Babesiosis: An Emerging Infectious Threat to Transfusion Medicine

Summary

Principal Investigator: Cheryl Ann Lobo
Abstract: DESCRIPTION (provided by applicant): Babesiosis is a zoonosis, a disease communicable from animals to man. The rodent parasite, Babesia microti and the bovine pathogen, Babesia divergens are responsible for most of the human infections that have been reported to date, globally. From a blood safety perspective, transfusion-transmitted infections involving Babesia spp. have become increasingly problematic in the USA, with progressively more reported each year. Therefore the study of this blood-borne parasite should be considered as a priority for transfusion medicine. Our purpose is to understand the invasion process of B. divergens into the human red blood cell (RBC), with the ultimate aim of exploiting parasite molecules found to play key roles in invasion as diagnostic and blood screening tools. The in-vitro system that we use for studying invasion of the human red cell by B. divergens, permits direct exploration of the events associated with parasite invasion of the human RBC, using viable merozoites of B. divergens. Molecules on the surface of the parasite and those secreted by apical organelles function at the host/parasite interface, and we need to identify them and determine their interactions and function, if we are to define the steps in the invasion mechanism and identify new therapeutic targets. We have identified one such putative RBC binding ligand, Bd30 and the focus of our project is the study of its interaction with the RBC, specifically the glycophorins, during parasite invasion. There are three specific aims in this proposal (1) To characterize glycophorin A (GPA) and glycophorin B (GPB) as RBC receptors for B. divergens invasion (2) To validate Bd30 as the B. divergens ligand that binds glycophorin A (GPA) and/or glycophorin B (GPB) and to characterize Bd30 in the parasite and (3) To evaluate the functional significance of the interaction between GPA and/or GPB and Bd17 in merozoite invasion. Methodology that is proposed includes inhibition of invasion assays using specific enzyme treatments of the RBC, mutant cells lacking defined RBC antigens and the use of antibodies and competitor peptides;erythrocyte binding assays using native and recombinant Bd30 ligand protein and antibodies against Bd30 in invasion assays, as well as proposed gene deletion to study its function. Thus, the major goal of the project is to elucidate the molecular mechanisms involved in the entry of B. divergens merozoites into the erythrocyte. It is anticipated that studies detailed in this proposal will result in reagents for diagnosis, epidemiology and treatment and prevention of human babesiosis, and assist in developing products to screen blood products. PUBLIC HEALTH RELEVANCE: Babesiosis is a zoonosis, a disease communicable from animals to man and an important blood-borne human parasitic infection. Human to human transmission of the parasite is well recognized to occur through blood transfusion. Despite being a significant threat to the safety of blood transfusions, its study has largely been neglected. The long term objective of the present proposal is to develop a detailed mechanistic understanding of the erythrocytic invasion of the B. divergens parasite in order to develop novel therapies for treating the infection and effective strategies for screening of blood donors for babesia infection. We are specifically looking at interactions between the RBC receptors, glycophorins A and B and the Babesia molecules that bind to them so that we can define the steps in the invasion mechanism. Recognizing that Babesia is an expanding blood safety threat we are interested in the development of viable interventions to detect and halt transmission of these pathogens via blood transfusions.
Funding Period: 2011-04-01 - 2016-03-31
more information: NIH RePORT

Top Publications

  1. ncbi Babesia and red cell invasion
    Cheryl A Lobo
    Laboratory of Blood Borne Parasites, Lindsley Kimball Research Institute, New York Blood Center, New York 10021, USA
    Curr Opin Hematol 19:170-5. 2012
  2. pmc Babesia: impact of cold storage on the survival and the viability of parasites in blood bags
    Jeny R Cursino-Santos
    Department of Blood Borne Parasites, Lindsley Kimball Research Institute, New York Blood Center, New York, New York
    Transfusion 54:585-91. 2014
  3. pmc Identification of binding domains on red blood cell glycophorins for Babesia divergens
    Jeny R Cursino-Santos
    Department of Blood Borne Parasites, Lindsley Kimball Research Institute, New York Blood Center, New York, New York
    Transfusion 54:982-9. 2014

Detail Information

Publications4

  1. ncbi Babesia and red cell invasion
    Cheryl A Lobo
    Laboratory of Blood Borne Parasites, Lindsley Kimball Research Institute, New York Blood Center, New York 10021, USA
    Curr Opin Hematol 19:170-5. 2012
    ..The objective of this review is to present up-to-date information on both parasite and red blood cell molecules that function at the host-parasite interface to facilitate successful invasion...
  2. pmc Babesia: impact of cold storage on the survival and the viability of parasites in blood bags
    Jeny R Cursino-Santos
    Department of Blood Borne Parasites, Lindsley Kimball Research Institute, New York Blood Center, New York, New York
    Transfusion 54:585-91. 2014
    ..It is important to understand the effect of blood storage conditions on the viability of Babesia as this will impact the occurrence and severity of transfusion-transmitted babesiosis...
  3. pmc Identification of binding domains on red blood cell glycophorins for Babesia divergens
    Jeny R Cursino-Santos
    Department of Blood Borne Parasites, Lindsley Kimball Research Institute, New York Blood Center, New York, New York
    Transfusion 54:982-9. 2014
    ..Earlier work has shown that GPA and GPB function as putative receptors during parasite invasion. The primary focus of this study was the delineation of parasite-binding domains on GPA and GPB...

Research Grants30

  1. Mechanisms of mosquito midgut invasion by Plasmodium ookinetes
    Marcelo Jacobs-Lorena; Fiscal Year: 2013
    ..Knowledge generated by these studies may have important implications for the development of multivalent transmission-blocking vaccines. ..
  2. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
    ..Through all of its activities, the Center improves communication, promotes collaboration, develops careers and generally enriches the intellectual climate for digestive disease research. ..
  3. New infection-related proteins of Plasmodium sporozoites and liver stages
    Stefan H I Kappe; Fiscal Year: 2013
    ..Identifying major liver stage-host hepatocyte interactions and elucidating their functional significance will reveal fundamental principles of malaria parasite liver infection and provide new avenues for preventive drug design. ..
  4. Expanding the National Health Accounts
    David M Cutler; Fiscal Year: 2013
    ..Establishment of a set of national health accounts will allow us as a society to understand which medical interventions improve the health of the U.S. population most efficiently. ..
  5. A prospective evaluation of chronic B.microti infection in seroreactive blood don
    EVAN MARTIN BLOCH; Fiscal Year: 2013
    ..PCR) and policy of deferral and reinstatement. We intend to use the sample repository for a future submission to determine the genetic and immunologic determinants of chronic vs. transient infection. ..