Genetic Diversity of
            <i>Borrelia burgdorferi</i>
            Sensu Stricto in
            <i>Peromyscus leucopus</i>
            , the Primary Reservoir of Lyme Disease in a Region of Endemicity in Southern Maryland

Anderson, Jennifer M.; Norris, Douglas E.

doi:10.1128/aem.00014-06

Cited by 36 publications

(37 citation statements)

References 73 publications

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“…Thus, one explanation is that the richness of B. garinii ospC strains in birds is higher than the richness of B. afzelii ospC strains in rodents. To date, most of the studies investigating ospC strain richness in vertebrate reservoir hosts have focused on mammals (1,13,50,52,55,66,82,83). The two studies that investigated birds (81,85) found a mean ospC strain richness (1.00 to 1.76 strains per tick) that was low compared to that found in the studies with mammals, but this could be an artifact of the relatively inefficient molecular methods that were used in the bird studies (RLB assay and Sanger sequencing).…”

Section: Cross-immunity and Co-occurrence Of Borrelia Ospc Strainsmentioning

confidence: 77%

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Cross-Immunity and Community Structure of a Multiple-Strain Pathogen in the Tick Vector

Durand

Jacquet

Paillard

et al. 2015

Appl Environ Microbiol

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bMany vector-borne pathogens consist of multiple strains that circulate in both the vertebrate host and the arthropod vector. Characterization of the community of pathogen strains in the arthropod vector is therefore important for understanding the epidemiology of mixed vector-borne infections. Borrelia afzelii and B. garinii are two species of tick-borne bacteria that cause Lyme disease in humans. These two sympatric pathogens use the same tick, Ixodes ricinus, but are adapted to different classes of vertebrate hosts. Both Borrelia species consist of multiple strains that are classified using the highly polymorphic ospC gene. Vertebrate cross-immunity against the OspC antigen is predicted to structure the community of multiple-strain Borrelia pathogens. Borrelia isolates were cultured from field-collected I. ricinus ticks over a period spanning 11 years. The Borrelia species of each isolate was identified using a reverse line blot (RLB) assay. Deep sequencing was used to characterize the ospC communities of 190 B. afzelii isolates and 193 B. garinii isolates. Infections with multiple ospC strains were common in ticks, but vertebrate cross-immunity did not influence the strain structure in the tick vector. The pattern of genetic variation at the ospC locus suggested that vertebrate cross-immunity exerts strong selection against intermediately divergent ospC alleles. Deep sequencing found that more than 50% of our isolates contained exotic ospC alleles derived from other Borrelia species. Two alternative explanations for these exotic ospC alleles are cryptic coinfections that were not detected by the RLB assay or horizontal transfer of the ospC gene between Borrelia species. Many vector-borne pathogens consist of multiple genetically distinct strains (1-4). The adaptive arm of the vertebrate immune system plays a key role in generating and maintaining this diversity of pathogen strains (5-7). Genetic diversity is often the highest at loci coding for surface-exposed pathogen molecules that function during the invasion and infection of host tissues (8, 9). The study of these highly polymorphic pathogen molecules is important for understanding how cross-reactive acquired immunity can mediate indirect competition and superinfection in the vertebrate host (10, 11). In addition, these pathogen outer surface proteins are often used to characterize pathogen strains because they provide an upper estimate of pathogen strain richness.In vector-borne diseases, the community of pathogen strains can be studied in both the vertebrate host and the arthropod vector. The vertebrate immune system creates nonrandom associations between pathogen strains (1, 12) that are subsequently transmitted to the arthropod vector. Conversely, the study of mixed infections in the arthropod vector can provide information on the processes that structure the community of multiple pathogen strains in the vertebrate host (13,14). In addition, estimates of strain richness in the arthropod vector are important for understanding the frequency with which ...

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Section: Cross-immunity and Co-occurrence Of Borrelia Ospc Strainsmentioning

confidence: 77%

“…Several papers have dealt with the nomenclature of the major ospC groups in B. burgdorferi sensu lato (46,47,49,54,65,66). In the United States, workers have developed a wellestablished system of names for the major ospC groups of B. burgdorferi sensu stricto (45).…”

Section: Methodsmentioning

confidence: 99%

Cross-Immunity and Community Structure of a Multiple-Strain Pathogen in the Tick Vector

Durand

Jacquet

Paillard

et al. 2015

Appl Environ Microbiol

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“…This laboratory observation is compatible with what is observed in the environment and in the clinic. Although experimental studies on B. burgdorferi are frequently carried out using a single strain, field studies have shown that mixed infections with different B. burgdorferi genotypes occur in ticks and mammalian reservoir hosts (46)(47)(48)(49). In humans, different strains have been isolated from individual Lyme disease patients (50,51).…”

Section: Discussionmentioning

confidence: 99%

Understanding Barriers to Borrelia burgdorferi Dissemination during Infection Using Massively Parallel Sequencing

Troy

Lin²,

Gao³

et al. 2013

Infect Immun

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dBorrelia burgdorferi is an invasive spirochete that can cause acute and chronic infections in the skin, heart, joints, and central nervous system of infected mammalian hosts. Little is understood about where the bacteria encounter the strongest barriers to infection and how different components of the host immune system influence the population as the infection progresses. To identify population bottlenecks in a murine host, we utilized Tn-seq to monitor the composition of mixed populations of B. burgdorferi during infection. Both wild-type mice and mice lacking the Toll-like receptor adapter molecule MyD88 were infected with a pool of infectious B. burgdorferi transposon mutants with insertions in the same gene. At multiple time points postinfection, bacteria were isolated from the mice and the compositions of the B. burgdorferi populations at the injection site and in distal tissues determined. We identified a population bottleneck at the site of infection that significantly altered the composition of the population. The magnitude of this bottleneck was reduced in MyD88 ؊/؊ mice, indicating a role for innate immunity in limiting early establishment of B. burgdorferi infection. There is not a significant bottleneck during the colonization of distal tissues, suggesting that founder effects are limited and there is not a strict limitation on the number of organisms able to initiate populations at distal sites. These findings further our understanding of the interactions between B. burgdorferi and its murine host in the establishment of infection and dissemination of the organism.

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“…Borrelia isolates from small mammals in the field contain highly heterogeneous (both genetically and phenotypically) populations of borreliae, and as demonstrated in this study, following long-term storage of this B. bissettii isolate immunocompetent animals were capable of clearing spirochaetes after needle challenge. However, passage through SCID mice allowed us to select for host-adapted infectious populations of the spirochaete that were subsequently able to infect immunocompetent animals (Anderson & Norris, 2006;Hofmeister et al, 1999). B. bissettii infection results in similar bacterial burdens as B. burgdorferi ss in skin, heart and bladder tissues, but lower burdens in joint tissues Bacterial burdens were determined by qPCR to compare the ability of B. bissettii and B. burgdorferi ss to disseminate throughout and be retained in the tissues of infected animals.…”

Section: B Bissettii Is Able To Infect Immunocompetent Mice Only Aftmentioning

confidence: 99%

Similarities in murine infection and immune response to Borrelia bissettii and Borrelia burgdorferi sensu stricto

Leydet

Liang

2015

Microbiology

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In 1982, Borrelia burgdorferi sensu stricto (ss) was identified as the aetiological agent of Lyme disease. Since then an increasing number of Borrelia burgdorferi sensu lato (sl) species have been isolated in the United States. To date, many of these species remain understudied despite mounting evidence associating them with human illness. Borrelia bissettii is a spirochaete closely related to B. burgdorferi that has been loosely associated with human illness. Using an experimental murine infection model, we compared the infectivity and humoral immune response with a North American isolate of B. bissettii and B. burgdorferi using culture, molecular and serological methods. The original B. bissettii cultures were unable to infect immunocompetent mice, but were confirmed to be infectious after adaptation in immunodeficient animals. B. bissettii infection resulted in spirochaete burdens similar to B. burgdorferi in skin, heart and bladder whereas significantly lower burdens were observed in the joint tissues. B. bissettii induced an antibody response similar to B. burgdorferi as measured by both immunoblotting and the C6 ELISA. Additionally, this isolate of B. bissettii was sequenced on the Ion Torrent PGM, which successfully identified many genes orthologous to mammalian virulence factors described in B. burgdorferi. Similarities seen between both infections in this well-characterized murine model contribute to our understanding of the potential pathogenic nature of B. bissettii. Infection dynamics of B. bissettii, and especially the induced humoral response, are similar to B. burgdorferi, suggesting this species may contribute to the epidemiology of human borreliosis. INTRODUCTIONIn 1982, the causative agent of Lyme disease was isolated from an Ixodes scapularis tick (Burgdorfer et al., 1982). The bacterium, a spirochaete, was named Borrelia burgdorferi after Willy Burgdorfer, one of the researchers who identified it. Three decades after this discovery, advancements in molecular biology have led to the delineation of the B. burgdorferi sensu lato (sl) species complex (Stanek & Reiter, 2011). This complex comprises, at the time of writing, 18 named species distributed around the globe (Kurtenbach et al., 2006;Margos et al., 2011). While genetically similar, many of these bacteria occur in specific tick-vertebrate enzootic cycles (Gray et al., 2002). Some vector ticks commonly contact humans (Estrada-Peña & Jongejan, 1999), but many of these Borrelia enzootic cycles involve ticks that rarely bite humans, which subsequently leaves the pathogenicity of many B. burgdorferi sl species in question (Kiewra & Lonc, 2012;Margos et al., 2012).In 2011, 33 000 cases of human Lyme disease were reported to the Centers for Disease Control (CDC, 2011). Yet, recently the CDC has announced they estimate this statistic is well below the actual number of diagnosed cases (*300 000 year) (Hinckley et al., 2014). Although seven B. burgdorferi sl species have been isolated in culture in North America only B. burgdorferi sensu stricto (...

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Genetic Diversity of Borrelia burgdorferi Sensu Stricto in Peromyscus leucopus , the Primary Reservoir of Lyme Disease in a Region of Endemicity in Southern Maryland

Cited by 36 publications

References 73 publications

Cross-Immunity and Community Structure of a Multiple-Strain Pathogen in the Tick Vector

Cross-Immunity and Community Structure of a Multiple-Strain Pathogen in the Tick Vector

Understanding Barriers to Borrelia burgdorferi Dissemination during Infection Using Massively Parallel Sequencing

Similarities in murine infection and immune response to Borrelia bissettii and Borrelia burgdorferi sensu stricto

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