Human Granulocytic Anaplasmosis (HGA) was first recognized in the United States and is the most common tick-borne disease after Borreliosis. It is endemic in 42 countries with an overall case fatality of 5%. The causative agent of HGA is the rickettsial species Anaplasma phagocytophilum
, a Gram-negative obligate intracellular pathogen infecting mammalian hosts worldwide. It invades and replicates within neutrophils by employing an array of mechanisms to subvert their bactericidal activity. Characteristic is the development of intracytoplasmic morulae within those peripheral blood granulocytes. Several epitopes on surface proteins of Anaplasma phagocytophilum
are targeted during an immune response.
Major outer membrane protein A (OmpA) of A. phagocytophilum
is a peptidoglycan-binding lipoprotein, transcriptionally upregulated during tick transmission feeding and playing an important role in the pathogenesis of HGA. The integral outer membrane channel belongs to the porin superfamily, which share a beta-barrel structure.
The invasion domain of OmpA is conserved in all Anaplasma
species. Invasion is mediated by interaction of the protein with α2,3-sialic acid of the sialyl Lewis x (sLex) tetrasaccharide, which caps P-selectin glycoprotein ligand-1 (PSGL-1) and other glycoproteins on eukaryotic cell surfaces. Binding of the bacterium to these receptors on the membrane promotes endocytosis. Therefore, the invasin OmpA, together with other proteins, is important for entry into mammalian cells and critical for infection of neutrophils in host cells. Using an agonist for OmpA receptors, e.g. glutathione S-transferase (GST)–OmpA, shows that A. phagocytophilum
infection of host cells is reduced by approximately 50 % as it blocks access of native OmpA on the bacterial surface to sialic acids.
Until now, DIARECT has provided the immunodominant major surface protein 5 (Msp5), also present in the salivary glands of infected ticks, and A. phagocytophilum
p44, a transmembrane protein of the outer membrane, which is thought to enable the bacterium to avoid host immune surveillance. To complete the Anaplasma product line, DIARECT is now offering a third A. phagocytophilum
antigen produced in E. coli
to expand this product line: OmpA. All three proteins are considered main antigens of antibody response to HGA.References: Atifi et al. (2015) Parasitol Res. DOI 10.1007/s00436-015-4698-2 Blanco and Oteo (2002) Clin Microbiol and Infect. 8: 763–772 Chen et al. (1994) J Clin Microbiol. 32:589–595 Ijdo et al. (1998) Infect Immun. 66: 3264–3269 Kahlon et al. (2013) Infect Immun. 81:65-79 Knowles et al. (1996) J Clin Microbiol. 34: 2225-2230 Lotric-Furlan et al. (1998) Clin Infect Dis. 27: 424–428 Ojogun et al. (2012) Infect Immun. 80: 3748–3760 Palmer et al. (1994) J Clin Microbiol. 42:5381–5384 Park et al. (2003) Infect Immun. 71: 4018–4025 Rikihisa et al. (2007) Journal Bacteriol. 189: 7819–7828 Wang et al. (2013) PLoS One. 8 (10): e78189
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