Phase and Antigenic Variation in Bacteria

Abstract

Phase and antigenic variation result in a heterogenic phenotype of a clonal bacterial population, in which individual cells either express the phase-variable protein(s) or not, or express one of multiple antigenic forms of the protein, respectively. This form of regulation has been identified mainly, but by no means exclusively, for a wide variety of surface structures in animal pathogens and is implicated as a virulence strategy. This review provides an overview of the many bacterial proteins and structures that are under the control of phase or antigenic variation. The context is mainly within the role of the proteins and variation for pathogenesis, which reflects the main body of literature. The occurrence of phase variation in expression of genes not readily recognizable as virulence factors is highlighted as well, to illustrate that our current knowledge is incomplete. From recent genome sequence analysis, it has become clear that phase variation may be more widespread than is currently recognized, and a brief discussion is included to show how genome sequence analysis can provide novel information, as well as its limitations. The current state of knowledge of the molecular mechanisms leading to phase variation and antigenic variation are reviewed, and the way in which these mechanisms form part of the general regulatory network of the cell is addressed. Arguments both for and against a role of phase and antigenic variation in immune evasion are presented and put into new perspective by distinguishing between a role in bacterial persistence in a host and a role in facilitating evasion of cross-immunity. Finally, examples are presented to illustrate that phase-variable gene expression should be taken into account in the development of diagnostic assays and in the interpretation of experimental results and epidemiological studies

Variable expression of immunoreactive surface proteins of Propionibacterium acnes

“…This is likely to have arisen from a second start site downstream of the frameshifted signal sequence. The comparison of the sequence data between isolates, particularly in the repeat regions of the proteins, is highly suggestive of insertions and deletions having arisen by slipped-strand mispairing as found in other pathogenic bacteria (van der Woude & Baumler, 2004). Therefore the molecular mass heterogeneity could also have been generated by within-clone variation.…”

Sialic acid utilization by bacterial pathogens

“…Some pathogens, such as Neisseria spp., H. influenzae and C. jejuni, regulate expression of cellsurface features by stochastic genetic mechanisms relying on rapid and reversible ON to OFF switching of the expression of key biosynthetic genes, the so-called 'phase variation ' (van der Woude & Baumler, 2004). Phase variation also modulates O-acetylation of the PSA capsule of E. coli K1 (Deszo et al, 2005;Bergfeld et al, 2007).…”

Diverse Functions of Restriction-Modification Systems in Addition to Cellular Defense

“…Phase variation is the heritable, interchangeable, and high-frequency on-or-off switching of transcription mediated by several mechanisms (173,174). Host-adapted bacterial pathogens frequently use phase variation to generate diversity in antigenic surface structures such as pili, capsules, lipopolysaccharides, and flagella (174,175).…”

“…Host-adapted bacterial pathogens frequently use phase variation to generate diversity in antigenic surface structures such as pili, capsules, lipopolysaccharides, and flagella (174,175). Pathogenic bacteria use the phase variability of gene expression to evade the host immune system.…”