David R Allred

David R Allred,

Professor

Department: Department of Infectious Diseases & Immunology
Business Phone: (352) 294-4126
Business Email: allredd@ufl.edu

Accomplishments

Editorial Board
2008 · Eukaryotic Cell
Editorial Board
2007 · The Open Parasitology Journal
Editorial Board
2007 · Molecular and Biochemical Parasitology
Faculty Research Productivity Award
1999 · University of Florida
Outstanding Faculty Achievement and Performance Award
1995 · University of Florida
C.E. Cornelius Young Investigator Faculty Research Award
1990 · University of Florida

Research Profile

Mechanisms of persistence in babesial parasites

The long-term goal of the Allred Laboratory is to find the means to protect animals and humans from the pathology of parasitic infection. The approach we have taken is to identify mechanisms used by blood-borne parasites to interact with their vertebrate hosts in order to establish and maintain persistent infections. Our current primary focus is on mechanisms used by babesial parasites to survive and establish highly persistent infections in hosts that are immune to disease. We have chosen to make the bovine pathogen, Babesia bovis, our primary study target, in part because it shares many biological parallels with the human malarial parasite, Plasmodium falciparum.

B. bovis is a bovine parasite that causes a devastating acute disease but which goes on to establish a generally asymptomatic persistent infection lasting many years. During the persistent infection, the surface of IRBCs becomes altered antigenically during parasite development, and B. bovis-infected red blood cells (IRBCs) carrying mature parasites sequester in the vasculature of the deep organs, sometimes leading to highly lethal cerebral babesiosis. We are investigating the bases for these linked behaviors. In the process, we have demonstrated these changes are due, at least in part, to the expression of parasite-derived proteins, particularly VESA1, on the IRBC membrane surface. VESA1 mediates cytoadhesion, allowing mature IRBCs to sequester in the deep organs. We have shown the sensitivity of cytoadhesion to the presence of antibodies recognizing VESA1, opening up the possibility of immunizing animals to protect from the pathology of this disease. However, this is complicated by the fact that VESA1 also undergoes rapid antigenic variation during the course of infection in an individual animal, rendering pre-existing antibodies ineffective. Our studies on the molecular genetic basis for antigenic variation in B. bovis have resulted in the identification and characterization of the ves multigene family encoding VESA1 subunits. We have determined that B. bovis employs “segmental gene conversion” to construct mosaic ves genes from bits of many ves genes, and are currently identifying the enzymatic machinery mediating this. The variability in antigenicity and function that can be generated in this way is staggering, and helps to explain how this parasite successfully evades ongoing antibody responses targeting the IRBC.

Ongoing projects

We are currently studying the molecular basis for regulation of ves gene expression, as well as the enzymatic machinery required for gene conversion events in antigenic variation. Moreover, we are collaborating on detection of the mechanisms enabling intracellular parasites to export proteins such as VESA1 and Smorf out into the infected host cell. We are also collaborating on a related project with the bacterial pathogen, Anaplasma phagocytophilum. Currently, we are studying the enzymatic machinery responsible for DNA repair, including segmental gene conversion, to identify logical targets for their lethal disruption. In a parallel approach, we have been involved in non-targeted drug studies to identify novel drugs that might be used to treat babesial infections, and have found candidates for further exploration. We look forward to the implementation of one or more of these approaches in the future.

Open Researcher and Contributor ID (ORCID)

0000-0001-9347-5918

Publications

2020
A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity
PLOS Pathogens. 16(5) [DOI] 10.1371/journal.ppat.1008600. [PMID] 32453775.
2020
Babesia bovis Rad51 ortholog influences switching of ves genes but is not essential for segmental gene conversion in antigenic variation
PLOS Pathogens. 16(8) [DOI] 10.1371/journal.ppat.1008772. [PMID] 32866214.
2020
Disruption of VirB6 Paralogs in Anaplasma phagocytophilum Attenuates Its Growth.
Journal of bacteriology. 202(23) [DOI] 10.1128/JB.00301-20. [PMID] 32928930.
2019
Inaugural meeting of the international babesiosis research community, 2018: A glimpse into the future of an emerging research field.
International journal for parasitology. 49(2):93-94 [DOI] 10.1016/j.ijpara.2019.02.001. [PMID] 30827459.
2019
Knockout of Babesia bovis rad51 ortholog and its complementation by expression from the BbACc3 artificial chromosome platform
PLOS ONE. 14(8) [DOI] 10.1371/journal.pone.0215882. [PMID] 31386669.
2019
Up-regulated expression of spherical body protein 2 truncated copy 11 in Babesia bovis is associated with reduced cytoadhesion to vascular endothelial cells.
International journal for parasitology. 49(2):127-137 [DOI] 10.1016/j.ijpara.2018.05.015. [PMID] 30367864.
2019
Variable and Variant Protein Multigene Families in Babesia bovis Persistence
Pathogens. 8(2) [DOI] 10.3390/pathogens8020076. [PMID] 31212587.
2016
Extensive Shared Chemosensitivity between Malaria and Babesiosis Blood-Stage Parasites.
Antimicrobial agents and chemotherapy. 60(8):5059-63 [DOI] 10.1128/AAC.00928-16. [PMID] 27246780.
2015
Shared elements of host-targeting pathways among apicomplexan parasites of differing lifestyles.
Cellular microbiology. 17(11):1618-39 [DOI] 10.1111/cmi.12460. [PMID] 25996544.
2014
The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction.
Nucleic acids research. 42(11):7113-31 [DOI] 10.1093/nar/gku322. [PMID] 24799432.
2013
Unusual chromatin structure associated with monoparalogous transcription of the Babesia bovis ves multigene family.
International journal for parasitology. 43(2):163-72 [DOI] 10.1016/j.ijpara.2012.10.018. [PMID] 23178996.
2012
Characterization of the unusual bidirectional ves promoters driving VESA1 expression and associated with antigenic variation in Babesia bovis.
Eukaryotic cell. 11(3):260-9 [DOI] 10.1128/EC.05318-11. [PMID] 22286091.
2012
Outbreak of equine piroplasmosis in Florida.
Journal of the American Veterinary Medical Association. 240(5):588-95 [DOI] 10.2460/javma.240.5.588. [PMID] 22332629.
2010
The Babesia bovis VESA1 virulence factor subunit 1b is encoded by the 1beta branch of the ves multigene family.
Molecular and biochemical parasitology. 171(2):81-8 [DOI] 10.1016/j.molbiopara.2010.03.001. [PMID] 20226217.
2009
Universal primers suitable to assess population dynamics reveal apparent mutually exclusive transcription of the Babesia bovis ves1alpha gene.
Molecular and biochemical parasitology. 166(1):47-53 [DOI] 10.1016/j.molbiopara.2009.02.008. [PMID] 19428672.
2009
varDB: common ground for a shifting landscape.
Trends in parasitology. 25(6):249-52 [DOI] 10.1016/j.pt.2009.03.003. [PMID] 19423393.
2007
Dynamics of anemia progression and recovery in Babesia bigemina infection is unrelated to initiating parasite burden.
Veterinary parasitology. 146(1-2):170-4 [PMID] 17353098.
View on: PubMed
2006
Antigenic variation as an exploitable weakness of babesial parasites.
Veterinary parasitology. 138(1-2):50-60 [PMID] 16517078.
View on: PubMed
2006
Antigenic variation in Babesia bovis occurs through segmental gene conversion of the ves multigene family, within a bidirectional locus of active transcription.
Molecular microbiology. 59(2):402-14 [PMID] 16390438.
View on: PubMed
2006
Evaluation of cattle inoculated with Babesia bovis clones adhesive in vitro to bovine brain endothelial cells.
Annals of the New York Academy of Sciences. 1081:397-404 [PMID] 17135543.
View on: PubMed
2004
Antigenic variation and cytoadhesion in Babesia bovis and Plasmodium falciparum: different logics achieve the same goal.
Molecular and biochemical parasitology. 134(1):27-35 [PMID] 14747140.
View on: PubMed
2003
Babesiosis: persistence in the face of adversity.
Trends in parasitology. 19(2):51-5 [PMID] 12586467.
View on: PubMed
2001
Antigenic variation in babesiosis: is there more than one ‘why’?
Microbes and infection. 3(6):481-91 [PMID] 11377210.
View on: PubMed
2001
Molecular technology and antigenic variation among intraerythrocytic hemoparasites: do we see reality?
Veterinary parasitology. 101(3-4):261-74 [PMID] 11707301.
View on: PubMed
2000
Selection of Babesia bovis-infected erythrocytes for adhesion to endothelial cells coselects for altered variant erythrocyte surface antigen isoforms.
Journal of immunology (Baltimore, Md. : 1950). 164(4):2037-45 [PMID] 10657656.
View on: PubMed
2000
The ves multigene family of B. bovis encodes components of rapid antigenic variation at the infected erythrocyte surface.
Molecular cell. 5(1):153-62 [PMID] 10678177.
View on: PubMed
1999
Cytoadherence of Babesia bovis-infected erythrocytes to bovine brain capillary endothelial cells provides an in vitro model for sequestration.
Infection and immunity. 67(8):3921-8 [PMID] 10417157.
View on: PubMed
1999
Selection and recovery of minor parasite populations expressing unique infected-erythrocyte phenotypes.
Molecular and biochemical parasitology. 100(1):125-9 [PMID] 10377000.
View on: PubMed
1998
Antigenic variation in Babesia bovis: how similar is it to that in Plasmodium falciparum?
Annals of tropical medicine and parasitology. 92(4):461-72 [PMID] 9683897.
View on: PubMed
1997
Characterization of a variant erythrocyte surface antigen (VESA1) expressed by Babesia bovis during antigenic variation.
Molecular and biochemical parasitology. 89(2):259-70 [PMID] 9364970.
View on: PubMed
1997
Immunochemical methods for identification of Babesia bovis antigens expressed on the erythrocyte surface.
Methods (San Diego, Calif.). 13(2):177-89 [PMID] 9405201.
View on: PubMed
1995
Babesia bigemina: host factors affecting the invasion of erythrocytes.
Experimental parasitology. 80(1):76-84 [PMID] 7821413.
View on: PubMed
1995
Immune evasion by Babesia bovis and Plasmodium falciparum: cliff-dwellers of the parasite world.
Parasitology today (Personal ed.). 11(3):100-5 [PMID] 15275361.
View on: PubMed
1994
Antigenic variation of parasite-derived antigens on the surface of Babesia bovis-infected erythrocytes.
Infection and immunity. 62(1):91-8 [PMID] 8262654.
View on: PubMed
1994
Characterization of hemagglutinating components on the Anaplasma marginale initial body surface and identification of possible adhesins.
Infection and immunity. 62(10):4587-93 [PMID] 7927725.
View on: PubMed
1994
Putative adhesins of Anaplasma marginale: major surface polypeptides 1a and 1b.
Infection and immunity. 62(10):4594-601 [PMID] 7927726.
View on: PubMed
1993
A nonsubjective assay for antigenic modifications of the Babesia bovis-parasitized erythrocyte surface.
The Journal of parasitology. 79(2):274-7 [PMID] 8459338.
View on: PubMed
1993
Isolate-specific parasite antigens of the Babesia bovis-infected erythrocyte surface.
Molecular and biochemical parasitology. 60(1):121-32 [PMID] 8366886.
View on: PubMed
1992
Polypeptides reactive with antibodies eluted from the surface of Babesia bovis-infected erythrocytes.
Memorias do Instituto Oswaldo Cruz. 87 Suppl 3:21-6 [PMID] 1343693.
View on: PubMed
1991
The msp1 beta multigene family of Anaplasma marginale: nucleotide sequence analysis of an expressed copy.
Infection and immunity. 59(3):971-6 [PMID] 1671779.
View on: PubMed
1990
Molecular basis for surface antigen size polymorphisms and conservation of a neutralization-sensitive epitope in Anaplasma marginale.
Proceedings of the National Academy of Sciences of the United States of America. 87(8):3220-4 [PMID] 1691504.
View on: PubMed
1989
Detection and quantitation of Anaplasma marginale in carrier cattle by using a nucleic acid probe.
Journal of clinical microbiology. 27(2):279-84 [PMID] 2915021.
View on: PubMed
1986
Dynamic rearrangements of erythrocyte membrane internal architecture induced by infection with Plasmodium falciparum.
Journal of cell science. 81:1-16 [PMID] 3525580.
View on: PubMed
1983
Developmental modulation of protein synthetic patterns by the human malarial parasite Plasmodium falciparum.
Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire. 61(12):1304-14 [PMID] 6367909.
View on: PubMed
1983
Increased fluidity of Plasmodium berghei-infected mouse red blood cell membranes detected by electron spin resonance spectroscopy.
Molecular and biochemical parasitology. 7(1):27-39 [PMID] 6302505.
View on: PubMed
1983
Scanning electron microscope-analysis of the protrusions (knobs) present on the surface of Plasmodium falciparum-infected erythrocytes.
The Journal of cell biology. 97(3):795-802 [PMID] 6350320.
View on: PubMed
Babesia bovisRad51 ortholog influences switching ofvesgenes but is not essential for segmental gene conversion in antigenic variation
. [DOI] 10.1101/2020.07.06.189316.
Knockout of Babesia bovis rad51 ortholog and its complementation by expression from the BbACc3 artificial chromosome platform
. [DOI] 10.1101/606590.

Grants

Mar 2017 – Apr 2019
Investigation of a shipworm endosymbiont compound with activity against the AIDS-associated pathogens Cryptosporidium and Toxoplasma
Role: Principal Investigator
Funding: WASHINGTON STATE UNIV via NATL CTR FOR COMPLEM AND INTEGRATIVE HLT
May 2016 – Dec 2016
investigation of a shipworm endosymbiont compound with activity against the AIDs associated pathogene cryphosporidium and toxopiasma
Role: Principal Investigator
Funding: TUFTS MEDICAL CENTER via NATL INST OF HLTH

Education

Postdoctoral
1986-1988 · University of Florida
Postdoctoral
1983-1986 · University of Colorado
PhD, Cell Biology
1982 · University of California – Riverside
MS, Biology
1978 · Wayne State University

Teaching Profile

Courses Taught
2007-2021
VEM5131 Vet Molecular Biology
2018
GMS7979 Advanced Research
2018
MCB7979 Advanced Research
2006-2008,2010-2014,2014
VME6934 Topics in Veterinary Medical Sciences
2010
IDH4917 Undergrad Research
2006,2008
VME6464 Molecular Pathogenesis

Contact Details

Phones:
Business:
(352) 294-4126
Emails:
Business:
allredd@ufl.edu

As part of both the Institute of Food and Agricultural Sciences and the Academic Health Center, Veterinary Medicine is dedicated to advancing animal, human and environmental health through teaching, research, extension and patient care.

VISIT IFAS >

Boehringer Ingelheim

The Boehringer Ingelheim Veterinary Scholars Program offers DVM students an opportunity to gain exposure in biomedical research.

LEARN MORE >

Need animal care? Visit the UF Small Animal and Large Animal Hospitals. From dogs, cats, birds and exotics to horses, cattle, llamas, pigs and many other large farm or food animals, our experienced veterinarian staff is ready to assist.

LEARN MORE >