100£¿¦ÌM against Campylobacter jejuni 81¨C176 and Campylobacter coli ATCC33559, good drug-like properties, and low toxicity on eukaryotic cells. Compound 1 was used as a lead for the preparation of 13 analogues. Two analogues, compounds 4 and 8 (TH-4 and TH-8), were identified with better antimicrobial properties than compound 1. TH-4 and TH-8 had a MIC of 12.5£¿¦ÌM and 25£¿¦ÌM for C. coli and 50£¿¦ÌM and 100£¿¦ÌM for C. jejuni, respectively. Cytological studies revealed that both compounds affected C. jejuni envelope integrity. Further, both compounds had no effect on other foodborne pathogens. TH-4 and TH-8 had a minimal impact on the chicken cecal microbiota and were not toxic to colon epithelial cells and chicken macrophages, and red blood cells at 200£¿¦ÌM. Further, TH-4 and TH-8 reduced the Campylobacter load in chicken ceca (up to 2-log reduction) when infected chickens were orally treated for 5 days with 0.254£¿mg£¿kg£¿1; as well as against internalized Campylobacter in Caco-2 cells at 12.5£¿¦ÌM and higher. Our study identified two novel specific and safe benzyl thiophene sulfonamide derivatives having potential for control of Campylobacter in chickens and humans
%U https://www.nature.com/articles/s41429-019-0168-x