DIFFERENCES AND SIMILARITIES BETWEEN Anaplasma marginale and Anaplasma phagocytophylum

Rev. Salud Anim. Vol. 31 No. 1 (2009): 1-7 Review article DIFFERENCES AND SIMILARITIES BETWEEN Anaplasma marginale AND Anaplasma phagocytophylum Belkis Corona and Siomara Martínez National Centre for Animal and Plant Health (CENSA), Apartado 10, San José de las Lajas, La Habana, Cuba. E-mail: ABSTRACT: Anaplasma marginale and A. phagocytophilum are intracellular rickettsial pathogens causing bovine anaplasmosis and human granulocytic anaplasmosis, respectively. Effective vaccines for the control of anaplasmosis are not available despite attempts using different approaches, such as attenuated strains, infected erythrocyte and tick cell-derived purified antigens. Recent reports demonstrated that A. marginale and A. phagocytophilum co-exist in geographic areas, that concurrent infections may occur in ruminants and ticks and that there are similarities and differences at molecular level between both species. The aim of this article is to make a comparison between the main characteristics of Anaplasma marginale and Anaplasma phagocytophilum. (Key words: Anaplasma marginale; Anaplasma phagocytophilum; major surface proteins) DIFERENCIAS Y SIMILITUDES ENTRE Anaplasma marginale y Anaplasma phagocytophilum RESUMEN: Anaplasma marginale y A. phagocytophilum son rickettsias intracelulares que causan anaplasmosis bovina y anaplasmosis granulocítica humana, respectivamente. Aún no existe una vacuna efectiva para el control de la anaplasmosis, a pesar de haber sido utilizados con este fin cepas atenuadas, eritrocitos infectados y antígenos purificados, derivados de células de garrapatas. Reportes recientes han demostrado que A. marginale y A. phogocytophilum coexisten en áreas geográficas, que infecciones concurrentes pueden ocurrir en rumiantes y garrapatas y que existen similitudes y diferencias a nivel molecular entre estos dos microorganismos. El objetivo de este trabajo es realizar una comparación entre las principales características de A. marginale y A. phagocytophilim. (Palabras clave: Anaplasma marginale; Anaplasma phagocytophilum; proteínas principales de la superficie) Anaplasma marginale A. marginale is a rickettsial organism causing bovine anaplasmosis in cattle with significant economic losses in tropical and subtropical regions worldwide. It invades the erythrocyte and leads to extravascular hemolysis. Ticks are biological vectors of A. marginale but the pathogen is often transmitted mechanically to susceptible cattle by blood-contaminated mouthparts of biting flies or fomites. These obligate intracellular organism replicates in membrane-bound parasitophorous vacuoles in bovine erythrocytes or tick cells. Both cattle and ticks become persistently infected with A. marginale and thus serve as reservoirs of infection (1). Many geographic strains of A. marginale have been identified, which differ in biology, genetic characteristics and transmissibility by ticks. The genetic diversity of A. marginale strains have been characterized using major surface protein (MSP) genes involved in interactions with vertebrate host cells (2). These genes 2 may have evolved more rapidly than other genes because of selective pressures exerted by the host immune system (3). Some studies have demonstrated genetic variation among different A. marginale strains (4), by means of Random Amplified Polymorphic DNA (5); restriction fragment length polymorphism analysis (6), Repetitive Extragenic Consensus (REP/ERIC) PCR patterns (4), PCR assay based on specific sequences of MSP (7;8) and protein sequences (9). de la Fuente et al. (10) results support the hypothesis that genetic heterogenicity observed among strains of A. marginale within endemic regions could be explained by cattle movement and maintenance of different genotypes by independent transmission events, due to infection exclusion of A. marginale in cattle and ticks, which commonly results in the establishment of only one genotype per animal. However, when distantly related genotypes exist in the same region, infections of a single host with multiple A. marginale strains are possible (11). The presence of different A. marginale genotypes in different countries (12) suggests that MSP1a sequences, although conserved during multiplication of the parasite in the bovine host and after transmission by ticks (13), are rapidly changing, resulting in genotype variation within A. marginale populations. For this reason the DNA sequence of the msp1α gene does not provide a distinct phylogeographical resolution, because of its high variability (7;8). In contrast, msp4 sequences may provide useful phylogeographical information (9). Anaplasma marginale can persist in ruminants host for the animal whole life (14). In cattle persistently infected with A. marginale, there are cyclic peaks of rickettsemia every 2 to 6 weeks containing different variants of the immunoprotective major surface protein MSP2 (15). MSP2 is encoded by a multigene family and sequence variation is achieved by segmental gene conversion of a single polycistronic expression site by different pseudogenes. These pseudogenes contain a hypervariable region and portions of flanking 5´and 3´conserved sequences but they are otherwise truncated and cannot encode full-length MSP2 (16). conserved among various isolates of A. marginale (5;18). Antibodies to MSP5 of A. marginale were recognized in both acute stages of infection and chronically infected carrier cattle, a highly sensitive and specific competitive ELISA was developed using this antigen and a monoclonal antibody to MSP5 (19); for these reasons the msp5 gene and the MSP5 protein are the best candidates for Anaplasma marginale diagnosis (20). Anaplasma phagocytophilum The order Rickettsiales represents an obligate intracellular bacteria that reside in vacuoles of eukaryotic cells, with the potential to cause fatal ticktransmitted diseases in humans and several mammalian species. Recent genetic studies reorganized some species within the order Rickettsiales, between the families Rickettsiaceae and Anaplasmataceae (21). Based on these studies, three organisms, formerly known as Ehrlichia phagocytophila, Ehrlichia equi, and the HGE (human granulocytic ehrlichiosis) agent, were unified as a single species and now reclassified as Anaplasma phagocytophilum, the causative agent of granulocytic anaplasmosis, an emerging tick-borne disease in the United State and Europe (22). Closely related to Ehrlichial and Rickettsial organisms, A. phagocytophilum is a small, fragile, Gram-negative bacterium presenting unique challenge for culture, isolation, enumeration, and labelling (23;24). A. phagocytophilum has been worldwide detected, particularly in North America and Europe as well as in South Africa, South America, and Asia (25). Infection with A. phagocytophilum has been recognized in a variety of mammalian hosts, including humans, cats, dogs, horses, ruminants, and wildlife species (26). Clinical disease ranges from mild to fatal, and ass (...truncated)