title: Genome-wide diversity and gene expression profiling of Babesia microti isolates identify polymorphic genes that mediate host-pathogen interactions.
abstract: Babesia microti, a tick-transmitted, intraerythrocytic protozoan parasite circulating mainly among small mammals, is the primary cause of human babesiosis. While most cases are transmitted by Ixodes ticks, the disease may also be transmitted through blood transfusion and perinatally. A comprehensive analysis of genome composition, genetic diversity, and gene expression profiling of seven B. microti isolates revealed that genetic variation in isolates from the Northeast United States is almost exclusively associated with genes encoding the surface proteome and secretome of the parasite. Furthermore, we found that polymorphism is restricted to a small number of genes, which are highly expressed during infection. In order to identify pathogen-encoded factors involved in host-parasite interactions, we screened a proteome array comprised of 174 B. microti proteins, including several predicted members of the parasite secretome. Using this immuno-proteomic approach we identified several novel antigens that trigger strong host immune responses during the onset of infection. The genomic and immunological data presented herein provide the first insights into the determinants of B. microti interaction with its mammalian hosts and their relevance for understanding the selective pressures acting on parasite evolution.
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.|Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Joana C
authors.initials: JC
authors.lastname: Silva
authors.affiliation: Institut de Biologie Computationnelle, IBC, Université de Montpellier, 860 rue St Priest, Bat 5 - CC05019, 34095 Montpellier, Cedex 5, France.|Institut de Recherche en Cancérologie de Montpellier, IRCM - INSERM U896 &Université de Montpellier &ICM, Institut régional du Cancer Montpellier, Campus Val d'Aurelle, 34298 Montpellier, Cedex 5 France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Cornillot
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: McCracken
authors.affiliation: Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, 15 York St., New Haven, Connecticut, CT 06520 USA.|Yale School of Public Health and Yale School of Medicine, 60 College St., New Haven, Connecticut, CT 06520 USA.
authors.forename: Sahar
authors.initials: S
authors.lastname: Usmani-Brown
authors.affiliation: Institut de Biologie Computationnelle, IBC, Université de Montpellier, 860 rue St Priest, Bat 5 - CC05019, 34095 Montpellier, Cedex 5, France.|Institut de Recherche en Cancérologie de Montpellier, IRCM - INSERM U896 &Université de Montpellier &ICM, Institut régional du Cancer Montpellier, Campus Val d'Aurelle, 34298 Montpellier, Cedex 5 France.
authors.forename: Ankit
authors.initials: A
authors.lastname: Dwivedi
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Olukemi O
authors.initials: OO
authors.lastname: Ifeonu
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Crabtree
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Hanzel T
authors.initials: HT
authors.lastname: Gotia
authors.affiliation: Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, 15 York St., New Haven, Connecticut, CT 06520 USA.
authors.forename: Azan Z
authors.initials: AZ
authors.lastname: Virji
authors.affiliation: Institut de Genomique Fonctionnelle, IGF - CNRS UMR 5203, 141 rue de la cardonille, 34094 Montpellier, Cedex 05, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Reynes
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier, IRCM - INSERM U896 &Université de Montpellier &ICM, Institut régional du Cancer Montpellier, Campus Val d'Aurelle, 34298 Montpellier, Cedex 5 France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Colinge
authors.affiliation: Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, 15 York St., New Haven, Connecticut, CT 06520 USA.
authors.forename: Vidya
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, 15 York St., New Haven, Connecticut, CT 06520 USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Lawres
authors.affiliation: Antigen Discovery Inc., Irvine, CA, 92618 USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Pazzi
authors.affiliation: Antigen Discovery Inc., Irvine, CA, 92618 USA.
authors.forename: Jozelyn V
authors.initials: JV
authors.lastname: Pablo
authors.affiliation: Antigen Discovery Inc., Irvine, CA, 92618 USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Hung
authors.affiliation: Yale School of Public Health and Yale School of Medicine, 60 College St., New Haven, Connecticut, CT 06520 USA.
authors.forename: Jana
authors.initials: J
authors.lastname: Brancato
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Priti
authors.initials: P
authors.lastname: Kumari
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Orvis
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Tretina
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.|Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Marcus
authors.initials: M
authors.lastname: Chibucos
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Sandy
authors.initials: S
authors.lastname: Ott
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Sadzewicz
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Sengamalay
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Amol C
authors.initials: AC
authors.lastname: Shetty
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Su
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Luke
authors.initials: L
authors.lastname: Tallon
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD 21201 USA.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Fraser
authors.affiliation: Université de Montpellier, IES, UMR 5214, 860 rue de St Priest, Bt5, 34095 Montpellier, France.|CIRAD, UMR 17, Cirad-Ird, TA-A17/G, Campus International de Baillarguet, 34398 Montpellier, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Frutos
authors.affiliation: Antigen Discovery Inc., Irvine, CA, 92618 USA.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Molina
authors.affiliation: Yale School of Public Health and Yale School of Medicine, 60 College St., New Haven, Connecticut, CT 06520 USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Krause
authors.affiliation: Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, 15 York St., New Haven, Connecticut, CT 06520 USA.
authors.forename: Choukri
authors.initials: C
authors.lastname: Ben Mamoun
mesh_terms: D000818:Animals; D041001:Babesia microti / Q000235:genetics / Q000472:pathogenicity*; D001404:Babesiosis / Q000235:genetics* / Q000469:parasitology / Q000635:transmission; D005786:Gene Expression Regulation; D018503:Genome, Protozoan; D023281:Genomics; D006790:Host-Parasite Interactions / Q000235:genetics; D006801:Humans; D018884:Ixodes / Q000235:genetics / Q000469:parasitology; D046228:Microarray Analysis; D009511:New England; D011110:Polymorphism, Genetic; D040901:Proteomics