Nitrate potentiates kanamycin activity in bacteria through metabolic reprogramming and CpxR-associated respiratory activation.

Nitrate enhances kanamycin activity in Salmonella enterica serovar Enteritidis by increasing bacterial bioenergetics and drug accumulation, even in resistant strains.

• Why it matters: Antibiotic resistance in foodborne bacteria threatens public health and livestock production, highlighting the need for strategies that improve existing antibiotic efficacy without relying solely on genetic resistance reversal.
• What they did: The study used comparative proteomic profiling and infection models to show that nitrate boosts NADH production, TCA cycle activity, and proton motive force, while also altering CpxR-regulated respiratory genes, supporting a metabolic adjuvant approach.
• The result: Nitrate potentiated kanamycin killing in both resistant and susceptible strains and improved treatment outcomes in animal infection models, suggesting inorganic nitrogen metabolism as a target for adjuvant development.