<i>Anaplasma phagocytophilum</i>and<i>Anaplasma marginale</i>Elicit Different Gene Expression Responses in Cultured Tick Cells

Živković, Zorica; Blouin, Edmour F.; Manzano-Román, Raúl; Almazán, Consuelo; Naranjo, Victoria; Massung, Robert F.; Jongejan, Frans; Kocan, Katherine M.; Fuente, José de la

doi:10.1155/2009/705034

Cited by 31 publications

(56 citation statements)

References 24 publications

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“…As in previous reports (10), the transcriptomics and proteomics results showed differences between cultured tick cells and tick developmental stages and adult tissues in response to pathogen infection, highlighting the presence of tissue-specific differences in the tick cell response to infection (8,12,67). Furthermore, the results of this study are probably relevant for the characterization of the response of tick hemocytes to A. phagocytophilum infection (50,51).…”

Section: Discussionsupporting

confidence: 83%

“…It has been previously shown that the impact of A. phagocytophilum infection on tick cell function is reflected by changes in the transcriptome (8,10,13,14,(53)(54)(55) and proteome (8). However, despite the impact of metabolomics on the study of infectious diseases (15,16), data were not available for ticks.…”

Section: Discussionmentioning

confidence: 99%

“…Previous results demonstrated that tick vector competency involves molecular interactions that ensure that A. phagocytophilum bacteria infect, develop, and are transmitted by ticks (1, 8 -14). Two studies have characterized the tick transcriptome and proteome in response to A. phagocytophilum infection (8,10) and tick proteins have been identified that mediate A. phagocytophilum infection, multiplication, and transmission (1,8,9,(11)(12)(13)(14). Metabolomics is a postgenomic research field concerned with developing methods for analysis of low molecular weight compounds in biological systems such as cells, organs, and organisms.…”

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confidence: 99%

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Integrated Metabolomics, Transcriptomics and Proteomics Identifies Metabolic Pathways Affected by Anaplasma phagocytophilum Infection in Tick Cells*

Villar

Ayllón

Alberdi

et al. 2015

Molecular & Cellular Proteomics

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Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human granulocytic anaplasmosis. These intracellular bacteria establish infection by affecting cell function in both the vertebrate host and the tick vector, Ixodes scapularis. Previous studies have characterized the tick transcriptome and proteome in response to A. phagocytophilum infection. However, in the postgenomic era, the integration of omics datasets through a systems biology approach allows network-based analyses to describe the complexity and functionality of biological systems such as host-pathogen interactions and the discovery of new targets for prevention and control of infectious diseases. This study reports the first systems biology integration of metabolomics, transcriptomics, and proteomics data to characterize essential metabolic pathways involved in the tick response to A. phagocytophilum infection. The ISE6 tick cells used in this study constitute a model for hemocytes involved in pathogen infection and immune response. The results showed that infection affected protein processing in endoplasmic reticulum and glucose metabolic pathways in tick cells. These results supported tick-Anaplasma co-evolution by providing new evidence of how tick cells limit pathogen infection, while the pathogen benefits from the tick cell response to establish infection. Additionally, ticks benefit from A. phagocytophilum infection by increasing survival while pathogens guarantee transmission. The results suggested that A. phagocytophilum induces protein misfolding to limit the tick cell response and facilitate infection but requires protein degradation to prevent ER stress and cell apoptosis to survive in infected cells. Additionally, A. phagocytophilum may benefit from the tick cell's ability to limit bacterial infection through PEPCK inhibition leading to decreased glucose metabolism, which also results in the inhibition of cell apoptosis that increases infection of tick cells. These results support the use of this experimental approach to systematically identify cell pathways and molecular mechanisms involved in tick-pathogen interactions. Data are available via ProteomeXchange with identifier PXD002181. Molecular & Cellular

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Integrated Metabolomics, Transcriptomics and Proteomics Identifies Metabolic Pathways Affected by Anaplasma phagocytophilum Infection in Tick Cells*

Villar

Ayllón

Alberdi

et al. 2015

Molecular & Cellular Proteomics

Self Cite

108

190

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“…While A. phagocytophilum has been shown to infect I. scapularis gut cells (9) and salivary glands (10), the developmental cycle of this pathogen has not been described in ticks. Tick proteins such as Salp16, subolesin, antifreeze glycoprotein IAFGP, and alpha1-3-fucosyltransferease were differentially regulated and required for A. phagocytophilum infection of I. scapularis (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Activation of heat shock proteins and other stress response proteins in ticks and cultured tick cells in response to A. phagocytophilum infection was also characterized by proteomics and transcriptomics analyses (21).…”

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confidence: 99%

Anaplasma phagocytophilum Inhibits Apoptosis and Promotes Cytoskeleton Rearrangement for Infection of Tick Cells

et al. 2013

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dAnaplasma phagocytophilum causes human granulocytic anaplasmosis. Infection with this zoonotic pathogen affects gene expression in both the vertebrate host and the tick vector, Ixodes scapularis. Here, we identified new genes, including spectrin alpha chain or alpha-fodrin (CG8) and voltage-dependent anion-selective channel or mitochondrial porin (T2), that are involved in A. phagocytophilum infection/multiplication and the tick cell response to infection. The pathogen downregulated the expression of CG8 in tick salivary glands and T2 in both the gut and salivary glands to inhibit apoptosis as a mechanism to subvert host cell defenses and increase infection. In the gut, the tick response to infection through CG8 upregulation was used by the pathogen to increase infection due to the cytoskeleton rearrangement that is required for pathogen infection. These results increase our understanding of the role of tick genes during A. phagocytophilum infection and multiplication and demonstrate that the pathogen uses similar strategies to establish infection in both vertebrate and invertebrate hosts.T icks are ectoparasites of animals and humans and are considered to be the most important arthropod vector of pathogens in some regions (1). Ixodes scapularis Say (Acari: Ixodidae) is an important vector of pathogens that infect and cause disease in humans and domestic animals in the United States. Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae), the focus of this study, is the causative agent of human, canine, and equine granulocytic anaplasmosis and tick-borne fever of ruminants (2, 3).A. phagocytophilum is an intracellular bacterium that infects vertebrate host neutrophils, where it multiplies within a parasitophorous vacuole, thus evading host defenses while inhibiting apoptosis and promoting cytoskeleton rearrangement for infection and multiplication (4-8). Tick-A. phagocytophilum interactions are not as well characterized as those between pathogen and vertebrate hosts (4). While A. phagocytophilum has been shown to infect I. scapularis gut cells (9) and salivary glands (10), the developmental cycle of this pathogen has not been described in ticks. Tick proteins such as Salp16, subolesin, antifreeze glycoprotein IAFGP, and alpha1-3-fucosyltransferease were differentially regulated and required for A. phagocytophilum infection of I. scapularis (10-20). Activation of heat shock proteins and other stress response proteins in ticks and cultured tick cells in response to A. phagocytophilum infection was also characterized by proteomics and transcriptomics analyses (21).The overall goal of our research is to characterize molecular interactions at the vector-pathogen interface and develop vaccines for the control of tick infestations and pathogen infection/transmission. Our hypothesis is that tick genes differentially expressed in response to pathogen infection would include those involved in pathogen infection, multiplication, and transmission, as well as in the tick protective response to infection. In this researc...

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“…Moreover, endothelial cell lines are useful for studying A. marginale infection in vitro, as they are the only mammalian cell types in which continuous cultivation of these microbes has been achieved (7,8). The immortalized tick cell line ISE6 is susceptible to A. marginale infection and supports its replication, making it a useful model for studying bacteriumtick cell interactions (9)(10)(11).…”

mentioning

confidence: 99%

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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Anaplasma phagocytophilumandAnaplasma marginaleElicit Different Gene Expression Responses in Cultured Tick Cells

Cited by 31 publications

References 24 publications

Integrated Metabolomics, Transcriptomics and Proteomics Identifies Metabolic Pathways Affected by Anaplasma phagocytophilum Infection in Tick Cells*

Integrated Metabolomics, Transcriptomics and Proteomics Identifies Metabolic Pathways Affected by Anaplasma phagocytophilum Infection in Tick Cells*

Anaplasma phagocytophilum Inhibits Apoptosis and Promotes Cytoskeleton Rearrangement for Infection of Tick Cells

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

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