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Chapter 41 : Antigenic Variation by Relapsing Fever Borrelia Species and Other Bacterial Pathogens

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Abstract:

This chapter provides examples of antigenic variation that meet three criteria. (i) There is evidence that variation is mainly for avoidance of the host’s immune response or niche selection, i.e., adaptation to different microenvironments in the host, or both. (ii) The variation is multiphasic rather than biphasic. In other words, the repertoire of variable antigens is at least three. There is not a flip-flop between two antigen states, as occurs with some DNA inversion systems. (iii) The mechanism for antigenic variation is most consistent with gene conversion, and this occurs in a clonal population, not through lateral gene transfer between strains. The chapter on relapsing-fever species in the first edition was necessarily short: information about genetics of these organisms was limited. The agents of relapsing fever and Lyme disease are spirochetes, a separate group of eubacteria that are as different from gram-negative bacteria as they are from gram-positive bacteria or cyanobacteria. Although humans infected with a relapsing fever may become seriously ill and die, most infections of the usual vertebrate hosts for these microorganisms produce a mild illness. Clearly the bacterial examples of multiphasic antigenic variation of this chapter fall in the category of programmed rearrangements. Maenwhile, for relapsing fever spirochetes and gonococci at least, the process that varies expression among a repertoire of alleles is not as tidy and efficient as occurs in other programmed rearrangement systems, notably, yeast mating- type switches and the several examples of DNA inversions.

Citation: Barbou A. 2002. Antigenic Variation by Relapsing Fever Borrelia Species and Other Bacterial Pathogens, p 972-994. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch41

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Outer Membrane Proteins
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Genetic Elements
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Integral Membrane Proteins
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Type IV Pili
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Figures

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Figure 1

Single spirochete in a Wright-stained blood smear from a patient with tick-borne relapsing fever.

Citation: Barbou A. 2002. Antigenic Variation by Relapsing Fever Borrelia Species and Other Bacterial Pathogens, p 972-994. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch41
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Image of Figure 2
Figure 2

Case of relapsing fever. The patient was exposed to ticks during week −1 and became infected with The first episodes of fever began during week 1. The temperature curves of the patient are shown; “x” marks indicate the temperature readings. Possible serotypes of that could be recovered from the patient at the time of fever peaks are shown above. In order of appearance the serotypes were white, gray, hatched, and black.

Citation: Barbou A. 2002. Antigenic Variation by Relapsing Fever Borrelia Species and Other Bacterial Pathogens, p 972-994. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch41
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Image of Figure 3
Figure 3

Neighbor-joining phylogenetic relationships of genes of and with an gene of as the outgroup. The tree was based on data reported by Rich et al. ( ).

Citation: Barbou A. 2002. Antigenic Variation by Relapsing Fever Borrelia Species and Other Bacterial Pathogens, p 972-994. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch41
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Image of Figure 5
Figure 5

Partial physical maps of linear plasmids lp28-1, lp32, and lp28-2 of containing the expressed gene, the silent gene, and several other silent (dark-gray arrows) and (black arrows) genes. Previous designations for the plasmids are shown in parentheses ( ). The right arm of plasmid lp28-1 contains the hairpin telomere. The family membership of genes is indicated by adjoining α, β, δ, and γ symbols. The maps also show the location of genes that are homologous to plasmid replication and partition genes (light gray arrows without asterisks) of ( ), whose gene families' numbers are given in tilted boxes. The light-gray arrows with asterisks are partial sequences homologous to a putative transposase (see text). The striped vertical rectangles indicate the positions of the DHS; DHS inside single quotation marks indicates a partial sequence. The gray bars above each map refer to the regions of the plasmids that are shown in sequence detail in Fig. 6

Citation: Barbou A. 2002. Antigenic Variation by Relapsing Fever Borrelia Species and Other Bacterial Pathogens, p 972-994. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch41
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Figure 6

Nucleotide alignment of the 5′ends of the genes of expressed (7E) and of silent (7S), (21S), (36S), (6S), (13S), and (26S). The promoter region of 7E and upstream regions of the silent loci are also aligned. The locations of the sequences on the plasmids are shown in Fig. 5 . The entire 7E sequence is highlighted in gray. Those positions that are identical to the 7E sequence are also highlighted. The start codon is shown in white text on a black background. The location of the RBS is indicated. Selected palindromes of four or six bases are underlined. “+1” indicates the transcriptional start site ( ).

Citation: Barbou A. 2002. Antigenic Variation by Relapsing Fever Borrelia Species and Other Bacterial Pathogens, p 972-994. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch41
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Figure 7

Four mechanisms for serotype switches by The different mechanisms are discussed in the text. indicates the promoter and location of the expression site; an overhead arrow shows whether the gene is active and the direction of transcription. The or gene at this location determines the phenotype of the cell. The linear plasmid-borne or genes are indicated by boxes in solid colors (white, light gray, medium gray, dark gray, and black). The rest of the plasmid sequences are shown by patterns. In mechanism 2 a deletion by direct repeats (small horizontal bars) occurs and results in a nonreplicative circle. In mechanism 3 the suspected donor sequences for templated partial gene conversions are shown. The vertical arrows indicate the changes of one or two linear plasmids with each type of switch.

Citation: Barbou A. 2002. Antigenic Variation by Relapsing Fever Borrelia Species and Other Bacterial Pathogens, p 972-994. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch41
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Figure 4

Unrooted neighbor-joining phylogenetic tree of the α, β, δ, and γ subfamilies of genes of The locations on the trees of selected relapse sequences are shown (Barbour et al., submitted).

Citation: Barbou A. 2002. Antigenic Variation by Relapsing Fever Borrelia Species and Other Bacterial Pathogens, p 972-994. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch41
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Figure 8

(A) Full-length physical maps of four linear plasmids of containing expressed and silent alleles of and genes. The estimated lengths of the different plasmids are indicated to the right of the plasmid names. The locations of different and genes are indicated below the maps. The expressed promoter and the direction of transcription are indicated by and an arrow, respectively. Selected sites for the following restriction enzymes (with abbreviations in parentheses) are indicated: HI (B), I (C), RI (E), R47 (E), RV (Ev), II (G), dIII (H), I (P), II (V), I (Sa), I (S), F1 (Sr), I (Sp), and I (X). Modified from a figure in reference . Regions with the same pattern or shade have highly similar or identical sequences. (B) Matrix comparison of and and their downstream sequences. A two-bytwo matrix was performed on selected sequences shown in panel A. The axis displays and the downstream and (partial) genes; the axis displays and the downstream and (partial) genes. The diagonal lines represent windows with a match of at least 15 out of 20 nucleotides. Only contiguous matches of more than 50 bp are shown. Modified from a figure in reference .

Citation: Barbou A. 2002. Antigenic Variation by Relapsing Fever Borrelia Species and Other Bacterial Pathogens, p 972-994. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch41
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Figure 9

Organization of the locus and selected loci of the gene in one isolate of strain MSII ( ) of (A) and hypothetical recombinations between representative sequences and a locus (B). (A) genes are indicated by white boxes; the gray and block boxes indicate the RS1 and I/I repeats, respectively. (B) variable cassettes are designated by patterns or solid colors. To the left of each outcome of the gene conversion is shown a gonococcus with pili or without (outcome 3). The color of the bacterium refers to the pilin variant. In outcome 2 the partial gene conversion of the cassette results in a mosaic pilin gene. In outcome 3 the location of a stop codon in the reading frame is shown. The figure is modified from figures in reference .

Citation: Barbou A. 2002. Antigenic Variation by Relapsing Fever Borrelia Species and Other Bacterial Pathogens, p 972-994. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch41
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Image of Figure 10
Figure 10

Alignment of variable regions of pilin amino acid sequences. Sequences 307 to 320 are from reference , and sequences 938 to 943 are from . Highlighted positions (Pos) indicate identical residues that were present in at least 10 of the 19 sequences. Conserved cysteines are underlined. The numbering refers to the sequence of the prepilin of strain MSII ( ).

Citation: Barbou A. 2002. Antigenic Variation by Relapsing Fever Borrelia Species and Other Bacterial Pathogens, p 972-994. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch41
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Image of Figure 11
Figure 11

Schematic representation of the outcomes of inversions within the locus of The phenotype of the bacterium is indicated by a pattern and corresponds to the gene downstream of the promoter (). The arrow indicates the direction and extent of transcription. The black blocks at the 5′ends of the alleles are conserved sequences. The alleles are followed by nontranscribed repeats, which are shown as short gray boxes.

Citation: Barbou A. 2002. Antigenic Variation by Relapsing Fever Borrelia Species and Other Bacterial Pathogens, p 972-994. In Craig N, Craigie R, Gellert M, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington, DC. doi: 10.1128/9781555817954.ch41
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