Subdominant Outer Membrane Antigens in Anaplasma marginale: Conservation, Antigenicity, and Protective Capacity Using Recombinant Protein

Ducken, Deirdre; Brown, Wendy C.; Alperin, Debra C.; Brayton, Kelly A.; Reif, Kathryn E.; Turse, Joshua E.; Palmer, Guy H.; Noh, Susan M.

doi:10.1371/journal.pone.0129309

Cited by 25 publications

(42 citation statements)

References 47 publications

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“…Thus, even though full-length AmOmpA is immunogenic, the region that carries its functional domain is not. The poor immunogenicity of this AmOmpA region is consistent with it being designated a subdominant epitope and our findings that A. phagocytophilum infection does not yield a strong anti-ApOmpA humoral immune response (14,16,17). This makes sense from a pathobiological standpoint: an adhesin that is important for invasion and thus survival of an obligate intracellular bacterium would presumably be counterproductive if its functional domain were highly immunogenic.…”

Section: Discussionsupporting

confidence: 72%

“…Immunization with an A. marginale outer membrane fraction protects against bacteremia and disease after experimental challenge. However, this outer membrane preparation contains over 20 proteins and is difficult to concoct and standardize (14). Accordingly, it has been proposed that a recombinant subunit vaccine would be ideal, as it would reduce time and cost of production (2) in addition to being safer.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…marginale expresses the surface protein OmpA (outer membrane protein A; AM854 in the St. Maries strain) (13) during infection of cattle (14)(15)(16). OmpA is highly conserved among A. marginale sensu stricto strains and isolates, exhibiting 99.6 to 100% identity (14). Clues pertaining to the role of A. marginale OmpA (AmOmpA) are provided by recent studies demonstrating the importance of OmpA proteins to cellular invasion by A. phagocytophilum and Ehrlichia chaffeensis, two Anaplasmataceae members that cause potentially fatal infections of humans and animals (17)(18)(19).…”

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confidence: 99%

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Anaplasma marginale Outer Membrane Protein A Is an Adhesin That Recognizes Sialylated and Fucosylated Glycans and Functionally Depends on an Essential Binding Domain

et al. 2017

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Anaplasma marginale causes bovine anaplasmosis, a debilitating and potentially fatal tick-borne infection of cattle. Because A. marginale is an obligate intracellular organism, its adhesins that mediate entry into host cells are essential for survival. Here, we demonstrate that A. marginale outer membrane protein A (AmOmpA; AM854) contributes to the invasion of mammalian and tick host cells. AmOmpA exhibits predicted structural homology to OmpA of A. phagocytophilum (ApOmpA), an adhesin that uses key lysine and glycine residues to interact with ␣2,3-sialylated and ␣1,3-fucosylated glycan receptors, including 6-sulfo-sialyl Lewis x (6-sulfo-sLe x ). Antisera against AmOmpA or its predicted binding domain inhibits A. marginale infection of host cells. Residues G55 and K58 are contributory, and K59 is essential for recombinant AmOmpA to bind to host cells. Enzymatic removal of ␣2,3-sialic acid and ␣1,3-fucose residues from host cell surfaces makes them less supportive of AmOmpA binding. AmOmpA is both an adhesin and an invasin, as coating inert beads with it confers adhesiveness and invasiveness. Recombinant forms of AmOmpA and ApOmpA competitively antagonize A. marginale infection of host cells, but a monoclonal antibody against 6-sulfo-sLe x fails to inhibit AmOmpA adhesion and A. marginale infection. Thus, the two OmpA proteins bind related but structurally distinct receptors. This study provides a detailed understanding of AmOmpA function, identifies its essential residues that can be targeted by blocking antibody to reduce infection, and determines that it binds to one or more ␣2,3-sialylated and ␣1,3-fucosylated glycan receptors that are unique from those targeted by ApOmpA.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Anaplasma marginale Outer Membrane Protein A Is an Adhesin That Recognizes Sialylated and Fucosylated Glycans and Functionally Depends on an Essential Binding Domain

et al. 2017

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“…Western blotting and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were performed to ensure that the anti-Rab-GTPase antibodies and organelle markers did not cross-react with A. marginale proteins and that they recognized the appropriate D. andersoni proteins. For Western blot assays, 50 g of total proteins from lysates of DAE100T cells and 50 g of uninfected and 50 g of A. marginale-infected bovine erythrocytes, which were washed to remove leukocytes, were analyzed by immunoblotting as previously de- scribed (24), with the exception that the separated proteins were transferred to a polyvinylidene fluoride membrane (Millipore) rather than to nitrocellulose. No proteins were detected in either A. marginale-infected or uninfected erythrocytes, and the antibodies did not cross-react with each other or bind nonspecifically to the culture cells and A. marginale ( Fig.…”

Section: Methodsmentioning

confidence: 99%

Anaplasma marginale Actively Modulates Vacuolar Maturation during Intracellular Infection of Its Tick Vector, Dermacentor andersoni

Magunda

Thompson

Schneider

et al. 2016

Appl Environ Microbiol

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Tick-borne transmission of bacterial pathogens in the order Rickettsiales is responsible for diverse infectious diseases, many of them severe, in humans and animals. Transmission dynamics differ among these pathogens and are reflected in the pathogenvector interaction. Anaplasma marginale has been shown to establish and maintain infectivity within Dermacentor spp. for weeks to months while escaping the complex network of vacuolar peptidases that are responsible for digestion of the tick blood meal. How this prolonged maintenance of infectivity in a potentially hostile environment is achieved has been unknown. Using the natural vector Dermacentor andersoni, we demonstrated that A. marginale-infected tick vacuoles (AmVs) concurrently recruit markers of the early endosome (Rab5), recycling endosome (Rab4 and Rab11), and late endosome (Rab7), are maintained near neutral pH, do not fuse with lysosomes, exclude the protease cathepsin L, and engage the endoplasmic reticulum and Golgi apparatus for up to 21 days postinfection. Maintenance of this safe vacuolar niche requires active A. marginale protein synthesis; in its absence, the AmVs mature into acidic, protease-active phagolysosomes. Identification of this bacterially directed modeling of the tick midgut endosome provides a mechanistic basis for examination of the differences in transmission efficiency observed among A. marginale strains and among vector populations. T icks are biological vectors of the obligate intracellular bacteria of the order Rickettsiales, including pathogens that cause severe diseases in humans and animals (1). Transmission dynamics determine the epidemiologic features of a given disease and vary among the pathogen-vector pairs. For example, Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, is maintained in the tick vector Dermacentor andersoni through transovarial transmission, and thus each new generation of larval ticks is infected. Additionally, infection is maintained with each successive molt, circumventing the need for feeding on an infected mammalian host to maintain the pathogen through time. In contrast, Anaplasma marginale, responsible for anaplasmosis in ruminants, must be acquired and transstadially transmitted by each new generation of adult D. andersoni ticks (2). It is not transovarially transmitted, and the larvae and nymphs of D. andersoni are not exposed to A. marginale because they feed preferentially on small mammals. Adult male ticks feed preferentially on cattle, move between hosts while seeking mates, and thus are the epidemiologically important transmission vector. Consequently, A. marginale must persist in the tick for the period of time necessary for an adult tick to ingest two separate blood meals, which depending on conditions, may occur in separate seasons. Experimentally infected adult male D. andersoni ticks are able to transmit A. marginale for up to 26 days after acquisition feeding (2-4). The mechanisms by which pathogens maintain long-term infections within ticks remain po...

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Anaplasma marginale outer membrane protein vaccine candidates are conserved in North American and South African strains

Hove

Brayton

Liebenberg

et al. 2020

Ticks and Tick-borne Diseases

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Subdominant Outer Membrane Antigens in Anaplasma marginale: Conservation, Antigenicity, and Protective Capacity Using Recombinant Protein

Cited by 25 publications

References 47 publications

Anaplasma marginale Outer Membrane Protein A Is an Adhesin That Recognizes Sialylated and Fucosylated Glycans and Functionally Depends on an Essential Binding Domain

Anaplasma marginale Outer Membrane Protein A Is an Adhesin That Recognizes Sialylated and Fucosylated Glycans and Functionally Depends on an Essential Binding Domain

Anaplasma marginale Actively Modulates Vacuolar Maturation during Intracellular Infection of Its Tick Vector, Dermacentor andersoni

Anaplasma marginale outer membrane protein vaccine candidates are conserved in North American and South African strains

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