Chapter 24 : Phase Variation

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This chapter focuses on phase variation (PV) , which because of its ON/OFF nature has broader biological implications than antigenic variation. The diverse mechanisms of PV and additional regulation impact on how PV can benefit the bacterial population and how stress can affect PV. Although research into PV focuses on pathogens, as does this chapter, it should be noted that PV also occurs in commensals and environmental isolates. The complexity of analyses of competition experiments in animal hosts was highlighted by a study of colonization of chicks by . In this study two strains were used that were identical but distinguishable by a mere 40-bp nucleotide tag. DNA methylation is known to control gene expression, and recent research suggests that at least some of these phase varying methyltransferases may control the expression of large numbers of genes in so called phasevarions. The availability of genome sequences of hundreds of pathogens has facilitated the identification of (putative) PV that arises from slipped strand mispairing (SSM) and conservative site specific recombination (CSSR) because these have signature DNA sequences or proteins associated with them. This has led to the identification of very high numbers of putative phenotypic variants.

Citation: van der Woude M, Broadbent S. 2011. Phase Variation, p 399-416. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch24
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Image of Figure 1.
Figure 1.

Schematic representation of regions affected by slipped strand mispairing (SSM). The five alternative positions relative to the gene at which SSMs have been shown to lead to PV are shown on the diagram. (A) Transcription factor binding site. (B) RNA polymerase binding site (-10 and -35). (C) Region between promoter and transcription start site. (D) 5” UTR or Shine-Dalgarno ribosome binding site (SD). (E) Coding sequence. Transcription factors (TF; black circle), RNA polymerase (RNApol), mRNA transcript, ribosome (R; black shape), and polypeptide are all indicated. The transcription factor binding site (TF BS) and RNApol binding site (-10 and -35) and Shine Dalgarno ribosome binding site (SD) are indicated by black boxes. The transcription start site is indicated by the thin black arrow. The coding sequence is indicated by a thick black arrow. Double-headed black arrows (SSM) indicate locations where short sequence repeats have been shown to cause PV. Doubleheaded white arrows indicate the consequences of SSM for the factors shown on the diagram. The figure is not to scale.

Citation: van der Woude M, Broadbent S. 2011. Phase Variation, p 399-416. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch24
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Image of Figure 2.
Figure 2.

Mechanisms of PV by conservative site specific recombination (CSSR). Left and right inverted repeats are indicated by boxes (IRL and IRR) and are shown upside down following inversion. Both the ON and OFF orientations are shown for both examples. Transcription start sites are indicated by small black arrows and are labeled according to the gene they relate to. Coding sequences are indicated by thick black arrows and are labeled with the gene name. Neither diagram is to scale. See text for details. (A) PV of type I fimbriae () in . The invertible promoter element between the inverted repeats IRR and IRL (squares) is shown, as well as the genes encoding the two recombinases ( and ) and the structural gene (). Regulators are shown and mode of action for the genes they affect. However, binding sites and regulatory mechanisms for these regulators are not shown. (B) PV of in . The promoter, coding sequence, and inverted repeat region within the transcript are shown. Transcription is indicated by the white arrow and the two alternative transcripts are shown. The intrinsic transcriptional terminator is shown as a hairpin loop.

Citation: van der Woude M, Broadbent S. 2011. Phase Variation, p 399-416. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch24
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Image of Figure 3.
Figure 3.

Methylation-dependent PV. The methylation state and transcription factor binding are shown for both the ON and OFF states. Open circles indicate unmethylated GATC sequences; closed circles indicate methylated GATC sequences. Transcription start sites are indicated by small black arrows and the RNA polymerase binding sites (-10 and -35) are shown. Coding sequences are indicated by thick black arrows and are labeled with the gene name. Neither diagram is to scale. For clarity, proteins are shown on a single face of the DNA; however, this is does not indicate the position at which they bind. (A) Dam- and OxyR-dependent PV of . The three GATC (Dam target) sequences are shown. The binding site for OxyR within the promoter is indicated (BS), as are OxyR, Dam methylase, and RNA polymerase. (B) Dam- and Lrp-dependent PV of P pili (). The transcription factors Lrp, PapB, and CAP are shown as are the two GATC sequences. Epistatic repression of expression in the ON state is shown, but binding sites and mechanisms for these regulators are not indicated.

Citation: van der Woude M, Broadbent S. 2011. Phase Variation, p 399-416. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch24
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