Quantitative Differences in Salivary Pathogen Load during Tick Transmission Underlie Strain-Specific Variation in Transmission Efficiency of<i>Anaplasma marginale</i>

Ueti, Massaro W.; Knowles, Donald P.; Davitt, Christine M.; Scoles, Glen A.; Baszler, Timothy V.; Palmer, Guy H.

doi:10.1128/iai.01164-08

Cited by 47 publications

(67 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although I. scapularis hemolymph is poorly borreliacidal (76), elimination of spirochetes by cellular innate defenses within the hemocoel, shown herein by us and others (15), may further limit the number of organisms that reach their salivary gland target. Because salivary glands are a well-recognized anatomical barrier for vector-borne pathogens (6,(77)(78)(79), it is also plausible that this organ impedes the migration of B. burgdorferi. Along these lines, our visualization of spirochetes in association with the acinar surface as well as with multiple intraglandular structures raises the possibility that, as postulated for the midgut, the salivary glands comprise a succession of obstacles that the spirochete must negotiate via a multistep process in order to attain its goal of accessing the salivary stream.…”

Section: Figurementioning

confidence: 99%

Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks

et al. 2009

View full text Add to dashboard Cite

Lyme disease is caused by transmission of the spirochete Borrelia burgdorferi from ticks to humans. Although much is known about B. burgdorferi replication, the routes and mechanisms by which it disseminates within the tick remain unclear. To better understand this process, we imaged live, infectious B. burgdorferi expressing a stably integrated, constitutively expressed GFP reporter. Using isolated tick midguts and salivary glands, we observed B. burgdorferi progress through the feeding tick via what we believe to be a novel, biphasic mode of dissemination. In the first phase, replicating spirochetes, positioned at varying depths throughout the midgut at the onset of feeding, formed networks of nonmotile organisms that advanced toward the basolateral surface of the epithelium while adhering to differentiating, hypertrophying, and detaching epithelial cells. In the second phase of dissemination, the nonmotile spirochetes transitioned into motile organisms that penetrated the basement membrane and entered the hemocoel, then migrated to and entered the salivary glands. We designated the first phase of dissemination "adherence-mediated migration" and provided evidence that it involves the inhibition of spirochete motility by one or more diffusible factors elaborated by the feeding tick midgut. Our studies, which we believe are the first to relate the transmission dynamics of spirochetes to the complex morphological and developmental changes that the midgut and salivary glands undergo during engorgement, challenge the conventional viewpoint that dissemination of Lyme disease-causing spirochetes within ticks is exclusively motility driven.

show abstract

Section: Figurementioning

confidence: 99%

Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks

et al. 2009

View full text Add to dashboard Cite

show abstract

“…The numbers of organisms in the salivary gland and saliva at the time of transmission are 10-fold and 30-fold less, respectively, than the numbers of organisms in a high-transmission-efficiency strain (25). Transmission is correspondingly less efficient and requires Ͼ30-fold more ticks (9,25). This statistically and biologically significant transmission phenotype provides a model for linking gene content and expression with transmission efficiency.…”

mentioning

confidence: 99%

“…For example, cholera pandemics are associated with a limited diversity of related, highly transmissible Vibrio cholerae strains (4). For vectorborne pathogens, efficient transmission is also dictated by infection and replication within the arthropod host (10,15,25,26). While the basic cycle of development within the arthropod vector has been identified for many important pathogens, including Anaplasma, Borrelia, Plasmodium, Rickettsia, and Trypanosoma, the critical microbial determinants of transmission efficiency in the vector remain unknown for most bacterial and protozoan pathogens.…”

mentioning

confidence: 99%

Association of Pathogen Strain-Specific Gene Transcription and Transmission Efficiency Phenotype of Anaplasma marginale

Agnes

Herndon²,

Ueti³

et al. 2010

Infect Immun

Self Cite

View full text Add to dashboard Cite

Efficient transmission of pathogens by an arthropod vector is influenced by the ability of the pathogen to replicate and develop infectiousness within the arthropod host. While the basic life cycle of development within and transmission from the arthropod vector are known for many bacterial and protozoan pathogens, the determinants of transmission efficiency are largely unknown and represent a significant gap in our knowledge. The St. Maries strain of Anaplasma marginale is a high-transmission-efficiency strain that replicates to a high titer in the tick salivary gland and can be transmitted by <10 ticks. In contrast, A. marginale subsp. centrale (Israel vaccine strain) has an identical life cycle but replicates to a significantly lower level in the salivary gland, with transmission requiring >30-fold more ticks. We hypothesized that strain-specific genes expressed in the tick salivary gland at the time of transmission are linked to the differences in the transmission efficiency phenotype. Using both annotation-dependent and -independent analyses of the complete genome sequences, we identified 58 strain-specific genes. These genes most likely represent divergence from common ancestral genes in one or both strains based on analysis of synteny and lack of statistical support for acquisition as islands by lateral gene transfer. Twenty of the St. Maries strain-specific genes and 16 of the strain-specific genes in the Israel strain were transcribed in the tick salivary gland at the time of transmission. Although associated with the transmission phenotype, the expression levels of strain-specific genes were equal to or less than the expression levels in infected erythrocytes in the mammalian host, suggesting that function is not limited to salivary gland colonization.Transmission efficiency is a primary determinant of pathogen prevalence. Strain-specific differences in transmission efficiency underlie the strain structure in the host population and the patterns of infection and disease. For example, cholera pandemics are associated with a limited diversity of related, highly transmissible Vibrio cholerae strains (4). For vectorborne pathogens, efficient transmission is also dictated by infection and replication within the arthropod host (10,15,25,26). While the basic cycle of development within the arthropod vector has been identified for many important pathogens, including Anaplasma, Borrelia, Plasmodium, Rickettsia, and Trypanosoma, the critical microbial determinants of transmission efficiency in the vector remain unknown for most bacterial and protozoan pathogens.Transmission of Anaplasma spp. is initiated when ixodid ticks ingest an infected blood meal during acquisition feeding on a bacteremic mammalian host (25, 26). The organisms then replicate within the midgut epithelium, invade the salivary gland, and, concomitant with attachment and feeding on a naïve host, undergo a second round of replication and are released into the saliva for transmission (13,25,26). Importantly, the efficiencies of this developmental...

show abstract

“…centrale vaccine strain was thought for a long time not to be transmitted by most ticks, it was shown that, in fact, it colonized the tick well but was not secreted into the tick saliva in sufficient quantities for robust transmission (23,24). Dramatically increasing tick numbers in transmission experiments overcame the transmission barrier (25). Is the reduced ability of the A. marginale subsp.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Anaplasma marginale subsp. centrale Strains by Use of msp1aS Genotyping Reveals a Wildlife Reservoir

et al. 2016

View full text Add to dashboard Cite

Bovine anaplasmosis caused by the intraerythrocytic rickettsial pathogen Anaplasma marginale is endemic in South Africa. Anaplasma marginale subspecies centrale also infects cattle; however, it causes a milder form of anaplasmosis and is used as a live vaccine against A. marginale. There has been less interest in the epidemiology of A. marginale subsp. centrale, and, as a result, there are few reports detecting natural infections of this organism. When detected in cattle, it is often assumed that it is due to vaccination, and in most cases, it is reported as coinfection with A. marginale without characterization of the strain. A total of 380 blood samples from wild ruminant species and cattle collected from biobanks, national parks, and other regions of South Africa were used in duplex real-time PCR assays to simultaneously detect A. marginale and A. marginale subsp. centrale. PCR results indicated high occurrence of A. marginale subsp. centrale infections, ranging from 25 to 100% in national parks. Samples positive for A. marginale subsp. centrale were further characterized using the msp1aS gene, a homolog of msp1␣ of A. marginale, which contains repeats at the 5= ends that are useful for genotyping strains. A total of 47 Msp1aS repeats were identified, which corresponded to 32 A. marginale subsp. centrale genotypes detected in cattle, buffalo, and wildebeest. RepeatAnalyzer was used to examine strain diversity. Our results demonstrate a diversity of A. marginale subsp. centrale strains from cattle and wildlife hosts from South Africa and indicate the utility of msp1aS as a genotypic marker for A. marginale subsp. centrale strain diversity. Bovine anaplasmosis (gallsickness) is a tick-borne disease caused by the intraerythrocytic rickettsial pathogen Anaplasma marginale (1). A. marginale is globally prevalent and results in anemia, with mortality rates of up to 30% (2). Anaplasma marginale subspecies centrale is a less virulent subspecies detected by Sir Arnold Theiler, who recognized its potential as a vaccine against anaplasmosis; 100 years later this live vaccine is still in use in South Africa, Israel, South America, and Australia (3, 4). The strain that is used as a vaccine originated from Theiler's original isolation and was exported at various times to other countries where it has been propagated in the laboratory; the strain known as the "Israel strain" or the "vaccine strain" was sent to Israel in the 1950s and was used to generate the complete genome sequence for A. marginale subsp. centrale in 2010 (5). A. marginale subsp. centrale does not provide complete protection against A. marginale infection but does protect against severe anaplasmosis (6, 7). (8)(9)(10)(11). Cattle are naturally susceptible to A. marginale (4). There has not been much interest in the epidemiology of A. marginale subsp. centrale, with few reports detecting natural infections of this organism; most often, when detected in cattle it is assumed that it is due to vaccination and is reported as coinfection with A. marginale without...

show abstract

Quantitative Differences in Salivary Pathogen Load during Tick Transmission Underlie Strain-Specific Variation in Transmission Efficiency ofAnaplasma marginale

Cited by 47 publications

References 30 publications

Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks

Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks

Association of Pathogen Strain-Specific Gene Transcription and Transmission Efficiency Phenotype of Anaplasma marginale

Characterization of Anaplasma marginale subsp. centrale Strains by Use of msp1aS Genotyping Reveals a Wildlife Reservoir

Contact Info

Product

Resources

About