Infection susceptibility and alternative approaches to combating drug-resistant infections

Abstract

Despite significant advances in medical care, infectious diseases continue to be a leading cause of death worldwide. It is estimated that infectious diseases account for a quarter of reported deaths annually. The majority of severe infections are caused by frequently encountered microbes, rather than highly virulent pathogens, and generally affect individuals with compromised health status. Beyond instances of comorbidities exacerbating susceptibility, host determinants are major contributing factors to infection outcomes. While the development of antibiotics has revolutionized therapeutic treatments of infections, the overuse and misuse of antibiotics has resulted in an alarming rise in antimicrobial-resistant infections. The rise in antimicrobial resistance intensifies the burden to human health and creates significant increases in health care costs. Thus, a greater understanding of genetic predisposition and host factors governing innate and adaptive immunity would facilitate the development of effective preventative measures and therapies aimed at enhancing immune defenses. The work presented here fills critical gaps in knowledge by identifying Cpt1a as a host determinant for infection outcome, describes alternative therapeutic applications for aminoglycoside antibiotics, and initiates a rigorous investigation into the utility of the HLA class I Supertype hypothesis in T cell targeted vaccine development.