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PubMed1996

Developmental studies of Anaplasma marginale (Rickettsiales:Anaplasmataceae) in male Dermacentor andersoni (Acari:Ixodidae) infected as adults by using nonradioactive in situ hybridization and microscopy.

The development of Anaplasma marginale Theiler was studied in ticks using a nonradioactive in situ hybridization method developed in our laboratory. Male Rocky Mountain wood ticks, Dermacentor andersoni Stiles, were infected intrastadially by allowing them to feed for 7 d on an infected calf (acquisition feeding). The ticks were then removed and held in a humidity chamber for 5 d before being fed on a 2nd susceptible call for 10 d (transmission feeding). Two groups of 10 ticks were collected daily during the 22-d experiment. In one group one-half of each tick was processed and embedded in paraffin and in the other group one-half of each tick was embedded in LR White for in situ hybridization. The companion tick halves from each group were fixed and embedded in Dow Epoxy Resin resin for routine light and electron microscopy. As detected by in situ hybridization on LR White- and paraffin-embedded sections and by microscopy, initial infection of A. marginale in ticks occurred in gut tissues either on the 7th d of acquisition feeding or the 1st d of the held period and infection persisted throughout transmission feeding. The highest number of ticks with gut infection was observed on the 5th d of transmission feeding. Salivary glands became infected with A. marginale on the 1st day of transmission feeding and remained infected throughout the transmission feeding period. Peak infection was observed on day 4 of transmission feeding. After the beginning of transmission feeding, A. marginale infection was also observed in interstitial, reproductive, skeletal muscle, fat body, and Malpighian tubule tissues. Although A. marginale infection of ticks clearly originates in midgut epithelial cells, many tissues eventually become infected during transmission feeding, resulting in a generalized infection. The infection of multiple tissues may contribute to the ability of A. marginale infection to persist in intrastadially infected male ticks.

Anaplasma↗
PubMed1998

Morphology and development of Anaplasma marginale (Rickettsiales: Anaplasmataceae) in cultured Ixodes scapularis (Acari: Ixodidae) cells.

Anaplasma marginale Theiler, a tick-borne rickettsial pathogen of cattle, was recently propagated in a continuous tick cell line, IDE8, derived from embryonic Ixodes scapularis Say. Cell monolayers were infected briefly with a high multiplicity of infection to synchronize rickettsial development and allow for description of the invasion, development, and release of A. marginale from the cultured cells. Sequential samples were collected, fixed, and processed for examination with light and electron microscopy. A. marginale entered host cells by an endocytotic process and remained within a vacuolar membrane throughout development. After entry, the dense form of A. marginale transformed into the vegetative or reticulated form that multiplied by binary fission, forming large colonies of rickettsiae. The reticulated form subsequently transformed into the dense form of A. marginale, which was released from cells and survived extracellularly. The dense forms were eventually released from the cultured cells by a process in which the inclusion membrane fused with the host cell membrane. Release of A. marginale was effected without the loss of host cell cytoplasm. In subsequent cell cycles, A. marginale reinfected cultured cells resulting in the development of multiple colonies per cell and eventual host cell destruction. Small vesicles were abundant within the colonies and appeared to form from individual rickettsiae. Development of A. marginale in IDE8 cells was similar to that described in naturally infected Dermacentor spp. ticks. However, destruction of cells by A. marginale as seen in vitro was not observed in naturally infected ticks. An understanding of the developmental cycle of A. marginale in cultured cells may provide insight into rickettsial development in its tick host and provide a basis for studying pathogen-host cell interaction in vitro.

Anaplasma↗
PubMed2005

Relative encounter frequencies and prevalence of selected Borrelia, Ehrlichia, and Anaplasma infections in Amblyomma americanum and Ixodes scapularis (Acari: Ixodidae) ticks from central New Jersey.

To evaluate their relative importance in tick-borne disease transmission in New Jersey, host-seeking Amblyomma americanum (L.) and Ixodes scapularis Say adults and nymphs were collected during spring activity periods in 2003 and 2004 to determine relative frequencies at which these ticks were encountered from an area known to be hyperendemic for Lyme disease. Although similar numbers of the two species were encountered during early spring of both years, A. americanum were encountered more often later in the season and exhibited a longer activity period than I. scapularis. A. americanum nymphs were collected at frequencies between 2.6 and 7.3 times higher than I. scapularis nymphs. Polymerase chain reaction (PCR) analysis of 121 A. americanum adults yielded infection prevalences of 9.1% for Borrelia lonestari, 12.3% for Ehrlichia chaffeenensis, and 8.2% for E. ewingii, and coinfection prevalences of 4.1% for E. chaffeensis/E. ewingii and 0.8% for E. chaffeensis/B. lonestari. Infection prevalences in 147 I. scapularis adults were 50.3% for B. burgdorferi, 6.1% for Anaplasma (Ehrlichia) phagocytophilum, and 1.4% for a recently described novel Borrelia species, whereas the coinfection prevalences were 2.7% for B. burgdorferi/A. phagocytophilum, 0.7% for B. burgdorferi/novel Borrelia, and 0.7% for A. phagocytophilum/novel Borrelia. The B. burgdorferi infection prevalence in I. scapularis was considerably higher than that in A. americanum. However, the higher A. americanum encounter frequencies compared with I. scapularis may result in increased risk of acquiring exposure to A. americanum-transmitted pathogens. The potential public health implications of these results are discussed.

Anaplasma↗
PubMed2005

Capillary tube feeding system for studying tick-pathogen interactions of Dermacentor variabilis (Acari: Ixodidae) and Anaplasma marginale (Rickettsiales: Anaplasmataceae).

A capillary tube feeding (CTF) system was adapted for studying the interaction between Dermacentor variabilis (Say) and the rickettsial cattle pathogen Anaplasma marginale Theiler. A. marginale undergoes a complex developmental cycle in ticks that begins in midguts and ends by transmission from salivary glands. In this CTF system, male D. variabilis were fed A. marginale-infected blood or cultured tick cells. Ticks that fed on highly rickettsemic calves developed midgut and salivary gland infections as detected by PCR, whereas ticks that were fed from capillary tubes on the same blood developed only midgut infections. An unexpected result of capillary tube feeding was that antibodies against the A. marginale adhesin, major surface protein la, enhanced midgut infections and caused cell culture-derived A. marginale to infect midguts. Another unexpected result was the infection of the midguts of the nonvector tick Amblyomma americanum (L.), after capillary tube feeding on infected bovine blood. The gut cell response of ticks to A. marginale, as determined from SDS-polyacrylamide gel electrophoresis protein profiles, did not differ when ticks were fed infected or uninfected cells from capillary tubes. Selected protein bands, as identified by tryptic digestion-mass spectrometry, contained mostly proteins of bovine origin, including bovine albumin, undigested alpha- and beta-chain hemoglobin and hemoglobin fragments. Although infection of ticks by A. marginale CTF system was not the same as infection by feeding on cattle, the results obtained demonstrated the potential use of this system for identifying aspects of pathogen-vector interactions that are not readily recognized in naturally feeding ticks.

Adhesins, Bacterial↗
PubMed2006

Mechanisms of evasion of neutrophil killing by Anaplasma phagocytophilum.

PURPOSE OF REVIEW: This review summarizes recent knowledge regarding the strategies employed by Anaplasma phagocytophilum to evade or subvert neutrophil killing mechanisms and modify other neutrophil pathways to promote its survival. RECENT FINDINGS: A. phagocytophilum evades neutrophil oxidative killing by preventing fusion of cytochrome b558-carrying specific granules and secretory vesicles with the membrane of its cytoplasmic compartment. It also directly detoxifies superoxide anion. Additionally, the bacterium alters the interaction of transcription factors with the CYYB promoter, which results in greatly reduced gp91phox levels and a consequent decline in respiratory burst capability. A. phagocytophilum not only fails to activate the normal neutrophil apoptosis differentiation program stimulated by bacterial uptake, but also delays spontaneous apoptosis by manipulating the expression of pro and antiapoptotic genes. Maintenance of the proapoptotic factor Bfl-1 contributes, at least in part, to the preservation of mitochondrial membrane integrity and inhibition of caspase 3 activation. SUMMARY: A. phagocytophilum combats neutrophil oxidative killing by scavenging O2, inhibiting NADPH oxidase assembly on its vacuolar membrane, and modifying promoter activity for a key NADPH oxidase component, gp91phox. Uptake of this unique pathogen fails to induce neutrophil apoptosis. Furthermore, A. phagocytophilum extends the life of its otherwise short-lived host cell by dysregulating neutrophil gene expression and molecular machinery to potentially maximize its survival and dissemination within its mammalian host.

Anaplasma phagocytophilum↗
PubMed1992

Phylogenetic relationship of Cowdria ruminantium, agent of heartwater, to Anaplasma marginale and other members of the order Rickettsiales determined on the basis of 16S rRNA sequence.

The phylogenetic relationship between Cowdria ruminantium and representative members of the orders Rickettsiales and Chlamydiales has been examined on the basis of the sequence of the 16S rRNA. Phylogeny reconstruction by using both parsimony and distance methods supports the conclusion that C. ruminantium is closely related to the Rickettsiales and in particular to the family Anaplasmataceae. A signature of nine base substitutions delineated the linkage of Anaplasma marginale with C. ruminantium and differentiated these two species from the 45 other members of the alpha group of Proteobacteria examined, and five of these base substitutions were unique among all members of the class Proteobacteria examined to date.

Alphaproteobacteria↗
PubMed2001

Phylogenetic relationships of Anaplasma marginale and 'Ehrlichia platys' to other Ehrlichia species determined by GroEL amino acid sequences.

The heat-shock protein (GroEL) genes of Anaplasma marginale, Ehrlichia muris and 'Ehrlichia platys' were sequenced and compared with the GroEL of other species of Ehrlichia. The GroEL amino acid sequences of A. marginale and 'E. platys' were most similar to the GroEL sequence of Ehrlichia phagocytophila, with which they formed one group with 6-10% divergence. The E. muris GroEL was most closely related to the GroEL of two unclassified strains (HF-565 and Anan), then to Ehrlichia chaffeensis, Ehrlichia canis, Ehrlichia ewingii and Cowdria ruminantium, forming a second distinct group (0.3-8.6% divergence). The GroELs of Ehrlichia risticii and Ehrlichia sennetsu were very similar to one another (only 2% divergence), forming the third group. The first two groups were relatively closely related (17-20% divergence), while the third group was only distantly related to the first two groups (62-73% divergence).

Amino Acid Sequence↗
PubMed1993

Analysis of the Anaplasma marginale genome by pulsed-field electrophoresis.

Anaplasma marginale is a rickettsial parasite of bovine erythrocytes causing world-wide economic losses in livestock production. Despite its importance, little is known about this rickettsia at a molecular level because it has not been cultured in vitro, and there is no small-animal model. Although several genes have been cloned and sequenced, the gross genome structure of the organism has not yet been well characterized. We separated intact bovine erythrocytes from leucocytes, and determined the genome size of A. marginale by use of restriction endonuclease cleavage and pulsed-field gel electrophoresis (PFGE). A value of 56 mol% G+C was obtained for this genome by spectral analysis. Undigested A. marginale DNA failed to migrate under several different electrophoretic conditions, indicating a circular genome. Digestions of intact A. marginale DNA were performed using restriction endonucleases NotI, SfiI and PacI. Complete digestion with SfiI resulted in 12 distinct bands ranging in size from 14 to 170 kbp. Total size determined by addition of SfiI-digested fragments was approximately 1200 kbp. PacI cleaved the A. marginale genome from three different isolates into just three fragments, of 598, 557 and 97 kbp. Incomplete digestion produced a band measuring 1250 kbp. These results indicate that A. marginale has a circular genome between 1200 and 1260 kbp, with a G+C content of 56 mol%.

Anaplasma↗
PubMed2004

Groupings of highly similar major surface protein (p44)-encoding paralogues: a potential index of genetic diversity amongst isolates of Anaplasma phagocytophilum.

Anaplasma phagocytophilum is a tick-borne bacterium that is zoonotic in the USA and southern Europe, but although the bacterium is endemic in the UK, no cases of clinical human disease have yet been detected in that country. Potential genomic differences amongst UK and USA isolates were investigated by comparing partial 16S rRNA gene and p44 paralogue sequences amplified by PCR from 10 UK ruminant or tick isolates, with published sequences from USA isolates. No significant clustering among the isolates was resolved by phylogenetic analysis of alignments containing 16S rRNA gene sequences. The structure of predicted proteins encoded by p44 paralogues, amplified from 81 clones obtained from the UK isolates, was similar to that described previously for paralogues from USA isolates. Paralogue sequences did not obviously cluster by country, host species or isolate, but most paralogues were 30-70 % similar, making meaningful alignments difficult. Some p44 paralogues from different isolates formed clusters of sequences that were more than 90 % similar to one another ('similarity groups'). The paralogues in each cluster were particularly similar in gene regions most likely to code for ligands. In the sample studied, 95 % of the similarity groups comprised paralogues from either USA or UK isolates only and occurred with greater frequency amongst paralogues from USA rather than UK isolates. These findings raise the hypothesis that sequences of paralogues in similarity groups may provide an index of adaptation of different 'strains' of A. phagocytophilum to specific reservoir hosts in different geographical locations, and any associations with infectivity for different species including humans.

Amino Acid Sequence↗
PubMed2006

Reduced number of interleukin-12 secreting cells in patients with Lyme borreliosis previously exposed to Anaplasma phagocytophilum.

Lyme borreliosis and human granulocytic ehrlichiosis are tick-borne diseases caused by Borrelia burgdorferi and Anaplasma phagocytophilum, respectively. Infection with A. phagocytophilum has been observed to induce immunosuppression and animal studies suggest that the bacteria might also have prolonged inhibitory effects on immune cells. The aim of this study was to investigate the cytokine secretion in patients exposed previously to A. phagocytophilum and currently infected with B. burgdorferi compared with patients infected with B. burgdorferi and seronegative for A. phagocytophilum. Eight patients with erythema migrans and antibodies against A. phagocytophilum, 15 patients with erythema migrans and negative A. phagocytophilum serology and 15 non-exposed healthy individuals were included in the study. Blood mononuclear cells were stimulated with Borrelia-antigen and the number of cytokine [interleukin (IL)-4, IL-5, IL-12, IL-13 and interferon (IFN)-gamma]-secreting cells was detected by enzyme-linked immunospot (ELISPOT). This study shows that patients with a previous exposure to A. phagocytophilum and a current infection with B. burgdorferi have a lower number of Borrelia-specific cells secreting IL-12 compared to Ap seronegative patients infected with B. burgdorferi (P < 0.001), indicating impairment in the ability to mount strong Th1-responses. We suggest that this mirrors a reduced Th1 response caused by A. phagocytophilum which could influence the outcome of the Borrelia infection and, speculatively, may also have implications in other conditions.

Adolescent↗
PubMed2006

Flow cytometric evaluation of selected antimicrobial efficacy for clearance of Anaplasma marginale in short-term erythrocyte cultures.

The tick-borne rickettsia, Anaplasma marginale, causes the economically important cattle disease anaplasmosis. Once infected, cattle remain lifelong carriers. Herein, we used flow cytometry to test the efficacy of three antimicrobials; oxytetracycline, imidocarb and enrofloxacin against Virginia (VGN) or Oklahoma (OK) A. marginale isolates in short-term erythrocyte cultures. Parasite viability was assessed using the vital dye hydroethidine (HE), which is detectable when living organisms convert HE to ethidium bromide. Viability of A. marginale in selected cultures was determined by subinoculation into susceptible calves. Data were analyzed by MANOVA, Tukey-Kramer honest significant difference and Wilcoxon rank sum tests. Receiver operating characteristic (ROC) analysis was used to correlate results with culture infectivity. Enrofloxacin inhibited A. marginale in a dose dependent manner. Surprisingly, higher concentrations of imidocarb were less effective than lower concentrations against A. marginale with significant differences (P < 0.05) observed between the two isolates. Oxytetracycline was the least active drug tested. Cultures infected with the OK isolate exposed to 4.0 microg/mL enrofloxacin and those of the VGN and OK isolates exposed to 1.0 microg/mL imidocarb were sterilized. This is the first in vitro study demonstrating the efficacy of enrofloxacin against A. marginale. Furthermore, these data indicate that flow cytometry is a useful assay for screening antimicrobials against A. marginale.

Anaplasma marginale↗
PubMed2005

Genetic diversity of Anaplasma marginale strains from cattle farms in the province of Palermo, Sicily.

Bovine anaplasmosis, caused by the tick-borne rickettsia Anaplasma marginale, is endemic in Sicily and results in economic loss to the cattle industry. This study was designed to characterize strains of A. marginale at the molecular level from cattle in the Province of Palermo, Sicily. Seropositivity of cattle >or=1 year old for A. marginale in the study area ranged from 62% to 100%. The observed prevalence of A. marginale infections in cattle herds ranged from 25% to 100%. Two predominant A. marginale msp4 genotypes were found. A positive correlation was found between the prevalence of infection and the presence of Rhipicephalus (Boophilus) annulatus. Phylogenetic analysis of msp4 sequences of European strains of A. marginale did not provide phylogeographical information. These results suggest that development of farm husbandry systems and vaccines for genetically heterogeneous populations of A. marginale are needed for control of anaplasmosis in this region of Sicily.

Anaplasma marginale↗
PubMed2006

Seroprevalence of Anaplasma phagocytophilum among healthy dogs and horses in Israel.

The presence of reacting antibodies to Anaplasma phagocytophilum has previously been demonstrated in Israel, both in humans and the golden jackal (Canis aureus syriacus). This study was undertaken to determine the seroprevalence of A. phagocytophilum antibodies in two additional potential hosts, domestic dogs and horses in order to investigate the possibility of exposure to the organism in Israel. Of 195 dogs tested, 9% were seroreactive with A. phagocytophilum antigen and 30% were seroreactive to Ehrlichia canis. Twenty-nine percent of the dogs seropositive for E. canis were also reactive to A. phagocytophilum. Two dogs had immunofluorescence antibody (IFA) antibody titres for A. phagocytophilum greater than E. canis. The equine serological survey (n = 300) revealed no seroreactive horses. The results presented in this study suggest that dogs in Israel could have been accidentally exposed to A. phagocytophilum, for example by ticks carried on migrating birds, however, the possibility of cross-reaction with E. canis should also be considered. In spite of the high prevalence of ticks on horses in Israel during the summer months, no evidence for exposure to A. phagocytophilum was apparent.

Anaplasma phagocytophilum↗
PubMed2006

Genetic characterization of Anaplasma (Ehrlichia) platys in dogs in Spain.

This paper reports the first genetic characterization of Anaplasma (Ehrlichia) platys in Spain from a naturally infected dog. The dog presented clinical signs compatible with canine ehrlichiosis. After DNA extraction and PCR amplification, 16S rRNA gene and citrate synthase gene ( gltA) of this agent were amplified. The GenBank accession number for the nucleotide sequence of the 16S rRNA gene of this strain is AY530806. The A. platys strains registered in France and Japan showed the highest similarity to the 16S rRNA gene sequence obtained from the Spanish strain. In the amplification of the gltA gene, a 1443 bp fragment was obtained, and three nucleotide differences were detected in comparison with other strains sequences. These data confirm the presence of A. platys in a dog showing clinical signs compatible with ehrlichiosis in Spain.

Anaplasma↗
PubMed2006

Phylogenetic analysis of Anaplasma marginale strains from Paraná State, Brazil, using the msp1alpha and msp4 genes.

Anaplasma marginale is an obligate intraerythrocytic rickettsial pathogen (order, Rickettsiales: family, Anaplasmataceae) that causes bovine anaplasmosis. This disease is widely distributed in tropical and sub-tropical regions of the world and causes important economic losses to cattle production. Major surface protein (MSP)1a (msp1alpha gene) is one of the six MSPs identified on A. marginale from cattle, whose sequence and size vary according to the number of tandem 28- to 29-amino acid repeats. This study characterized the msp1alpha and msp4 genes obtained from three distinct Brazilian herds from the State of Paraná. Three strains of the msp1alpha and one strain of the msp4 gene were sequenced. The strains evaluated revealed PCR products of different size, representing three, five and six internal repeats. Sequence analyses confirmed the number of tandem sequence copies and revealed a high degree of sequence identity with strains from other Brazilian States, as well as strains from the USA, Europe and Israel. The msp1alpha DNA and amino acid sequences from A. marginale and DNA sequences of msp4 strains did not reveal distinct phylogeographical segregation. However, the amino acid sequences of msp4 demonstrated definite phylogeographical relationship. These results suggest that the amino acid sequences of msp4 should be used for phylogenetic identification of A. marginale strains and may be an important tool for the epidemiology and control of anaplasmosis. Additionally, the close similarity of the Paraná strains of A. marginale with strains from USA, Europe and Asia may reflect the introduction of these genes during the development of the Brazilian bovine herd.

Amino Acid Sequence↗
PubMed2004

Anaplasma phagocytophilum AnkA binds to granulocyte DNA and nuclear proteins.

Human granulocytic anaplasmosis (HGA) is caused by the obligate intracellular bacterium Anaplasma phagocytophilum. The bacterium infects, survives, propagates in, and alters neutrophil phenotype, indicating unique survival mechanisms. AnkA is the only known A. phagocytophilum component that gains access beyond neutrophil vacuoles and is transported to the infected host cell nucleus. The ability of native and recombinant AnkA to bind DNA and nuclear proteins from host HL-60 cells was assessed by the use of immunoprecipitation after cis-diamminedichloroplatinum (cis-DDP) DNA-protein crosslinking, by probing uninfected HL-60 cell nuclear lysates for AnkA binding, and by recovery and sequence analysis of immunoprecipitated DNA. AnkA binds HL-60 cell DNA as well as nuclear proteins of approximately 86, 53 and 25 kDa, whereas recombinant A. phagocytophilum Msp2 or control proteins do not. DNA immunoprecipitation reveals AnkA binding to a variety of target genes in the human genome, including genes that encode proteins with ATPase, tyrosine phosphatase and NADH dehydrogenase-like functions. These data indicate that AnkA could exert some effect on cells through binding to protein:DNA complexes in neutrophil nuclei. Whether AnkA binding leads to neutrophil functional alterations, and how such alterations might occur will depend upon definitive identification of binding partners and associated metabolic and biochemical pathways.

Adenosine Triphosphatases↗
PubMed2005

Anaplasma phagocytophilum inhibits human neutrophil apoptosis via upregulation of bfl-1, maintenance of mitochondrial membrane potential and prevention of caspase 3 activation.

The inhibition of neutrophil apoptosis plays a central role in human granulocytic anaplasmosis. Intracellular signalling pathways through which the obligatory intracellular bacterium Anaplasma phagocytophilum inhibits the spontaneous apoptosis of human peripheral blood neutrophils were investigated. bfl-1 mRNA levels in uninfected neutrophils after 12 h in culture were reduced to approximately 5-25% of 0 h levels, but remained high in infected neutrophils. The eukaryotic RNA synthesis inhibitor, actinomycin D, prevented the maintenance of bfl-1 mRNA levels by A. phagocytophilum. Differences in mcl-1, bax, bcl-w, bad or bak mRNA levels in infected versus uninfected neutrophils were not remarkable. By using mitochondrial fluorescent dyes, Mitotracker Red and JC-1, it was found that most uninfected neutrophils lost mitochondrial membrane potential after 10-12 h incubation, whereas A. phagocytophilum-infected neutrophils maintained high membrane potential. Caspase 3 activity and the degree of apoptosis were lower in dose-dependent manner in A. phagocytophilum-infected neutrophils at 16 h post infection, as compared to uninfected neutrophils. Anti-active caspase 3 antibody labelling showed less positively stained population in infected neutrophils compared to those in uninfected neutrophils after 12 h incubation. These results suggest that A. phagocytophilum inhibits human neutrophil apoptosis via transcriptional upregulation of bfl-1 and inhibition of mitochondria-mediated activation of caspase 3.

Anaplasma phagocytophilum↗
PubMed2005

Gene expression profiling of human promyelocytic cells in response to infection with Anaplasma phagocytophilum.

Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae) causes human, equine and canine granulocytic anaplasmosis and tick-borne fever of ruminants. The rickettsia parasitizes granulocytes and bone marrow progenitor cells, and can be propagated in human promyelocytic and tick cell lines. In this study, microarrays of synthetic polynucleotides of 21,329 human genes were used to identify genes that are differentially expressed in HL-60 human promyelocytic cells in response to infection with A. phagocytophilum. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) of selected genes confirmed the results of the microarray analysis. Six genes in the A. phagocytophilum-infected cells were found to be upregulated greater than 30-fold, while expression of downregulated genes most often did not change more than sixfold. Genes that were found to be differentially regulated in infected cells were those essential for cellular mechanisms including growth and differentiation, cell transport, signalling and communication and protective response against infection, some of which are most likely necessary for infection and multiplication of A. phagocytophilum in host cells. The differentially regulated genes described herein provide new information on the gene expression profiles in A. phagocytophilum-infected HL-60 cells, thus expanding in a global manner the existing information on the response of mammalian cells to A. phagocytophilum infection.

Anaplasma phagocytophilum↗