<i>Borrelia burgdorferi</i> adhesins identified using <i>in vivo</i> phage display

Antonara, Styliani; Chafel, R.; LaFrance, Michelle E.; Coburn, Jenifer

doi:10.1111/j.1365-2958.2007.05924.x

Cited by 89 publications

(119 citation statements)

References 65 publications

(109 reference statements)

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“…Surprisingly, the role of OspC in mammalian infection can be partially replaced by the overexpression of other B. burgdorferi lipoproteins, although the mechanism of this phenomenon has not been investigated (62). Curiously, though, this work revealed a critical role for OspC in the colonization of some of the tissues examined, particularly in the heart, which is consistent with previously published results from two other laboratories (2,28). A specific function for OspC in infection is supported by the recent demonstration that a site-directed change of one residue in a putative ligandbinding pocket rendered the bacteria noninfectious in the mouse model of infection (17).…”

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confidence: 81%

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Effect of Borrelia burgdorferi OspC at the Site of Inoculation in Mouse Skin

et al. 2010

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The Borrelia burgdorferi surface lipoprotein OspC is a critical virulence factor, but its precise role in the establishment of B. burgdorferi infection remains unclear. To determine whether OspC affects the host response at the site of inoculation of the bacterium, the recruitment of macrophages and neutrophils and the production of cytokines were examined at the site of infection by wild-type, ospC mutant, and complemented mutant B. burgdorferi strains. Of the 21 cytokines tested, monocyte chemoattractant protein 1 (MCP-1), keratinocyte-derived chemokine (KC, CXCL1), and vascular endothelial growth factor (VEGF) were found at increased levels at the site of inoculation of B. burgdorferi, and the levels varied with the production of OspC at one or more time points over the 1-week course of infection. The kinetics of expression and the dependence on OspC production by B. burgdorferi varied among the cytokines. The production of KC and MCP-1, and the appearance of monocytic infiltrates, correlated with the presence of the bacteria rather than with OspC specifically. In contrast, VEGF production was not correlated simply to the presence of the bacteria and is influenced by the presence of OspC. In in vitro assays, OspC and B. burgdorferi expressing OspC stimulated the growth of endothelial cells more than did the controls. These data suggest the possibility of a novel role for OspC in the life of B. burgdorferi at the interface of its mammalian and tick hosts.

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confidence: 81%

“…Purified maltosebinding protein (MBP)-␤-galactosidase (␤gal) and MBP-OspC were described previously (2). Purified proteins were tested at 1 and 10 g/ml.…”

Section: Methodsmentioning

confidence: 99%

Effect of Borrelia burgdorferi OspC at the Site of Inoculation in Mouse Skin

et al. 2010

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“…Research on the borrelial Erp outer surface proteins has revealed multiple properties associated with mammalian infection (2,3,11,12,34,37,40,45,59). Given what is known of their functions, it is not surprising that B. burgdorferi Erp proteins are produced during mammalian infection but repressed during colonization of tick vectors (10,31,48,49).…”

Section: Discussionmentioning

confidence: 99%

“…Erp proteins are located in the bacterial outer membrane and are exposed to the external environment (25,32,41). Known functions of Erp proteins include binding of host plasmin(ogen), laminin, and the complement regulators factor H and factor H-related proteins 1, 2, and 5 (2,3,11,12,34,37,40,45,59). These functions indicate roles for Erp proteins in host adherence, dissemination, and resistance to the alternative pathway of complement-mediated killing.…”

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confidence: 99%

BpaB and EbfC DNA-Binding Proteins Regulate Production of the Lyme Disease Spirochete's Infection-Associated Erp Surface Proteins

et al. 2012

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Successful infection of a host requires that the invading pathogen control its production of virulence determinants. The infectious agent must sense its environment and respond by increasing production of appropriate factors and repressing production of unnecessary ones. These features are especially critical for vector-borne pathogens, which must not only efficiently infect two extremely different host types but also be transmitted back and forth between hosts. Deciphering the regulatory pathways used by pathogens to control production of infection-associated proteins provides significant insight into the infectious nature of those organisms. Moreover, regulatory factors are attractive candidates for development of novel preventative and curative therapies.The spirochetal bacterium Borrelia burgdorferi, the agent of Lyme disease, is an excellent model organism for the study of gene regulation by a vector-borne pathogen. B. burgdorferi is genetically tractable, and its natural mammal-tick infectious cycle can be replicated in the laboratory. In addition, infection by B. burgdorferi is a significant cause of human morbidity, being the most commonly reported vector-borne disease in the United States and many other parts of the world (51, 55, 56).B. burgdorferi Erp lipoproteins are produced throughout mammalian infection but are largely repressed during colonization of vector ticks (10,31,48,49). Erp synthesis is greatly enhanced when B. burgdorferi is transmitted from a feeding tick into a warm-blooded host. Regulation of Erp protein production is controlled at the level of transcription (6). Erp proteins are located in the bacterial outer membrane and are exposed to the external environment (25,32,41). Known functions of Erp proteins include binding of host plasmin(ogen), laminin, and the complement regulators factor H and factor H-related proteins 1, 2, and 5 (2,3,11,12,34,37,40,45,59). These functions indicate roles for Erp proteins in host adherence, dissemination, and resistance to the alternative pathway of complement-mediated killing. Borrelial erp genes are located in mono-or bicistronic operons on extrachromosomal cp32 prophages, most of which replicate autonomously as circular episomes (24,60,63,64,72). Individual Lyme spirochetes naturally contain numerous different cp32 elements, each with a unique erp locus, and therefore produce multiple, distinct Erp surface proteins. A bacterium simultaneously expresses its entire repertoire of Erp proteins (26).A highly conserved DNA region immediately 5= of all erp promoters, the erp operator, is required for regulation of erp transcription (see Fig. 1) (6,10,64). Two erp operator-binding proteins have been identified, and their binding sites have been characterized: BpaB (borrelial plasmid ParB analogue) and EbfC (erp-binding factor, chromosomal) (4, 13, 52). BpaB binds with high affinity to a 5-bp sequence within the erp operator (13; C. A. Adams, unpublished). Binding of one BpaB protein to that sequence then facilitates binding of additional BpaB molecules al...

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“…Additionally, bba66 is expressed during persistent mouse infection, suggestive of a maintenance function for B. burgdorferi in a reservoir host or as a needed component to colonize host tissues (14,17). Studies by Anguita et al suggested that bba66 may play a role in Lyme arthritis and carditis as assessed in the C3H/HeN mouse model (21), and Antonara et al found evidence for BBA66 adhesion to murine heart tissue by phage display assay (22). Like other genes in this complex, notably bba64, bba66 is controlled by the Rrp2-RpoN-RpoS global regulation pathway, which regulates a subset of genes both in the tick transition portion of the enzootic cycle and during mammalian infection (7,13,16,(23)(24)(25)(26).…”

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confidence: 99%

Borrelia burgdorferi bba66 Gene Inactivation Results in Attenuated Mouse Infection by Tick Transmission

et al. 2013

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bThe impact of the Borrelia burgdorferi surface-localized immunogenic lipoprotein BBA66 on vector and host infection was evaluated by inactivating the encoding gene, bba66, and characterizing the mutant phenotype throughout the natural mouse-tickmouse cycle. The BBA66-deficient mutant isolate, Bb ⌬A66 , remained infectious in mice by needle inoculation of cultured organisms, but differences in spirochete burden and pathology in the tibiotarsal joint were observed relative to the parental wild-type (WT) strain. Ixodes scapularis larvae successfully acquired Bb ⌬A66 following feeding on infected mice, and the organisms persisted in these ticks through the molt to nymphs. A series of tick transmission experiments (n ‫؍‬ 7) demonstrated that the ability of Bb ⌬A66 -infected nymphs to infect laboratory mice was significantly impaired compared to that of mice fed upon by WT-infected ticks. trans-complementation of Bb ⌬A66 with an intact copy of bba66 restored the WT infectious phenotype in mice via tick transmission. These results suggest a role for BBA66 in facilitating B. burgdorferi dissemination and transmission from the tick vector to the mammalian host as part of the disease process for Lyme borreliosis.

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Borrelia burgdorferi adhesins identified using in vivo phage display

Cited by 89 publications

References 65 publications

Effect of Borrelia burgdorferi OspC at the Site of Inoculation in Mouse Skin

Effect of Borrelia burgdorferi OspC at the Site of Inoculation in Mouse Skin

BpaB and EbfC DNA-Binding Proteins Regulate Production of the Lyme Disease Spirochete's Infection-Associated Erp Surface Proteins

Borrelia burgdorferi bba66 Gene Inactivation Results in Attenuated Mouse Infection by Tick Transmission

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