Backpackers Beware! Human Protozoan Parasitic Diseases
Tuesday, November 30, 2010
Presented by the Emerging Infectious Diseases & Microbiology Discussion Group
Between backpacking and high-density city living, a plethora of protozoan and fungal parasites abound that are easily transmitted to humans through food and water, from domestic pets, cattle, via sexual contact or in aerosols. Such parasites may lie dormant, or can cause debilitating illness, particularly in immunocompromised individuals. Humans may be protected from such parasites due to innate immunity, but some parasitic species are showing resistance, infecting humans and causing serious illness. This symposium provides an update on research into some of these diseases, including sleeping sickness, malaria and Cryptosporidium, covering pathogenicity, transmission and treatment.
*Presentation times are subject to change.
Sweet and Sticky: The Role of Carbohydrates in Cryptosporidium - Host Cell Interactions
Tsetse flies and trypanosomes versus bovines, baboons and backpackers
P. falciparum versus the human host: Is there an arms race?
Shirley Raps, PhD
Hunter College, CUNY
Shirley Raps, Professor and Chair of the Department of Biological Sciences at Hunter College of CUNY, is a long-time member of the Microbiology Section of the NYAS. Her research has involved characterizing Microcystis aeruginosa strain UV027, a fresh water, toxin-producing cyanobacterium known to be a health hazard to animals and humans. She has analyzed the light harvesting complex, the phycobilisome, of this bacterium, sequenced the two operons involved in the non-ribosomal synthesis of the heptapeptide toxin microcystin RR in strain UV027, and is examining ways to control the expression of this toxin. She isolated the sole plasmid from UV027, ligated it to pBluescript and created a shuttle vector as a potential transformation system. Her lab is also well on its way towards completely sequencing the genome of this organism.
Dr. Raps is also involved in science education with funding from an HHMI Undergraduate Science Education Grant. The grant funds the promotion of research by undergraduates at Hunter College, at the Marine Biological laboratory and the Cold Spring Harbor Laboratories, in order to encourage these students to pursue research careers via PhD or MD-PhD programs. She is also Director of an Outreach Program to high school and middle school teachers and their students with the goal of increasing the interest in science/scientific research among pre-college students. She is partnering with the Manhattan Hunter Science High School to enable interested students to take a Research Techniques Facility Workshop during the academic year and participate in a summer research internship at Hunter College.
Jennifer Henry. PhD
The New York Academy of Sciences
Johanna Daily, MD
Albert Einstein College of Medicine
Dr. Daily is an Infectious Disease trained physician who has been carrying out field studies of malaria for over ten years. She received her MD at SUNY Upstate, completed an Internal Medicine residency at Tufts Medical Center and an Infectious Disease fellowship at the Brigham and Women’s Hospital. She is presently an associate professor in the departments of Medicine (Infectious Disease) and Microbiology and Immunology at Albert Einstein College of Medicine. Her laboratory research interest is in the epidemiology and pathogenesis of the malaria parasite Plasmodium falciparum. The goal of the research has been to define the molecular mechanisms that underlie the variation of disease outcomes in P. falciparum. They have identified novel parasite biology when it resides in the human host; this biology has not been reported under in vitro cultivation and may play a role in enhanced virulence and/or transmission capacity. To further understand the implications of these novel in vivo states they study the parasite under in vitro conditions that mimic host blood stream conditions. They are also studying host response to infection using whole genome approaches to identify host factors that associate with severe disease outcomes. Using a complementary approach of high throughput small molecule analysis they have begun to identify parasite specific small molecules in vivo and in vitro. The long term goal is to refine the model of pathogenesis to identify parasite and host processes involved in disease to serve as targets for vaccine or chemotherapeutic development.
Jayne Raper, PhD
New York University School of Medicine
Jayne Raper has been working on African Trypanosomiasis for 25 years. Starting in the UK, then working in Brazil, Belgium and Kenya. She is currently an Associate Professor at New York University School of Medicine in the department of Microbiology and Parasitology. Her research interests have always been in host parasite interactions. Recently she has begun to investigate the broader microbicidal action of TLF, the good cholesterol, against other parasites and bacteria.
Honorine Ward, MD
Tufts University School of Medicine
Honorine Ward, MD is Professor of Medicine at Tufts University School of Medicine and directs an NIH-funded research and training program on HIV/AIDS and associated opportunistic infections at Tufts Medical Center. She is program director of the HIV pathogenesis training program for MD and PhD post-doctoral fellows at Tufts medical Center. Her laboratory studies the apicomplexan parasite Cryptosporidium which is a significant cause of diarrheal disease worldwide, particularly in patients with HIV/AIDS and malnourished children in developing countries. Her research is focused on investigating the role of parasite and host glycoproteins and glycan binding proteins in mediating parasite attachment to and invasion of host intestinal epithelial cells. In addition she is investigating enzymes such as subtilases and glycosyl transferases that postranslationally modify these proteins and which may serve as targets for intervention. In clinical and translational studies, she is studying the molecular epidemiology of cryptosporidiosis and investigating immune responses to proteins that mediate attachment and invasion, in infected children and HIV-infected adults in developing countries. New areas of research are directed at investigating alterations in the intestinal microbiota in cryptosporidiosis and the use and mechanism of action of probiotics for treatment of cryptosporidiosis in children. The long term goal of her studies is to develop specific, preventive and therapeutic interventions for cryptosporidiosis.
P. falciparum versus the human host: is there an arms race?
Johanna Daily, MD, Albert Einstein College of Medicine
Infection with the malaria parasite Plasmodium falciparum leads to widely different clinical conditions in the human host – ranging from asymptomatic, to mild flu-like symptoms to coma and death. Despite the immense medical implications, the genetic and molecular basis of this diversity remains largely unknown. We hypothesize that parasites alter their biology based on host cues and this may contribute to variation in disease states. Our data suggests that some hosts chose a highly inflammatory response to infection; the parasite in turn responds to inflammation with a change in biology, possibly resulting in a more virulent state. This dynamic interaction is reminiscent of an arms race and may be ultimately detrimental to the host. We utilize whole genome analysis of the parasite directly from blood samples of infected patients to characterize parasite biology in a comprehensive manner. We identified previously unknown physiological diversity in the in vivo biology of the malaria parasite, not seen under standard laboratory in vitro cultivation methods. We now will present data derived from a cohort of children with severe disease and identify parasite biology associated with severe disease and mortality. In addition we have begun to analyze the host environment with human transcription profiling to begin to understand the components of host response that alter parasite biology. The long term goal is to identify parasite or host biology that can be targeted to reduce individual and global health burden of Plasmodium falciparum.
Tsetse flies and trypanosomes versus bovines, baboons and backpackers
Jayne Raper, PhD, New York University School of Medicine
Bovine African Trypanosomiasis is prevalent in 36 countries of sub-Saharan Africa. It is caused by Trypanosoma congolense, T. vivax, and T. brucei brucei and is transmitted by the tsetse ﬂy. Humans are protected from these parasites due to an innate immune complex called trypanosome lytic factor (TLF), a subtype of high-density lipoprotein (the good cholesterol). TLF is a primate specific immune factor ONLY found in humans, some Great Apes and Old World Monkeys. Within the lipid/protein complex apolipoprotein L-I is the component that is necessary for the lethal action of TLF. Two other trypanosome species, T. b. rhodesiense and T. b. gambiense, are resistant to human TLF and therefore infect humans and cause sleeping sickness, known as Human African Trypanosomiasis (HAT). Cattle are also infected by T. b. rhodesiense and due to their close proximity with humans act as reservoirs that facilitate the transmission of HAT. Some Old World Monkeys including baboons are naturally resistant to all African trypanosomes. We have recently isolated the baboon APOL1 orthologue, which is 60% similar to human APOL1. Transgenic mice with this gene are protected against human infective and the cattle pathogens. Due to this discovery we are developing transgenic cattle that carry baboon APOL1 and will evaluate their ability to resist infection. We can also use the baboon apoL-I protein therapeutically to cure backpackers who get bitten by infected tsetse flies.
Sweet and Sticky: The Role of Carbohydrates in Cryptosporidium-Host Cell Interactions
Honorine Ward, MD, Tufts University School of Medicine
The apicomplexan parasite Cryptosporidium is a significant cause of gastrointestinal disease worldwide, particularly in immunocompromised hosts such as patients with HIV/AIDS and malnourished children in developing countries. Treatment options for cryptosporidiosis are limited and there is no vaccine available. Unlike other apicomplexan parasites, Cryptosporidium utilizes mucin-like glycoproteins such as gp900 and gp40 present on the surface of invasive stages of the parasite to attach to host cells. Lectins and a monoclonal antibody (mAb) 4E9, specific for core Tn and T antigens GalNAcα1-Ser/Thr and Galβ1-3GalNAcα1-Ser/Thr present on gp40 and gp900 block Cryptosporidium infection in vitro and in vivo indicating that these carbohydrate residues are important for infection. Currently, our goal is to identify the 4E9 epitope on gp40 and gp900 and the UDP-N-acetyl-D-galactosamine:polypeptide N-acetyl galactosaminyltransferase(s) (ppGalNAcT(s) that catalyze its synthesis. The long term goal is to determine if this epitope and the ppGalNAcT/s that synthesize it can be targeted for prevention or intervention of cryptosporidiosis.
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