Description:
Available for licensing and commercial development are compositions and methods for the treatment and inhibition of Methicillin-resistant
Staphylococcus aureus (MRSA), a dangerous human pathogen. The invention concerns immunogenic peptides that can be used to induce protective immunity against MRSA, including phenol-soluble modulin (PSM) peptides.
In addition to the MRSA infections that occur in immunocompromised patients in hospitals, new MRSA strains have recently emerged that can cause severe infections (such as necrotizing fasciitis) or death in otherwise healthy adults. These strains are increasingly involved in community-associated (CA)-MRSA infections, and can be contracted outside of the health care settings. The incidence of CA-MRSA infections is increasing and the majority of infections in patients reporting to emergency departments in the US is now due to CA-MRSA.
The invention describes a class of secreted staphylococcal peptides with an extraordinary ability to recruit, activate, and subsequently lyse human neutrophils, thus eliminating the main cellular defense against
S. aureus infection. The peptides are encoded by the PSM gene cluster and include PSMalpha1, PSMalpha2, PSMalpha3, and PSMalpha4, all of which activate and subsequently lyse neutrophils. These peptides are produced at especially high levels in CA-MRSA and to a large extent determine their aggressive behavior and ability to cause disease in animal models of infection. Thus, the peptides represent a set of virulence factors of
S. aureus that account for the enhanced virulence of CA-MRSA. The identification of these peptides enables the production of vaccines and other preventative and/or therapeutic agents for use in subjects infected with MRSA.