Effect of
            <i>Borrelia burgdorferi</i>
            OspC at the Site of Inoculation in Mouse Skin

Antonara, Styliani; Ristow, Laura C.; McCarthy, James J.; Coburn, Jenifer

doi:10.1128/iai.00464-10

Cited by 27 publications

(23 citation statements)

References 65 publications

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“…Although previous reports showed that neutrophils effectively control spirochete burden in tissues from mice infected with wildtype spirochetes (74,75), our data indicated that neutrophils were not the major factor in clearing the ospC mutant at the skin site of inoculation in mice. This finding is consistent with a previous study showing no differences in neutrophil infiltration in skin biopsy specimens from mice challenged with wild-type or ospC mutant spirochetes (59). In contrast, we found that depletion of mononuclear phagocytes at the skin site of inoculation in SCID and C3H/HeN mice allowed the ospC mutant to establish infection and dissemination, suggesting that these innate cells were indispensable in clearing the ospC mutant.…”

Section: Discussionsupporting

confidence: 93%

“…Our results showed that the ospC mutant also was not able to establish infection in NODSCIDg mice when inoculated at the standard dose (10 3 spirochetes per mouse). The same inoculum of ospC mutant spirochetes cannot cause infection in C3H/HeN and SCID mice, which is what we observed in our infectivity experiments using these mouse strains (8,17,21,59). Our findings suggest that the lytic complement and NK cells were dispensable in the clearance of the ospC mutant.…”

Section: Discussionsupporting

confidence: 83%

“…injected with either wild-type B31-A3 or the ospC mutant. We used an inoculum of 10 3 spirochetes per mouse, as previously reported (8,17,21,59). NODSCIDg mice were also inoculated intravenously to assess whether the injection site plays a role in the infectivity of the ospC mutant.…”

Section: Resultsmentioning

confidence: 99%

“…Our results also support the previous observation that depletion of NK cells did not have a major effect on B. burgdorferi burden and dissemination in arthritis-resistant and -susceptible mouse strains (72). In this study, we focused on professional phagocytes as one of the primary target cells for our depletion studies, as phagocytes were reported to infiltrate the skin site of inoculation or to be elevated systemically in mice infected with B. burgdorferi (59,73). Our result showed that the ospC mutant was cleared within the first 48 h postchallenge in neutropenic SCID and C3H/HeN mice.…”

Section: Discussionmentioning

confidence: 99%

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Outer Surface Protein OspC Is an Antiphagocytic Factor That Protects Borrelia burgdorferi from Phagocytosis by Macrophages

et al. 2015

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cOuter surface protein C (OspC) is one of the major lipoproteins expressed on the surface of Borrelia burgdorferi during tick feeding and the early phase of mammalian infection. OspC is required for B. burgdorferi to establish infection in both immunocompetent and SCID mice and has been proposed to facilitate evasion of innate immune defenses. However, the exact biological function of OspC remains elusive. In this study, we showed that the ospC-deficient spirochete could not establish infection in NOD-scid IL2r␥ null mice that lack B cells, T cells, NK cells, and lytic complement. The ospC mutant also could not establish infection in anti-Ly6G-treated SCID and C3H/HeN mice (depletion of neutrophils). However, depletion of mononuclear phagocytes at the skin site of inoculation in SCID and C3H/HeN mice allowed the ospC mutant to establish infection in vivo. In phagocyte-depleted mice, the ospC mutant was able to colonize the joints and triggered neutrophilia during dissemination. Furthermore, we found that phagocytosis of green fluorescent protein (GFP)-expressing ospC mutant spirochetes by murine peritoneal macrophages and human THP-1 macrophage-like cells, but not in PMN-HL60, was significantly higher than parental wild-type B. burgdorferi strains, suggesting that OspC has an antiphagocytic property. In addition, overproduction of OspC in spirochetes also decreased the uptake of spirochetes by murine peritoneal macrophages. Together, our findings provide evidence that mononuclear phagocytes play a key role in clearance of the ospC mutant and that OspC promotes spirochetes' evasion of macrophages during early Lyme borreliosis. L yme disease, the most prevalent vector-borne illness in the United States (1), is a multisystem inflammatory disorder caused by infection with the spirochete Borrelia burgdorferi (2, 3). This spirochete is maintained in nature through a complex enzootic cycle involving Ixodes ticks and various small-mammal hosts. Humans, as accidental hosts, become infected after B. burgdorferiinfected ticks feed on them (4). Spirochetes replicate in the skin, spread locally, and induce an inflammatory response with a symptom known as erythema migrans, observed in most patients (2, 4). During disseminated infection, B. burgdorferi colonizes multiple tissues, leading to different clinical manifestations, including arthritis, myocarditis, and neurological and/or cutaneous abnormalities (2, 4). This acute, disseminated stage of human Lyme disease is largely recapitulated using inbred mouse strains which are susceptible to B. burgdorferi infection and develop carditis and subacute arthritis (5). Thus, the murine model provides a powerful tool to elucidate the role of spirochete virulence factors and host immunological responses during Lyme disease pathogenesis (4).The B. burgdorferi genome encodes a large number of surface lipoproteins, many of which are expressed during mammalian infection (4, 6, 7). One of these lipoproteins is the major outer surface protein C (OspC), whose production is induced within inf...

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Outer Surface Protein OspC Is an Antiphagocytic Factor That Protects Borrelia burgdorferi from Phagocytosis by Macrophages

et al. 2015

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“…While specific molecular functions of OspC are not yet clear, it is known that ospC is required for host infection and is among the most differentially expressed genes during host invasion (Brooks et al 2003;Grimm et al 2004;Liang et al 2004;Tilly et al 2006;Antonara et al 2010). Considering that ospC is a serotype determinant of B. burgdorferi s.l., negative FDS operating at ospC is highly plausible.…”

Section: Maintenance Of Genome Clusters By Frequency-dependent Selectionmentioning

confidence: 99%

Pervasive Recombination and Sympatric Genome Diversification Driven by Frequency-Dependent Selection in Borrelia burgdorferi, the Lyme Disease Bacterium

Vargas²,

et al. 2011

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How genomic diversity within bacterial populations originates and is maintained in the presence of frequent recombination is a central problem in understanding bacterial evolution. Natural populations of Borrelia burgdorferi, the bacterial agent of Lyme disease, consist of diverse genomic groups co-infecting single individual vertebrate hosts and tick vectors. To understand mechanisms of sympatric genome differentiation in B. burgdorferi, we sequenced and compared 23 genomes representing major genomic groups in North America and Europe. Linkage analysis of .13,500 single-nucleotide polymorphisms revealed pervasive horizontal DNA exchanges. Although three times more frequent than point mutation, recombination is localized and weakly affects genome-wide linkage disequilibrium. We show by computer simulations that, while enhancing population fitness, recombination constrains neutral and adaptive divergence among sympatric genomes through periodic selective sweeps. In contrast, simulations of frequency-dependent selection with recombination produced the observed pattern of a large number of sympatric genomic groups associated with major sequence variations at the selected locus. We conclude that negative frequency-dependent selection targeting a small number of surface-antigen loci (ospC in particular) sufficiently explains the maintenance of sympatric genome diversity in B. burgdorferi without adaptive divergence. We suggest that pervasive recombination makes it less likely for local B. burgdorferi genomic groups to achieve host specialization. B. burgdorferi genomic groups in the northeastern United States are thus best viewed as constituting a single bacterial species, whose generalist nature is a key to its rapid spread and human virulence. G ENETIC discontinuity, the basis of biodiversity, is ubiquitous in prokaryotes as well as in eukaryotes. Most bacterial populations display a highly clonal genetic structure, in which the observable number of multilocus genotypes is far fewer than the number expected under the assumption of free recombination (Maynard Smith et al. 1993). Bacterial clonality was originally thought of as a result of a lack or rarity of recombination among asexually reproducing and independently evolving clones (Ochman and Selander 1984). Since then, molecular surveys of natural bacterial populations using protein electrophoresis, multilocus sequencing typing (MLST), and whole-genome PRJNA3, PRJNA28633, PRJNA19839, PRJNA29359, PRJNA28629, PRJNA29357, PRJNA21003, PRJNA19835, PRJNA28627, PRJNA21001, PRJNA29361, PRJNA28621, PRJNA19837, PRJNA20999, PRJNA28631, PRJNA29363, PRJNA17057, PRJNA19841, PRJNA12554, PRJNA28625, PRJNA29573, PRJNA19843, and PRJNA28635. 1 Present address: Odum School of Ecology, University of Georgia, Athens, GA 30602. sequencing revealed that horizontal genetic exchange is in fact often more frequent than point mutations in bacteria, including species known as strongly clonal (Maynard Smith et al. 1993;Feil and Spratt 2001;Didelot and Maiden 2010;Retc...

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