Pathogen escape from host immunity by a genome program for antigenic variation

Abstract

The vector-borne bacterium Borrelia hermsii, a relapsing fever agent, switches gene expression of a surface protein between different antigenic variants, thereby causing sequential waves of immune escape within hosts and increasing the likelihood of transmission. Analogous programmed systems of antigenic variation occur in African trypanosomes and Plasmodium falciparum. In these examples, switch rates to individual variants differ over a wide range. We studied how B. hermsii determines switch rates in two experimental infections: one where variants were identified by specific antisera and one based on identification by DNA sequence. Unexpressed loci of variant antigens copy into a single expression site at rates determined by extragenic features of silent loci rather than similarity between coding sequences of variants at silent sites and the single expression site. Two elements, in particular, determine switch rates. One set of elements overlaps the 5 ends of the expressed gene and the silent loci; greater sequence identity between elements was associated with a higher switch rate. The second set of elements flanks the expression site on the 3 side and occurs at variable distances downstream from silent loci; the nearer an element to a silent locus, the greater the switch rate of that locus into the expression site. In combination, these two features of the genome provide a simple mechanism to modulate switch rate whereby silent loci form a hierarchy of switch rates into the expression site. Although the switching hierarchy causes changes in individual cells that are stochastic, ordering of variants within hosts is semipredictable.antibody ͉ Borrelia ͉ recombination ͉ relapsing fever ͉ vector-borne

Outer Membrane Protein Sequence Variation in Lambs Experimentally Infected with Anaplasma phagocytophilum

“…The cyclic rickettsemias observed suggest a mechanism by which the pathogen escapes the cellular and humoral immune responses by switching surface antigens and so being unrecognized for reappearance at a later stage of infection. It is known that tick-borne pathogens have the ability to persist in the body in order to be transmitted between hosts by feeding ticks (5,23,29,30). Earlier studies suggested that differential msp2(p44) expression is associated with host adaptive immunity (24).…”

Role of glycan synthesis in colonization of the mammalian gut by the bacterial symbiont Bacteroides fragilis

“…Thus, the capacity to produce multiple phase-variable capsular polysaccharides creates diverse populations with regard to surface architecture, including some that would be less susceptible to attack by deleterious products. Indeed, many pathogenic bacteria and parasites have evolved mechanisms by which they alter their surface antigenicity to persist in the host (26)(27)(28).…”

Oms38 Is the First Identified Pore-Forming Protein in the Outer Membrane of Relapsing Fever Spirochetes

“…Few membrane-spanning proteins are located in the outer membrane (35,55). The most abundant proteins in the RF outer membrane are the variable major proteins Vmp, lipoproteins that are expressed with different surface epitopes through antigenic variation (2,5,68,69).…”

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