Rachna Chinya

Antibiotic treatment is vital to modern medicine, but its efficacy is impaired in immunocompromised hosts, even when pathogens are sensitive to antibiotics. We hypothesized that a synergy between antibiotic therapy and the host’s immune system drives infection clearance, and this synergy is lost in immunocompromised patients, reducing antibiotic effectiveness. We evaluated our hypothesis in a wound model of Pseudomonas aeruginosa infection using C57B/L6 immunocompetent and NSG immunodeficient mice with or without systemic Tobramycin. Bioavailable lipopolysaccharide (LPS) was assessed using HEK-Blue TLR4 reporter cells and pro-inflammatory cytokine levels (IL-1β and TNF-α) were quantified through RT-PCR, ELISA and Western Blotting. Our data indicate that Tobramycin treatment significantly increased bioavailable lipopolysaccharide triggering Toll-like receptor signaling and pro-inflammatory cytokine production that facilitated bacterial clearance. Conversely, Tobramycin-treated NSG mice showed no elevation in bioavailable LPS or cytokine levels and remained susceptible to infection. This demonstrates the importance of immune system-antibiotic synergy in controlling infection.