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Chapter 9 : Virulence-Linked Bacteriophages of Pathogenic Vibrios

Authors: Brigid M. Davis1, Matthew K. Waldor1
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Affiliations: 1: Department of Microbiology, Tufts University School of Medicine, and Howard Hughes Medical Institute, Boston, MA 02111
Content Type: Monograph
Publication Year: 2005

Category: Bacterial Pathogenesis; Microbial Genetics and Molecular Biology

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Abstract:

This chapter focuses on the bacteriophages of pathogenic vibrios, particularly those that have been found to contribute directly to bacterial virulence. These phages primarily target ; however, a virulence-associated phage found in is also discussed briefly. O139 appears to have evolved from an O1 El Tor strain that acquired a new cassette of genes for O antigen production. Whether the emergence of O139 as a widespread etiologic agent of cholera marks the beginning of a new, eighth cholera pandemic is being debated. The 5’ end of the prophage (-2.4 kb) is known as the RS region. It encodes proteins needed for phage gene regulation (RstR), phage replication (RstA), and phage DNA integration (RstB). Genetic studies indicate that at least two protein complexes are used by CTXφ to infect . Toxin-coregulated pilus (TCP), a homopolymer of TcpA, is thought to be CTXφ’s primary receptor. A hybrid Fd phage that displays the N-terminal and central domains of pIII on its surface was able to infect , suggesting that pIII is the only CTXφ protein that is needed for normal recognition and infection of its host. Studies of the lysogenic filamentous phage have yielded knowledge of new types of virus-host interactions. The authors anticipate that future studies of CTXφ will provide additional examples of how a virus and its host can coevolve in a symbiotic fashion. Furthermore, it seems likely that future studies of other pathogenic vibrios will uncover new bacteriophages that influence pathogenicity.

Citation: Davis B, Waldor M. 2005. Virulence-Linked Bacteriophages of Pathogenic Vibrios, p 187-205. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch9
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Virulence-Linked Bacteriophages of Pathogenic Vibrios
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Citation: Davis B, Waldor M. 2005. Virulence-Linked Bacteriophages of Pathogenic Vibrios, p 187-205. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch9
/content/10.1128/9781555816506.chap9.fig9-1
FIGURE 1

(Top) Schematic diagram of the CTXϕ genome, drawn roughly to scale.Arrows show genes and the direction of transcription. Bent arrows represent the , , and promoters. Solid triangles represent the 15-bp repeats found at each end of the prophage. Protein functions are indicated underneath the genes.The overall organization of the CTXϕ genome is similar to those of other filamentous phages from species and of filamentous phages from . (Middle) Graph of the G+C content of the CTXϕ genome, calculated by use of a 100-bp sliding window.The G+C contents of and differ the most dramatically from the average %G+C.The G+C contents of and the promoter were calculated for . (Bottom) Schematic diagram of RS1, a satellite phage related to CTXϕ.

10.1128/9781555816506/fig9-1_thmb.gif
10.1128/9781555816506/fig9-1.gif
Image of FIGURE 1
FIGURE 1

(Top) Schematic diagram of the CTXϕ genome, drawn roughly to scale.Arrows show genes and the direction of transcription. Bent arrows represent the , , and promoters. Solid triangles represent the 15-bp repeats found at each end of the prophage. Protein functions are indicated underneath the genes.The overall organization of the CTXϕ genome is similar to those of other filamentous phages from species and of filamentous phages from . (Middle) Graph of the G+C content of the CTXϕ genome, calculated by use of a 100-bp sliding window.The G+C contents of and differ the most dramatically from the average %G+C.The G+C contents of and the promoter were calculated for . (Bottom) Schematic diagram of RS1, a satellite phage related to CTXϕ.

Citation: Davis B, Waldor M. 2005. Virulence-Linked Bacteriophages of Pathogenic Vibrios, p 187-205. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch9
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/content/10.1128/9781555816506.chap9.fig9-2
FIGURE 2

Schematic representation of CTXϕ integration.The chromosomal integration site () recombines with the integration site in pCTX () through short regions of homology (white rectangles; equivalent to the solid triangles seen in Fig. 1 ).This process yields a single integrated prophage.

10.1128/9781555816506/fig9-2_thmb.gif
10.1128/9781555816506/fig9-2.gif
Image of FIGURE 2
FIGURE 2

Schematic representation of CTXϕ integration.The chromosomal integration site () recombines with the integration site in pCTX () through short regions of homology (white rectangles; equivalent to the solid triangles seen in Fig. 1 ).This process yields a single integrated prophage.

Citation: Davis B, Waldor M. 2005. Virulence-Linked Bacteriophages of Pathogenic Vibrios, p 187-205. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch9
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FIGURE 3

Arrangement of CTX prophage and RS1 DNA integrated in a variety of clinical isolates of . Most O1 El Tor biotype strains and O139 strains (all of those shown here) have CTXϕ DNA integrated into the large chromosome (chrI). Phage DNA is typically part of an array of tandemly integrated elements.We have found that strain N16961 has two copies of RS1 that flank a prophage rather than a single RS1 element downstream of the prophage, as was reported previously ( ). O1 classical biotype strains have CTXϕ DNA integrated into both chromosomes. Each chromosome has either a single prophage or an array of two truncated, fused prophages.

10.1128/9781555816506/fig9-3_thmb.gif
10.1128/9781555816506/fig9-3.gif
Image of FIGURE 3
FIGURE 3

Arrangement of CTX prophage and RS1 DNA integrated in a variety of clinical isolates of . Most O1 El Tor biotype strains and O139 strains (all of those shown here) have CTXϕ DNA integrated into the large chromosome (chrI). Phage DNA is typically part of an array of tandemly integrated elements.We have found that strain N16961 has two copies of RS1 that flank a prophage rather than a single RS1 element downstream of the prophage, as was reported previously ( ). O1 classical biotype strains have CTXϕ DNA integrated into both chromosomes. Each chromosome has either a single prophage or an array of two truncated, fused prophages.

Citation: Davis B, Waldor M. 2005. Virulence-Linked Bacteriophages of Pathogenic Vibrios, p 187-205. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch9
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FIGURE 4

Production of extrachromosomal CTXϕ DNA from a prophage array relies on a replicative process mediated by RstA. Phage DNA excision does not occur. Replication initiates at the origin of replication, which lies near the 3′ end of . As the replication complex moves along the phage DNA template, it displaces a single strand of the phage genome and replaces it with a newly synthesized strand. Replication continues past the end of the prophage, into the adjacent element downstream (in this case, RS1). Replication terminates at the origin of replication of the downstream element. A single-stranded hybrid phage genome, containing DNA from both the upstream and downstream elements in the array, is then released.

10.1128/9781555816506/fig9-4_thmb.gif
10.1128/9781555816506/fig9-4.gif
Image of FIGURE 4
FIGURE 4

Production of extrachromosomal CTXϕ DNA from a prophage array relies on a replicative process mediated by RstA. Phage DNA excision does not occur. Replication initiates at the origin of replication, which lies near the 3′ end of . As the replication complex moves along the phage DNA template, it displaces a single strand of the phage genome and replaces it with a newly synthesized strand. Replication continues past the end of the prophage, into the adjacent element downstream (in this case, RS1). Replication terminates at the origin of replication of the downstream element. A single-stranded hybrid phage genome, containing DNA from both the upstream and downstream elements in the array, is then released.

Citation: Davis B, Waldor M. 2005. Virulence-Linked Bacteriophages of Pathogenic Vibrios, p 187-205. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch9
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