Methicillin Resistant Staphylococcus aureus (MRSA) is a drug-resistant form of bacteria first recognized in the 1960s. For many years, it was limited mainly to hospitalized patients, those in contact with such patients and injection drug users. In recent years a different form called community-acquired MRSA has spread outside the hospital to the general population. A highly invasive type of infection by community-acquired MRSA can cause significant morbidity and mortality in otherwise healthy children and adults.

Infectious disease research has long focused on the pathogen’s role in infection, but less so on how the individual host genome iinfluences resistance or susceptibility to infection. The current epidemic of MRSA infection provides an opportunity to apply new genetic methods to understand this disease by focusing on both pathogen genomics as well as the genes involved in the host response to infection.

MRSA. Credit: CDC/Janice Carr.

There are multiple outcomes from MRSA infection, ranging from curable localized infection to devastating invasive infection. Some patients have a single episode of skin or soft tissue infection, while a minority present with invasive, life-threatening infections such as sepsis, necrotizing pneumonia and deep muscle or bone abscesses. This project aims to understand how the host and pathogen genotypes determine which type of infection occurs.

The project is applying high-throughput DNA sequencing of candidate genes involved in immune and other host responses to infection to discover what mutations and genes are involved. The project is also sequencing MRSA samples from patients to determine if there are changes in the bacterial genome that contribute to the severity of the infection.

The hope is that this information will eventually allow rapid prediction of the type of infection occuring. The ability to recognize how a disease will progress at such an early stage of infection will allow for more rapid, informed treatment and personalized therapy based on the genomes of both the pathogen and the individual, improving chances of survival before the invasive bacterial load becomes overwhelming. Using such current innovations in genetic analysis will lead to a broad improvement in many areas of infectious disease and public health.