Complementation of a Borrelia afzelii OspC mutant highlights the crucial role of OspC for dissemination of Borrelia afzelii in Ixodes ricinus

Fingerle, Volker; Goettner, Gereon; Gern, Lise; Wilske, Bettina; Schulte-Spechtel, Ulrike

doi:10.1016/j.ijmm.2006.11.003

Cited by 67 publications

(48 citation statements)

References 44 publications

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“…The pathogen abundantly expresses OspA/B in the unfed tick [3][4][5][6], consistent with an important role of these lipoproteins in spirochetal persistence in the vector [7,8]. A fresh blood meal down-regulates OspA/B and up-regulates OspC and others, a process that prepares B. burgdorferi for infection of mammals, regardless of whether OspC is required for salivary gland invasion [9][10][11][12]. Repression of OspA/B expression in mammals is critical for the maintenance of the enzootic cycle because their expression would ultimately induce a strong humoral response and, as a result, may effectively block acquisition of B. burgdorferi by the vector [13][14][15], regardless of whether OspA/B can be targeted by borreliacidal antibodies in mammalian tissues [16].…”

Section: Introductionmentioning

confidence: 81%

Verification and dissection of the ospC operator by using flaB promoter as a reporter in Borrelia burgdorferi

McShan

Liang

2008

Microbial Pathogenesis

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The Lyme disease spirochete Borrelia burgdorferi must repress expression of outer surface protein C (OspC) to effectively evade specific humoral immunity and to establish persistent infection. This ability largely relies upon a regulatory element, the only operator that has been reported in spirochetal bacteria. Immediately upstream of the ospC promoter, two sets of inverted repeats (IRs) constitute small and large palindromes, in which the right IR of the large palindrome contains the left IR of the small one, and may collectively function as the ospC operator. In the study, the large palindrome with or without the small IR was fused with a flaB promoter, which was used to drive expression of a promoterless ospC copy as a reporter gene, and introduced into OspC-deficient B. burgdorferi. The presence of the large palindrome alone significantly reduced ospC expression driven by the fused flaB promoter in the joint tissue of severe combined immunodeficiency (SCID) mice, and rescued spirochetes from elimination by passively transferred OspC antibody in infected SCID mice and specific immune responses elicited in immunocompetent mice, confirming a function of the IRs as an operator. Inclusion of the small IR further enhanced the ability of the large palindrome to reduce the activity of the fused flaB promoter, indicating that the small IR is a part of the operator. Taken together, the study led to successful verification and dissection of the ospC operator.

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Section: Introductionmentioning

confidence: 81%

Verification and dissection of the ospC operator by using flaB promoter as a reporter in Borrelia burgdorferi

McShan

Liang

2008

Microbial Pathogenesis

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“…Mutant Borrelias with genetic changes at its different genes has been previously described by MALAWISTA et al 23 , SADZIENE et al 31,32,33 , FINGERLE et al 14 , MOTALEB et al 28 , CHARON et al 9 . The existence of mutant spirochete expressed at atypical cystic morphologies, possibly without periplasmic flagella and decreased expression of outer surface proteins (Osp), justify all the particularities found in BYS.…”

Section: Introductionmentioning

confidence: 87%

Profile of patients with Baggio-Yoshinari Syndrome admitted at "Instituto de Infectologia Emilio Ribas"

Gouveia

Alves

Mantovani

et al. 2010

Rev. Inst. Med. trop. S. Paulo

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SUMMARYThe aim of this study was to evaluate the epidemiological, clinical and laboratorial profile of patients with Baggio-Yoshinari Syndrome (BYS), who underwent internment at the Instituto de Infectologia Emilio Ribas in São Paulo, Brazil, during the period from July 1990 to July 2006. BYS is a new Brazilian tick-borne disease caused by Borrelia burgdorferi sensu lato microorganisms that resembles features of Lyme disease (LD), except for its epidemiological, clinical and laboratorial particularities. From 60 patients' records with positive serology to B. burgdorferi done by ELISA and Western-blotting methods, 19 cases were diagnosed as having BYS, according to criteria adopted at LIM-17 HCFMUSP, the Brazilian Reference Laboratory for the research of BYS. The other 41 remaining patients displayed miscellaneous infections or auto-immune processes. The beginning of symptoms in BYS group varied from one day to six years, from the onset of the disease. Four of 19 patients were included in acute disease stage, and 15 in latent. General unspecific symptoms were identified in almost all cases, with high frequencies of fever (78.9%) and lymphadenomegaly (36.8%). Six patients had skin lesions (31.5%); six arthralgia or arthritis (31.5%) and eight neurological symptoms (42%). Interestingly, two patients showed antibodies directed to B. burgdorferi exclusively in cerebrospinal fluid. Since BYS is a new emergent Brazilian zoonosis and its diagnosis is sometimes complex, all the new knowledge about BYS must be scattered to Brazilian Medical specialists, aiming to teach them how to diagnose this amazing tick-borne disease and to avoid its progression to chronic irreversible sequels.

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“…As one of the strategies to evade host humoral responses, spirochetes downregulate OspC production in response to anti-OspC antibodies within 2 to 3 weeks after infection in mice (12,13). OspC has been shown to be required for B. burgdorferi to establish infection in mammals (8,14), as well as for spirochetal transmission from ticks to mammals (15,16). Infectivity studies demonstrate that the ospC mutant cannot establish infection in immunocompetent and SCID mice (lacking B and T cells) when inoculated at a dose of 10 3 to 10 5 spirochetes per mouse (8,(16)(17)(18)(19)(20).…”

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confidence: 99%

“…OspC has been shown to be required for B. burgdorferi to establish infection in mammals (8,14), as well as for spirochetal transmission from ticks to mammals (15,16). Infectivity studies demonstrate that the ospC mutant cannot establish infection in immunocompetent and SCID mice (lacking B and T cells) when inoculated at a dose of 10 3 to 10 5 spirochetes per mouse (8,(16)(17)(18)(19)(20). The ospC mutant is cleared within the first 48 h of infection in the murine host (21), suggesting a protective role of OspC against innate defenses.…”

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confidence: 99%

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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Complementation of a Borrelia afzelii OspC mutant highlights the crucial role of OspC for dissemination of Borrelia afzelii in Ixodes ricinus

Cited by 67 publications

References 44 publications

Verification and dissection of the ospC operator by using flaB promoter as a reporter in Borrelia burgdorferi

Verification and dissection of the ospC operator by using flaB promoter as a reporter in Borrelia burgdorferi

Profile of patients with Baggio-Yoshinari Syndrome admitted at "Instituto de Infectologia Emilio Ribas"

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

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