Outer-surface protein C of the Lyme disease spirochete: A protein induced in ticks for infection of mammals

Grimm, Dorothee; Tilly, Kit; Byram, Rebecca; Stewart, Philip E.; Krum, Jonathan G.; Bueschel, Dawn M.; Schwan, Tom G.; Policastro, Paul F.; Elias, Abdallah F.; Rosa, Patricia A.

doi:10.1073/pnas.0306845101

Cited by 377 publications

(460 citation statements)

References 43 publications

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“…Similarly, Mn, possibly via the Mn-dependent Fur homolog BosR (23,33,37,38) Our study has demonstrated that the Lyme disease spirochete requires BmtA's Mn-associated transport function(s) to maintain its infectious cycle in nature. To date, only relatively few virulence factors, including OspC, DbpB/A, OspA/B, PncA, and BptA, have been identified in Bb, and the functions of most of these proteins remain obscure (4,5,(7)(8)(9)(10). In this regard, our identification of BmtA as a novel virulence factor in Bb provides further insights into molecular mechanisms that contribute to Bb's survival in nature and may lead to new strategies to interrupt the spirochete life cycle.…”

Section: Discussionmentioning

confidence: 95%

“…In recent years, extensive efforts have been directed toward elucidating the mechanisms by which Bb cycles, adapts, and sustains itself in these diverse niches. It is now well established that outer surface (lipo)protein C (OspC), OspA/B, decorin-binding protein B/A (DbpB/A), PncA, and BptA are required by Bb for efficient infection of ticks or mammalian hosts (4)(5)(6)(7)(8)(9)(10). It is also generally accepted that the recently discovered Rrp2-RpoN ( 54 )-RpoS ( S ) regulatory pathway plays prominently in Bb's virulence expression (11)(12)(13)(14).…”

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confidence: 99%

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A manganese transporter, BB0219 (BmtA), is required for virulence by the Lyme disease spirochete, Borrelia burgdorferi

Ouyang

Oman

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

131

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Borrelia burgdorferi (Bb), the causative agent of Lyme disease, is transmitted to mammalian hosts through an arthropod (tick) vector. To establish infection, Bb must acquire essential nutrients, including transition metals, from its mammalian and tick hosts. Thus far, no metal transporter has been identified in Bb. Here, we report the identification of the first metal transporter, BmtA (BB0219), in Bb. BmtA-deficient mutants of virulent Bb were readily generated, and the mutants grew slightly slower than wild-type Bb in vitro. However, BmtA mutants were sensitive to the chelating actions of EDTA, suggesting a role for BmtA in metal utilization. Intracellular accumulation of manganese (Mn) was substantially diminished in the bmtA mutant, indicating that BmtA was operative in Mn uptake. Given that BmtA lacks homology to any known Mn transporter, we postulate that BmtA is part of a novel mechanism for Mn acquisition by a bacterial pathogen. BmtA also was essential to the infectious life cycle of Bb in ticks and mammals, thereby qualifying BmtA as a new borrelial virulence factor. In addition, the bmtA mutant was sensitive to treatment with t-butyl hydroperoxide, implying that BmtA, and thus Mn, is important to Bb for detoxifying reactive oxygen species, including those potentially liberated by immune effector cells during the innate immune response. Our discovery of the first molecule involved in metal transport in Bb provides a foundation for further elucidating metal homeostasis in this important human pathogen, which may lead to new strategies for thwarting Lyme disease. metal transport ͉ pathogenesis

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

A manganese transporter, BB0219 (BmtA), is required for virulence by the Lyme disease spirochete, Borrelia burgdorferi

Ouyang

Oman

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

131

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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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“…Some are involved in early infection, such as OspC [112][113][114][115][116], which are presumably required for host colonization or resistance to innate immunity. Others are involved in resistance to acquired immunity, such as VlsE [13,109,117,118].…”

Section: B Burgdorferi Products Required For Mammalian Infectionmentioning

confidence: 99%

“…The OspC product has been shown to be required for an early stage of mammalian infection [113][114][115][116] and conflicting data have been presented regarding its importance in tick transmission [113,114,119,120]. OspC production begins in feeding ticks (or immediately after needle inoculation, Fig.…”

Section: B Burgdorferi Products Required For Mammalian Infectionmentioning

confidence: 99%

Biology of Infection with Borrelia burgdorferi

Tilly

Rosa

Stewart

2008

Infectious Disease Clinics of North America

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177

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The spirochete Borrelia burgdorferi is a tick-borne obligate parasite whose normal reservoir is a variety of small mammals [1]. Whereas infection of these natural hosts does not lead to disease, infection of humans can result in Lyme disease, as a consequence of the human immunopathological response to B. burgdorferi [2,3]. Consistent with the pathogenesis of Lyme disease, bacterial products that allow B. burgdorferi to replicate and survive, rather than true "virulence factors," appear to be primarily what is required for the bacterium to cause disease in a susceptible host. In support of this idea, the genome sequence of B31, the type strain of B. burgdorferi sensu stricto [4,5], revealed that the bacterium lacks factors common to many bacterial pathogens, such as lipopolysaccharide, toxins, and specialized secretion systems. In this chapter, we will describe the basic biology of B. burgdorferi, and some of the bacterial components required to infect and survive in the mammalian and tick hosts.

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Outer-surface protein C of the Lyme disease spirochete: A protein induced in ticks for infection of mammals

Cited by 377 publications

References 43 publications

A manganese transporter, BB0219 (BmtA), is required for virulence by the Lyme disease spirochete, Borrelia burgdorferi

A manganese transporter, BB0219 (BmtA), is required for virulence by the Lyme disease spirochete, Borrelia burgdorferi

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

Biology of Infection with Borrelia burgdorferi

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