Publications (18) View all
-
Article: Antigen variability in Anaplasma phagocytophilum during chronic infection of a reservoir host.
[show abstract] [hide abstract]
ABSTRACT: Anaplasma phagocytophilum is an obligately intracellular, tick-transmitted, bacterial pathogen of humans and other animals. In order to evade host immunity during the course of infection, A. phagocytophilum utilizes gene conversion to shuffle approximately 100 functional pseudogenes into a single expression cassette of the msp2(p44) gene, which encodes the major surface antigen, major surface protein 2 (Msp2). The role and extent of msp2(p44) recombination in a reservoir host for A. phagocytophilum have not been evaluated. In the current study, we explored patterns of recombination and expression site variability of the msp2(p44) gene in three chronically infected woodrats, a reservoir for the disease in the Western USA. All three woodrats developed persistent infection of at least 6 months duration; two of them maintained active infection for at least 8 months. In total, we detected the emergence of 60 unique msp2(p44) expression site variants with no common temporal patterns of expression site recombination among the three A. phagocytophilum populations. Both the strength of infection (i.e. pathogen load) and the genetic diversity of pseudogenes detected at the msp2(p44) expression site fluctuated periodically during the course of infection. An analysis of the genomic pseudogene exhaustion rate showed that the repertoire of pseudogenes available to the A. phagocytophilum population could in theory become depleted within a year. However, the apparent emergence of variant pseudogenes suggests that the pathogen could potentially evade host immunity indefinitely. Our findings suggest a tightly co-evolved relationship between A. phagocytophilum and woodrats in which the pathogen perpetually evades host immunity yet causes no detectable disease.Microbiology 08/2012; 158(Pt 10):2632-41. · 3.06 Impact Factor -
Article: Evolution of antigen variation in the tick-borne pathogen Anaplasma phagocytophilum.
[show abstract] [hide abstract]
ABSTRACT: Anaplasma phagocytophilum is an obligately intracellular tick-transmitted bacterial pathogen of humans and other animals. During the course of infection, A. phagocytophilum utilizes gene conversion to shuffle ∼100 functional pseudogenes into a single expression cassette of the msp2(p44) gene, which codes for the major surface antigen and major surface protein 2 (MSP2). The role and extent of msp2(p44) recombination, particularly in hosts that only experience acute infections, is not clear. In the present study, we explored patterns of recombination and expression of the msp2(p44) gene of A. phagocytophilum in a serially infected mouse model. Even though the bacterium was passed rapidly among mice, minimizing the opportunities for the host to develop adaptive immunity, we detected the emergence of 34 unique msp2(p44) expression cassette variants. The expression of msp2(p44) pseudogenes did not follow a consistent pattern among different groups of mice, although some pseudogenes were expressed more frequently than others. In addition, among 263 expressed pseudogenes, 3 mosaic sequences each consisting of 2 different pseudogenes were identified. Population genetic analysis showed that genetic diversity and subpopulation differentiation tended to increase over time until stationarity was reached but that the variance that was observed in allele (expressed pseudogene) frequency could occur by drift alone only if a high variance in bacterial reproduction could be assumed. These findings suggest that evolutionary forces influencing antigen variation in A. phagocytophilum may comprise random genetic drift as well as some innate but apparently nonpurifying selection prior to the strong frequency-dependent selection that occurs cyclically after hosts develop strong adaptive immunity.Molecular Biology and Evolution 09/2011; 29(1):391-400. · 5.55 Impact Factor -
Article: Molecular characterization reveals distinct genospecies of Anaplasma phagocytophilum from diverse North American hosts.
[show abstract] [hide abstract]
ABSTRACT: Anaplasma phagocytophilum is an emerging tick-borne pathogen that infects humans, domestic animals and wildlife throughout the Holarctic. In the far-western United States, multiple rodent species have been implicated as natural reservoirs for A. phagocytophilum. However, the presence of multiple A. phagocytophilum strains has made it difficult to determine which reservoir hosts pose the greatest risk to humans and domestic animals. Here we characterized three genetic markers (23S-5S rRNA intergenic spacer, ank and groESL) from 73 real-time TaqMan PCR-positive A. phagocytophilum strains infecting multiple rodent and reptile species, as well as a dog and a horse, from California. Bayesian and maximum-likelihood phylogenetic analyses of all three genetic markers consistently identified two major clades, one of which consisted of A. phagocytophilum strains infecting woodrats and the other consisting of strains infecting sciurids (chipmunks and squirrels) as well as the dog and horse strains. In addition, analysis of the 23S-5S rRNA spacer region identified two unique and highly dissimilar clades of A. phagocytophilum strains infecting several lizard species. Our findings indicate that multiple unique strains of A. phagocytophilum with distinct host tropisms exist in California. Future epidemiological studies evaluating human and domestic animal risk should incorporate these distinctions.Journal of Medical Microbiology 09/2011; 61(Pt 2):204-12. · 2.50 Impact Factor -
Article: Temporal patterns of tick-borne granulocytic anaplasmosis in California.
[show abstract] [hide abstract]
ABSTRACT: Granulocytic anaplasmosis (GA) is a tick-borne emerging infectious disease caused by the bacterium Anaplasma phagocytophilum. From fall 2005 to spring 2007, A. phagocytophilum infection prevalence in small mammals and tick abundance were monitored at 4 study sites in coastal California. The abundance of different life stages of questing Ixodes pacificus ticks fluctuated seasonally with the number of adults peaking December to February, nymphs peaking May to July, and larvae peaking April to June. Numerous Ixodes tick species were found attached to dusky-footed woodrats (Neotoma fuscipes), chimunks (Tamias spp.), and deer mice (Peromyscus maniculatus); however, attached tick larvae on all 3 rodent species were primarily I. pacificus, attached nymphs were primarily I. angustus, and adults were either I. ochotonae, I. spinipalpis, or I. woodi. A. phagocytophilum DNA was detected by PCR in 2.2% (n=275, 95% C.I.=0.09-4.9) of sampled ticks. The overall A. phagocytophilum seroprevalence among small mammals was 7.4% (n=654, 95% C.I.=5.5-9.7) while 7.2% (n=125, 95% C.I.=3.5-13.4) of the animals were found to be PCR-positive. Seropositive animals included woodrats, chipmunks, and deer mice, although only woodrats and chipmunks had PCR-detectable infections. Seroprevalence varied temporally among species with the majority of exposed deer mice detected in fall 2006 and the majority of exposed woodrats and chipmunks identified in spring 2007. This study highlights the importance of multiple-year monitoring of both vectors and wildlife hosts in order to better understand the complex ecology of A. phagocytophilum and other related tick-borne disease agents.Ticks and Tick-borne Diseases 06/2011; 2(2):81-7. -
Article: Nidicolous ticks of small mammals in Anaplasma phagocytophilum-enzootic sites in northern California.
[show abstract] [hide abstract]
ABSTRACT: Ixodes spp. tick-borne zoonotic diseases are present across the Holarctic in humans, domestic animals, and wildlife. Small mammals are reservoirs for the rickettsial pathogen Anaplasma phagocytophilum and tick vectors may include catholic-feeding bridge vectors as well as host-specialist or nidicolous ticks. Far western North American communities in which A. phagocytophilum is maintained are complex ecologically, with multiple reservoir host and tick species, multiple strains of the bacterial pathogen A. phagocytophilum and differences in dynamics of hosts and vectors across heterogeneous landscapes. We evaluated sites in northern California in order to identify primarily nidicolous ticks and the hosts they infest. A total of 667 ticks was found in 11 study sites, including 288 on flags and 379 attached to small mammals. Larvae were over-represented among attached ticks and adults on flags. The most abundant species was I. pacificus. Two-hundred fourteen nidicolous ticks were found, most abundantly I. angustus and I. spinipalpis. All adult I. ochotonae, I. auritulus, I. angustus, I. jellisoni, and I. woodi were female, while the male:female ratio of I. spinipalpis was 1.2:1 and 1:1 for I. pacificus. The greatest number of ticks was obtained from Tamias ochrogenys, Peromyscus spp., and Neotoma fuscipes. Of 234 small mammal individuals that were infested with Ixodes spp., only 81 (34.6%) were infested with I. pacificus. The remaining infested small mammals hosted nidicolous tick species. Eight ticks were PCR-positive, including 6 I. pacificus (one adult, one larva, and 6 nymphs), and 2 adult I. ochotonae and high PCR prevalences of 18% and 9% were detected in woodrats and chipmunks, respectively. Nymphal I. angustus ticks were active year-long with a possible increase in August while larval activity was only observed in December and spring months and adults only during spring and fall. Overall, we show high tick species richness and year-round high levels of infestation on rodents by several different nidicolous ticks in areas where A. phagocytophilum is enzootic, including on reported reservoir species.Ticks and Tick-borne Diseases 06/2011; 2(2):75-80.
