Immunization with Outer Surface Protein (Osp) A, but Not OspC, Provides Cross-Protection of Mice Challenged with North American Isolates of Borrelia burgdorferi

Probert, William S.; Crawford, Melissa; Cadiz, Renante B.; Lefebvre, Rance B

doi:10.1093/infdis/175.2.400

Cited by 105 publications

(95 citation statements)

References 51 publications

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“…As previously noted in California, 16 several of the Oregon B. burgdorferi isolates had truncated forms of OspB. Variation in antibody reactivity to OspCs has been previously reported 17,18 and undoubtedly explains our results in which only 14 of 16 B. burgdorferi isolates from Oregon were recognized by the anti-OspC MAb. Like the California isolates of B. burgdorferi, 16 variability in the amount of OspC expressed among the Oregon isolates was noted.…”

Section: Discussionsupporting

confidence: 83%

Isolation of Borrelia burgdorferi from Neotoma fuscipes, Peromyscus maniculatus, Peromyscus boylii, and Ixodes pacificus in Oregon.

Burkot¹,

Clover²,

Happ³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. The number of Lyme disease cases in Oregon has increased in recent years despite the fact that the pathogen, Borrelia burgdorferi, has never been isolated in the state. Rodent and tick surveys were undertaken in 1997 to isolate and characterize strains of B. burgdorferi from Oregon and to identify potential reservoirs and vectors of Lyme disease. Borrelia burgdorferi was isolated from Neotoma fuscipes, Peromyscus maniculatus, P. boylii, and Ixodes pacificus. Both N. fuscipes and P. maniculatus were infested with I. pacificus and I. spinipalpis. Although I. pacificus infested P. boylii, I. spinipalpis was not found on this rodent, and only 4% of the P. boylii were infected with B. burgdorferi compared with the 19% and 18% infection rates found in N. fuscipes and P. maniculatus, respectively. Variation in the molecular weights of the outer surface proteins A and B were found in these first confirmed isolates of B. burgdorferi from Oregon, as well as truncated forms of outer surface protein B.Lyme disease caused by Borrelia burgdorferi is the most common vector-borne disease in the United States. Since the discovery of the etiologic agent in 1981, the known endemic range of Lyme disease together with the numbers of reported cases has steadily increased. 1 The principal vectors of B. burgdorferi are Ixodes scapularis and I. pacificus in the eastern and western United States, respectively. 2 Recently, I. spinipalpis was found to be a competent Lyme disease vector in enzootic cycles involving mice (Peromyscus spp) and wood rats (Neotoma fuscipes) in California, 3 and N. mexicana in Colorado. 4 Despite reports of I. spinipalpis attaching to humans in Oregon, 5 New Mexico (Centers for Disease Control and Prevention [CDC], unpublished data), and Canada, 6 I. spinipalpis is not believed to be important in the transmission of B. burgdorferi to humans since nymphs are usually found either attached to animals or in the more humid environment of a rodent nest.Reports of Lyme disease cases have been increasing in number and spreading in geographic range in the Pacific Northwest. In Oregon, there were only four reported cases of Lyme disease from two counties in 1991 (CDC, unpublished data) compared with 19 cases from 11 counties reported in 1996. 7 Although spirochetes were found in almost 2% of I. pacificus in Oregon from 1982 to 1984, these spirochetes were not identified. 8 The results of a survey undertaken in April-May 1997 to try to confirm the presence of B. burgdorferi in Oregon and to ascertain which animals and ticks may be responsible for the maintenance of this human pathogen in enzootic cycles are presented. MATERIALS AND METHODSField studies. Field studies in southern Oregon were undertaken during 1997 at two sites in Jackson County (Woodrat Mountain and Lost Creek) and one site (Spencer Creek) in Josephine County. Host-seeking adult I. pacificus ticks were collected by flagging vegetation during April 1997 and held at 4ЊC in a saturated humidity until processed for spirochete isolation in Barbour-Stoen...

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Section: Discussionsupporting

confidence: 83%

Isolation of Borrelia burgdorferi from Neotoma fuscipes, Peromyscus maniculatus, Peromyscus boylii, and Ixodes pacificus in Oregon.

Burkot¹,

Clover²,

Happ³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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“…Antibody responses to OspC are largely strain-specific, but responses to other outer surface proteins (e.g. OspA) are cross-reactive, so there is scope for antibody-mediated competition between strains [36]. Borrelia spirochaetes respond adaptively to nutrient deprivation, suggesting that availability of nutrients may sometimes be a limiting factor for their replication [37].…”

Section: Discussionmentioning

confidence: 99%

Within-host competition betweenBorrelia afzelii ospCstrains in wild hosts as revealed by massively parallel amplicon sequencing

Strandh

Råberg

2015

Phil. Trans. R. Soc. B

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Infections frequently consist of more than one strain of a given pathogen. Experiments have shown that co-infecting strains often compete, so that the infection intensity of each strain in mixed infections is lower than in single strain infections. Such within-host competition can have important epidemiological and evolutionary consequences. However, the extent of competition has rarely been investigated in wild, naturally infected hosts, where there is noise in the form of varying inoculation doses, asynchronous infections and host heterogeneity, which can potentially alleviate or eliminate competition. Here, we investigated the extent of competition between Borrelia afzelii strains (as determined by ospC genotype) in three host species sampled in the wild. For this purpose, we developed a protocol for 454 amplicon sequencing of ospC , which allows both detection and quantification of each individual strain in an infection. Each host individual was infected with one to six ospC strains. The infection intensity of each strain was lower in mixed infections than in single ones, showing that there was competition. Rank-abundance plots revealed that there was typically one dominant strain, but that the evenness of the relative infection intensity of the different strains in an infection increased with the multiplicity of infection. We conclude that within-host competition can play an important role under natural conditions despite many potential sources of noise, and that quantification by next-generation amplicon sequencing offers new possibilities to dissect within-host interactions in naturally infected hosts.

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“…It can cause a strong immunoglobulin M response at an early stage of disease (19). Interestingly, OspC can protect animals against subsequent infection by the same strain (26) but not by heterologous strains (49). Also, injection with polyclonal and monoclonal antibodies to OspC can cure chronically infected mice and prevent reinfection with the same strain.…”

Section: Discussionmentioning

confidence: 99%

Genetic Diversity of the Outer Surface Protein C Gene of SouthernBorreliaIsolates and Its Possible Epidemiological, Clinical, and Pathogenetic Implications

2002

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The ospC genes of 20 southern Borrelia strains were sequenced. The strains consisted of B. burgdorferi sensu stricto, B. andersonii, B. bissettii, one undescribed genospecies, MI-8, and one probably new Borrelia species, TXW-1. A high degree of similarity exists between B. burgdorferi sensu stricto and B. bissettii and between B. bissettii and B. andersonii. Lateral transfers of the ospC gene probably occurred between B. burgdorferi sensu stricto and B. bissettii and between B. bissettii and B. andersonii. Internal gene recombination appears to occur among them. The highest degree of genetic diversity among them was observed in the two variable domains (V1 and V2), semivariable domain (SV), and the species-specific epitopes (between amino acids 28 and 31). Differences in ospC sequences among southern strains reflect diversity at the strain and genospecies levels. MI-8, which was recognized as an undescribed genospecies in our previous reports, remains distinguishable in our current analysis of ospC genes and is distinct from B. burgdorferi sensu stricto. Interestingly, another undescribed southern isolate, TXW-1, was not amplified under various PCR conditions. Compared to European B. burgdorferi sensu stricto strains, American B. burgdorferi sensu stricto strains show greater genetic heterogeneity. Southern B. burgdorferi sensu stricto, B. andersonii, and B. bissettii isolates were intermixed with each other in the phylogenetic trees. In the derived trees in our work, at least one southeastern strain of B. burgdorferi, MI-2, most closely aligns with a so-called invasive cluster that possesses many proven human-invasive strains. Transmission experiments show that MI-2 and the strains in this group of southern spirochetes are able to infect mice and hamsters and that the typical vector of Lyme disease, Ixodes scapularis, can acquire the spirochetes from infected mammals. Currently, strain MI-2 appears to be the only southern isolate among the 20 we analyzed that clusters with an OspC invasive group and thus might be invasive for humans.

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Immunization with Outer Surface Protein (Osp) A, but Not OspC, Provides Cross-Protection of Mice Challenged with North American Isolates of Borrelia burgdorferi

Cited by 105 publications

References 51 publications

Isolation of Borrelia burgdorferi from Neotoma fuscipes, Peromyscus maniculatus, Peromyscus boylii, and Ixodes pacificus in Oregon.

Isolation of Borrelia burgdorferi from Neotoma fuscipes, Peromyscus maniculatus, Peromyscus boylii, and Ixodes pacificus in Oregon.

Within-host competition betweenBorrelia afzelii ospCstrains in wild hosts as revealed by massively parallel amplicon sequencing

Genetic Diversity of the Outer Surface Protein C Gene of SouthernBorreliaIsolates and Its Possible Epidemiological, Clinical, and Pathogenetic Implications

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