Role of novel peptide, EP67, in controlling bacterial infection

Includes bibliographical references (p. 40-47).Infectious diseases have re-emerged as one of the greatest global health challenges of the 21st century. However, the treatments available to control infections have demonstrated a remarkable deficiency in their ability to fight numerous bacterial pathogens that cause disease. Therefore, novel strategies and treatments must be examined to tackle this growing challenge. One approach currently under investigation is the employment of host immune defenses, more specifically those involved in innate immunity. The innate immune system serves as the body's first line of defense during a pathogenic microbial assault. A variety of cell populations including neutrophils, macrophages and dendritic cells are involved in innate immune function, releasing diverse mediators such as alarmins, cytokines and chemokines. Among the compounds capable of activating the cells involved in innate immunity is the complement fragment, C5a. The principal role of native C5a is to recruit inflammatory cells and lymphocytes to sites of tissue injury and infection, and to then activate various effector responses including neutrophil degranulation, and inflammatory and chemotactic mediator release. Toward this end our collaborators have developed a unique innate immune activator known as EP67, derived from the biologically active region of human C5a. EP67 induces the activation of macrophages and dendritic cells resulting in the synthesis and release of multiple cytokines important for the activation of innate immunity. We have also observed that EP67 exhibits antimicrobial properties. Currently, we are investigating the use of EP67 as a novel immunobiotic to fight infectious diseases caused by two significant Gram-positive human pathogens, antibiotic resistant Staphylococcus aureus (MRSA) and Streptococcus agalactiae (group B streptococcus, GBS)