A call-back for colistin: Screening for adjuvants of a last-resort antibiotic against invasive non-typhoidal Salmonella

Invasive non-typhoidal Salmonella (iNTS) has evolved beyond its gut-restricted lifestyle to cause bloodstream infections in immunocompromised populations, particularly in sub-Saharan Africa. A major concern is the lack of treatment options available for iNTS infections, which are typically multidrug-resistant, preventing the use of first-choice antibiotics to clear the bacteria. In such cases, clinicians might need to administer last-resort antibiotics, which often have toxic side effects at the recommended therapeutic dose. I will conduct a high-throughput compound screen in infection-relevant conditions to identify a chemical adjuvant to an otherwise effective last-resort antibiotic. Our main aim is to dose-spare either drug in a combination treatment and ultimately, mitigate toxicity. We propose that using infection-relevant conditions to mimic the bacterial growth environment within an infected host will reveal more weak spots in iNTS that would remain hidden using traditional screening approaches. Overall, this work supports the development of a safe and effective treatment for individuals infected with multidrug-resistant iNTS, thus addressing an unmet clinical need.