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Clinical Microbiology Reviews, July 2004, p. 581-611, Vol. 17, No. 3
0893-8512/04/$08.00+0     DOI: 10.1128/CMR.17.3.581-611.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Phase and Antigenic Variation in Bacteria

Marjan W. van der Woude1* and Andreas J. Bäumler2

Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6076,1 Department of Medical Microbiology and Immunology, College of Medicine, Texas A & M University System Health Science Center, College Station, Texas 77843-11142

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.

* Corresponding author. Mailing address: Department of Microbiology, University of Pennsylvania, 202A Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104-6076. Phone: (215) 573-4104. Fax: (215) 573-4184. E-mail mvdwoude{at}mail.med.upenn.edu.

Clinical Microbiology Reviews, July 2004, p. 581-611, Vol. 17, No. 3
0893-8512/04/$08.00+0     DOI: 10.1128/CMR.17.3.581-611.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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