Molecular models accounting for the gene conversion reactions mediating gonococcal pilin antigenic variation

Howell-Adams, Becky; Seifert, H. Steven

doi:10.1046/j.1365-2958.2000.02067.x

Cited by 102 publications

(94 citation statements)

References 48 publications

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“…The apparent necessity for the cis localization of the expression site on the same replicon as the vls silent cassette locus differs from the vlp-vsp antigenic variation systems of relapsing fever spirochetes, in which the silent genes are located on a different plasmid than the expression locus (2,3,43). In addition, it has been shown that pilE recombination can occur in trans in Neisseria gonorrhoeae via a circular intermediate (18), indicating that a novel recombination mechanism may be utilized by the vls system.…”

Section: Discussionmentioning

confidence: 98%

Effects of vlsE Complementation on the Infectivity of Borrelia burgdorferi Lacking the Linear Plasmid lp28-1

2004

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The loss of linear plasmid lp28-1, which contains the vls antigenic variation locus, is associated with reduced infectivity of Borrelia burgdorferi in immunocompetent mice. The recombinant shuttle vector pBBE22, which includes the virulence determinant BBE22 from lp25 and restores infectivity to readily transformable B. burgdorferi lacking lp25 and lp56, was used to determine the effect of trans expression of vlsE on virulence. Spirochetes lacking lp28-1 were complemented with the plasmid pBBE22:vlsE, containing both BBE22 and vlsE. VlsE protein produced by this construct was expressed and surface accessible in in vitro-cultured B. burgdorferi, as determined by surface proteolysis and immunoblot analysis. Clones lacking lp25 but containing lp28-1 and either pBBE22 or pBBE22:vlsE were reisolated consistently from immunocompetent mice 8 weeks after infection. In contrast, a clone lacking both lp25 and lp28-1 and complemented with pBBE22:vlsE was isolated from only a single tissue of one of six C3H/HeN mice 8 weeks postinfection. These results indicate that either an intact vls antigenic variation locus or another determinant on lp28-1 is required to restore complete infectivity. In addition, an isogenic clone that retained lp28-1 was complemented with the vlsE shuttle plasmid and was examined for vlsE sequence variation and infectivity. Sequence variation was not observed for the shuttle plasmid, indicating that the cis arrangement of vlsE and the vls silent cassettes in lp28-1 facilitate vlsE gene conversion. Lack of vlsE sequence variation on the shuttle plasmid thus did not result in clearance of the trans-complemented strain in immunocompetent mice under the conditions tested.Lyme borreliosis, the most prevalent vector-borne disease in the United States, is a chronic infection caused by Borrelia burgdorferi and other members of the genus Borrelia (6). Spirochetes are transmitted to mammalian hosts by Ixodes ticks, leading to the development of an annular rash called erythema migrans at the site of inoculation and progressing to a multisystemic infection with neurological, arthritic, and cardiac manifestations (45). As infection advances and Borrelia disseminate into deeper tissues in the host, a strong immune response is elicited towards the pathogen, including the development of Borrelia-specific antibodies (7,8,11,14,17). Though an active immune response develops early during infection, Borrelia is able to escape clearance and persist for months to years. Elucidation of the mechanisms of immune evasion may lead to a better understanding of the pathobiology of Lyme disease.The vls (Vmp-like sequence) locus of B. burgdorferi B31 is on the linear plasmid lp28-1, a plasmid associated with infectivity in the mouse model (26, 27, 42, 52). The vls locus consists of an expression site (vlsE) and 15 unexpressed (silent) vls cassettes. The silent cassettes have high homology to the central cassette region of vlsE. Within the cassettes, there are six variable regions interspersed between highly conserved regions (52). ...

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Section: Discussionmentioning

confidence: 98%

Effects of vlsE Complementation on the Infectivity of Borrelia burgdorferi Lacking the Linear Plasmid lp28-1

2004

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“…In addition, a link between replication and antigenic variation has been postulated (16). Therefore, we tested whether priA is also associated with these recombination processes in N. gonorrhoeae and whether it plays a role in pilin antigenic variation.…”

Section: Discussionmentioning

confidence: 99%

“…Antigenic variation occurs via a unidirectional homologous recombination event between the pilin coding gene (pilE) and one of multiple unexpressed pilin copies (pilS) found at various sites throughout the chromosome. During pilin antigenic variation, a variable portion of a pilS copy replaces the corresponding portion of pilE, recombining at short regions of identity shared between the silent and expressed genes (16). Pilin antigenic variation is dependent on recA (21), the recF-like pathway (33,57), rdgC (32), and rep (19) as well as the ruvABC and recG branch migration pathways (50).…”

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confidence: 99%

Mutation of the priA Gene of Neisseria gonorrhoeae Affects DNA Transformation and DNA Repair

Kline

Seifert

2005

J Bacteriol

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In Escherichia coli, PriA is central to the restart of chromosomal replication when replication fork progression is disrupted and is also involved in homologous recombination and DNA repair. To investigate the role of PriA in recombination and repair in Neisseria gonorrhoeae, we identified, cloned, and insertionally inactivated the gonococcal priA homologue. The priA mutant showed a growth deficiency and decreased DNA repair capability and was completely for deficient in DNA transformation compared to the isogenic parental strain. The priA mutant was also more sensitive to the oxidative damaging agents H 2 O 2 and cumene hydroperoxide compared to the parental strain. These phenotypes were complemented by supplying a functional copy of priA elsewhere in the chromosome. The N. gonorrhoeae priA mutant showed no alteration in the frequency of pilin antigenic variation. We conclude that PriA participates in DNA repair and DNA transformation processes but not in pilin antigenic variation.

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“…Examples include the pilin genes from Neisseria species (17,21), msp2 from Anaplasma marginale (12,37), porB from Neisseria meningitidis (58), and ompL1 of the Leptospira genus (19). The examples above all involve pathogenic bacteria of vertebrates, and it is believed that recombination and rapid sequence evolution in their surface antigens are selectively advantageous by promoting avoidance of the vertebrate host immune response.…”

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confidence: 99%

Mosaic Nature of theWolbachiaSurface Protein

2005

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Lateral gene transfer and recombination play important roles in the evolution of many parasitic bacteria. Here we investigate intragenic recombination in Wolbachia bacteria, considered among the most abundant intracellular bacteria on earth. We conduct a detailed analysis of the patterns of variation and recombination within the Wolbachia surface protein, utilizing an extensive set of published and new sequences from five main supergroups of Wolbachia. Analysis of nucleotide and amino acid sequence variations confirms four hypervariable regions (HVRs), separated by regions under strong conservation. Comparison of shared polymorphisms reveals a complex mosaic structure of the gene, characterized by a clear intragenic recombining of segments among several distinct strains, whose major recombination effect is shuffling of a relatively conserved set of amino acid motifs within each of the four HVRs. Exchanges occurred both within and between the arthropod supergroups. Analyses based on phylogenetic methods and a specific recombination detection program (MAXCHI) significantly support this complex partitioning of the gene, indicating a chimeric origin of wsp. Although wsp has been widely used to define macro-and microtaxonomy among Wolbachia strains, these results clearly show that it is not suitable for this purpose. The role of wsp in bacterium-host interactions is currently unknown, but results presented here indicate that exchanges of HVR motifs are favored by natural selection. Identifying host proteins that interact with wsp variants should help reveal how these widespread bacterial parasites affect and evolve in response to the cellular environments of their invertebrate hosts.

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Molecular models accounting for the gene conversion reactions mediating gonococcal pilin antigenic variation

Cited by 102 publications

References 48 publications

Effects of vlsE Complementation on the Infectivity of Borrelia burgdorferi Lacking the Linear Plasmid lp28-1

Effects of vlsE Complementation on the Infectivity of Borrelia burgdorferi Lacking the Linear Plasmid lp28-1

Mutation of the priA Gene of Neisseria gonorrhoeae Affects DNA Transformation and DNA Repair

Mosaic Nature of theWolbachiaSurface Protein

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