Dr. Mahan’s research is focused on the molecular mechanisms underlying bacterial pathogenesis and developing practical solutions to combat infectious agents. He co-developed In Vivo Expression Technology (IVET), a genetic tool for discovering bacterial genes expressed during infection. His laboratory discovered an essential role for DNA adenine methylation (Dam) in bacterial virulence. Dam-deficient mutants aberrantly express multiple bacterial antigens, enabling the development of novel live vaccines. They also co-discovered a general mechanism of secreted glycoprotein aging and turnover that modulates sepsis pathogenesis and disease outcome. This host-protective mechanism is disrupted by Gram-negative pathogens that accelerate aging and clearance of host anti-inflammatory enzymes that drive LPS detoxification, thereby increasing inflammation and mortality. Additionally, recurrent subtherapeutic Salmonella infections led to the development of colitis, potentially linking food poisoning to intestinal bowel disease via reduced LPS detoxification in the gut. In response to the COVID-19 pandemic, Mahan’s laboratory developed a smartphone-based pathogen detection system that brings state-of-the-art diagnostics within reach of smartphone users. To address the escalating threat of antibiotic resistance, they developed a novel antimicrobial susceptibility test that identified several effective antibiotics rejected by standard testing, and may improve the way antibiotics are developed, tested, and prescribed. Further, they identified a broad-spectrum antibiotic (conjugated oligoelectrolyte) that cured otherwise untreatable infections and is being developed as a new versatile therapy for multi-drug resistant infections.