Fast, adaptive evolution at a bacterial host-resistance locus: The PFam54 gene array in Borrelia burgdorferi

Wywiał, Ewa; Haven, James; Casjens, Sherwood; Hernández, Yözen; Singh, Shaneen; Mongodin, Emmanuel F.; Fraser, Claire M.; Luft, Benjamin J.; Schutzer, Steven E.; Qiu, Wei

doi:10.1016/j.gene.2009.05.017

Cited by 48 publications

(59 citation statements)

References 59 publications

(89 reference statements)

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“…PCR with these primers resulted in the generation of amplicons ϳ1 kb in size, which were inserted into pCR-XL-TOPO vector (Invitrogen) and then sequenced. Nucleotide sequence analysis showed that dbpA cloned from strains B31, 297, PBr, and VS461 were identical to previously published sequences (44,60). DbpA from strain N40 D10/E9 was found to be 95% identical to DbpA from an independent clone of N40 (44) and is, for clarity, referred to as DbpA N40-D10/E9 in the present study.…”

Section: Methodssupporting

confidence: 84%

Allelic Variation of the Lyme Disease Spirochete Adhesin DbpA Influences Spirochetal Binding to Decorin, Dermatan Sulfate, and Mammalian Cells

et al. 2011

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After transmission by an infected tick, the Lyme disease spirochete, Borrelia burgdorferi sensu lato, colonizes the mammalian skin and may disseminate systemically. The three major species of Lyme disease spirochete-B. burgdorferi sensu stricto, B. garinii, and B. afzelii-are associated with different chronic disease manifestations. Colonization is likely promoted by the ability to bind to target tissues, and Lyme disease spirochetes utilize multiple adhesive molecules to interact with diverse mammalian components. The allelic variable surface lipoprotein decorin binding protein A (DbpA) promotes bacterial binding to the proteoglycan decorin and to the glycosaminoglycan (GAG) dermatan sulfate. To assess allelic variation of DbpA in GAG-, decorin-, and cell-binding activities, we expressed dbpA alleles derived from diverse Lyme disease spirochetes in B. burgdorferi strain B314, a noninfectious and nonadherent strain that lacks dbpA. Each DbpA allele conferred upon B. burgdorferi strain B314 the ability to bind to cultured kidney epithelial (but not glial or endothelial) cells, as well as to purified decorin and dermatan sulfate. Nevertheless, allelic variation of DbpA was associated with dramatic differences in substrate binding activity. In most cases, decorin and dermatan sulfate binding correlated well, but DbpA of B. afzelii strain VS461 promoted differential binding to decorin and dermatan sulfate, indicating that the two activities are separable. DbpA from a clone of B. burgdorferi strain N40 that can cause disseminated infection in mice displayed relatively low adhesive activity, indicating that robust DbpA-mediated adhesive activity is not required for spread in the mammalian host.

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Section: Methodssupporting

confidence: 84%

Allelic Variation of the Lyme Disease Spirochete Adhesin DbpA Influences Spirochetal Binding to Decorin, Dermatan Sulfate, and Mammalian Cells

et al. 2011

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“…This is similar to the finding that the locations of important virulence factor-encoding genes, such as dbpA-dbpB, ospA-ospB, and ospC, are conserved in particular genome segments, even though sizes may be somewhat different due to genetic rearrangements, especially on the outer edges of the linear plasmids. Gene duplication followed by rearrangement and mutations appear to have resulted in the evolution and antigenic variation of a number of B. burgdorferi virulence factors and other proteins (4,28,43,62,82,97,109,110). Often, duplicated genes that encode functionally redundant proteins that exhibit overlapping roles are present in the same operon, with each protein demonstrating altered specificities for host cell factors.…”

Section: Discussionmentioning

confidence: 99%

Detection of Established Virulence Genes and Plasmids To Differentiate Borrelia burgdorferi Strains

2012

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ABSTRACTBorrelia burgdorferisensu stricto is the major causative agent of Lyme disease in the United States, whileB. gariniiandB. afzeliiare more prevalent in Europe. The highly complex genome ofB. burgdorferiis comprised of a linear chromosome and a large number of variably sized linear and circular plasmids. Many plasmids of this spirochete are unstable during its culturein vitro. Given that many of theB. burgdorferivirulence factors identified to date are plasmid encoded, spirochetal plasmid content determination is essential for genetic analysis of Lyme pathogenesis. Although PCR-based assays facilitate plasmid profiling of sequencedB. burgdorferistrains, a rapid genetic content determination strategy for nonsequenced strains has not yet been described. In this study, we combined pulsed-field gel electrophoresis (PFGE) and Southern hybridization for detection of genes encoding known virulence factors,ribosomal RNA genespacer restriction fragment length polymorphismtypes (RSTs),ospCgroup determination, and sequencing of the variabledbpAandospCgenes. We show that two strains isolated from the same tick and both originally named N40 are in fact very distinct. Furthermore, we failed to detectbbk32, which encodes a fibronectin-binding adhesin, in one “N40” strain. Thus, two distinct strains that show different plasmid profiles, as determined by PFGE and PCR, were isolated from the same tick and vary in theirospCanddbpAsequences. However, both belong to group RST3B.

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“…All putative ORFs were searched against the National Center for Biotechnology Information (NCBI) nonredundant protein database using BLASTp (see Tables S2 and S3 in the supplemental material) (41). The BLAST search criteria for designating an ORF as homologous to a deduced protein of an LD Borrelia species or another organism were the following: E values of Ͻ10 Ϫ5 , pairwise amino acid identities of Ͼ20%, and Ͼ50% coverage of the smaller protein (42,43). ORFs were analyzed using a collection of protein families represented by hidden Markov models (HMM) constructed from family member seed alignments (protein family A) or from unannotated and automatically generated nonredundant clusters (protein family B) with Pfam version 24.0 using HMMER3 (http://pfam.sanger.ac.uk/) (44).…”

Section: Methodsmentioning

confidence: 99%

Large Linear Plasmids of Borrelia Species That Cause Relapsing Fever

et al. 2013

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c Borrelia species of relapsing fever (RF) and Lyme disease (LD) lineages have linear chromosomes and both linear and circular plasmids. Unique to RF species, and little characterized to date, are large linear plasmids of ϳ160 kb, or ϳ10% of the genome. By a combination of Sanger and next-generation methods, we determined the sequences of large linear plasmids of two New World species: Borrelia hermsii, to completion of its 174-kb length, and B. turicatae, partially to 114 kb of its 150 kb. These sequences were then compared to corresponding sequences of the Old World species B. duttonii and B. recurrentis and to plasmid sequences of LD Borrelia species. The large plasmids were largely colinear, except for their left ends, about 27 kb of which was inverted in New World species. Approximately 60% of the B. hermsii lp174 plasmid sequence was repetitive for 6 types of sequence, and half of its open reading frames encoded hypothetical proteins not discernibly similar to proteins in the database. The central ϳ25 kb of all 4 linear plasmids was syntenic for orthologous genes for plasmid maintenance or partitioning in Borrelia species. Of all the sequenced linear and circular plasmids in Borrelia species, the large plasmid's putative partition/replication genes were most similar to those of the 54-kb linear plasmids of LD species. Further evidence for shared ancestry was the observation that two of the hypothetical proteins were predicted to be structurally similar to the LD species' CspA proteins, which are encoded on the 54-kb plasmids.

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Fast, adaptive evolution at a bacterial host-resistance locus: The PFam54 gene array in Borrelia burgdorferi

Cited by 48 publications

References 59 publications

Allelic Variation of the Lyme Disease Spirochete Adhesin DbpA Influences Spirochetal Binding to Decorin, Dermatan Sulfate, and Mammalian Cells

Allelic Variation of the Lyme Disease Spirochete Adhesin DbpA Influences Spirochetal Binding to Decorin, Dermatan Sulfate, and Mammalian Cells

Detection of Established Virulence Genes and Plasmids To Differentiate Borrelia burgdorferi Strains

Large Linear Plasmids of Borrelia Species That Cause Relapsing Fever

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