Opportunistic Parasites of Immunocompromised Individuals

Cryptosporidium parvum belongs to a ubiquitous and diverse group of intracellular apicomplexans of both human and veterinary importance. C. parvum is an intracellular protozoan parasite causing enteric infection and severe diarrheal disease in various mammals, including humans. This parasite is now the most commonly reported etiologic agent isolated from diarrheic calves in the United States. Recently there have been large outbreaks of waterborne human cryptosporidiosis, such as the one in Milwaukee, Wisconsin, in which more than 400,000 people were affected. The importance of C. parvum as a human pathogen was first recognized among immunocompromised hosts, notably AIDS patients. In this population, the disease can become chronic and unremitting, and may be a direct cause of death. As a result of improved diagnostic methods and an increasing awareness of C. parvum as an agent of human disease, this parasite is now recognized as a common cause of diarrheal illness in both immunocompetent and immunocompromised humans.

Despite intensive research in recent years, there are no effective preventive measures or treatment regimens available for this disease. Due to the serious nature of C. parvum infection in immunocompromised patients and the risk of infection from drinking water we have in collaboration with Dr. Rizzo’s group at Pace University developed an antimicrobial matrix for commercial water filters to reduce the incidence of disease.

Our studies have demonstrated that C. parvum utilizes a unique pathway for the biosynthesis of polyamines, involving arginine decarboxylase (ADC) coupled to a reverse polyamine biosynthetic pathway, mediated by spermidine: spermine N1-acetyltransferase (SSAT) and polyamine oxidase (PAO), which is 10-fold more active than the forward pathway. These differences in polyamine synthesis present a unique target for chemotherapeutic intervention.

Student projects include: in vitro testing of new compounds for ability to block parasite invasion of host cells; study of highly active compounds in an in vivo mouse model assay; the examination of possible mechanism(s) of action of active compounds within polyamine metabolism in C. parvum; the effect of C. parvum on host cell apoptosis.