Abstract
The control of Salmonella from farm to fork is challenging due to the emergence of antimicrobial-resistant isolates and the limited effects of current control methods. Advanced chemical technologies have made accessible a wide range of uncharacterized small molecules (SMs) with encouraging chemical properties for antimicrobial treatment. Of the 4,182 SMs screened in vitro, four cidal SMs were effective at 10 µM and higher against several serotypes, antibiotic-resistant, and biofilm embedded Salmonella enterica subsp. enterica serotype Typhimurium by altering cell membrane integrity. The four SMs displayed synergistic effects with ciprofloxacin, meropenem and cefeprime against Salmonella. Further, the SMs were not pernicious to most eukaryotic cells at 200 μM and cleared internalized Salmonella in infected Caco-2, HD11, and THP-1 cells at 6.25 µM and higher. The SMs also increased the longevity of Salmonella-infected Galleria mellonella larvae and reduced the population of internalized Salmonella Typhimurium. Two of the SMs (SM4 and SM5) also reduced S. Typhimurium load in infected chicken ceca as well as its systemic translocation into other tissues, with minimal impact on the cecal microbiota. This study demonstrated that SMs are a viable source of potential antimicrobials applicable in food animal production against Salmonella.
Highlights
The control of Salmonella from farm to fork is challenging due to the emergence of antimicrobialresistant isolates and the limited effects of current control methods
This study demonstrated that small molecules (SMs) are a viable source of potential antimicrobials applicable in food animal production against Salmonella
Typhimurium growth between 20% to 100% when Salmonella was grown in minimal nutrient conditions (M9 medium) for 12 hrs
Summary
The control of Salmonella from farm to fork is challenging due to the emergence of antimicrobialresistant isolates and the limited effects of current control methods. Pharmaceutical companies have developed thousands of new generation small molecules (SMs) Some of these SMs have been shown to be effective against multi-drug resistant pathogens such as Staphylococcus, Burkholderia, Pseudomonas, and Candida, where conventional antibiotics failed[15,16,17,18]. After screening a library of 4,182 SMs, our study identified two novel potent SMs effective at low concentration against various serotypes, antibiotic-resistant, and biofilm embedded Salmonella These SMs possessed low toxicity to eukaryotic cells and were effective in reducing Salmonella in Galleria mellonella wax moth larvae and in chickens with minimal impact on the chicken cecal microbiota. Cytological profiling revealed that these SMs function by altering Salmonella cell membrane integrity
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