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Chapter 14 : Control of Bacterial Diarrhea with Phages: Coverage and Safety Issues in Bacteriophage Therapy

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Abstract:

Antibiotics are frequently and uncritically used against diarrheal diseases in developing countries. While antibiotics are indicated against dysentery, antibiotics have only limited efficacy against a number of bacterial pathogens, including . With respect to their bacterial hosts, the vast majority of bacteriophages are species specific. A clear advantage of phages over antibiotics is that they target broad classes of bacteria and therefore kill not only the pathogen but also harmless or even beneficial commensals. Enteroinvasive and enterohemorrhagic (EHEC) strains are emerging but are still relatively rare isolates. diarrhea investigated in the community of urban Dhaka showed a lesser variety of pathotypes. Possibly due to the precarious hygiene situation in Dhaka, further compounded by regular floods, enterotoxigenic (ETEC) serotypes show a dynamic state and changes in serotype distribution have been documented over 2-year periods. The serological diversity of pathogenic is relevant for phage therapy since lipopolysaccharide (LPS), the physical determinant of the O serotype, is a preferred bacterial receptor structure recognized by T4 phages, a major group of professional virulent coliphages. The sequencing of T4-like coliphages defined additional subgroups of T4-like coliphages in addition to T4 proper. Comparative genomics of T4-like coliphages revealed a core of conserved genes represented by three contiguous blocks of structural genes and DNA replication genes.

Citation: Brüssow H. 2010. Control of Bacterial Diarrhea with Phages: Coverage and Safety Issues in Bacteriophage Therapy, p 273-295. In Sabour P, Griffiths M (ed), Bacteriophages in the Control of Food-and Waterborne Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555816629.ch14

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Figures

Image of FIGURE 1
FIGURE 1

Dot plot matrix of genome sequences from T4 coliphages. The alignment criterion for a dot was identity over a 40-bp DNA segment. With the exception of JSD1-4, all sequences represent complete genomes retrieved from the NCBI database. The dot plot matrix attributes in the following order the phages T4, RB14, and RB32 to a T4 subgroup; RB69 is a more distant relative of this subgroup; phages JS98, JS10, and JSD1-4 are members of the JS98 subgroup; RB49, JSE, and Phi1 belong to the RB49 subgroup; and RB43 is currently the only member of a further subgroup of T4-like coliphages. (Courtesy of S. Zuber, C. Barretto, and C. Ngom-Bru, Nestlé Research Center, Lausanne, Switzerland; reproduced with permission.)

Citation: Brüssow H. 2010. Control of Bacterial Diarrhea with Phages: Coverage and Safety Issues in Bacteriophage Therapy, p 273-295. In Sabour P, Griffiths M (ed), Bacteriophages in the Control of Food-and Waterborne Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555816629.ch14
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Image of FIGURE 2
FIGURE 2

Dot plot alignment of the genomes from the T4-like phages RB49 (y axis) and JSE (x axis). Each point indicates an exact match of 40 consecutive nucleotides between the two compared genomes using the NUCmer program. (Courtesy of S. Zuber, C. Barretto, and C. Ngom-Bru, Nestlé Research Center, Lausanne, Switzerland; reproduced with permission.)

Citation: Brüssow H. 2010. Control of Bacterial Diarrhea with Phages: Coverage and Safety Issues in Bacteriophage Therapy, p 273-295. In Sabour P, Griffiths M (ed), Bacteriophages in the Control of Food-and Waterborne Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555816629.ch14
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Image of FIGURE 3
FIGURE 3

Analysis of the DNA sequence differences between T4 coliphages JSE and RB49. Genome sequences were compared using the ACT software. On the axis the 166,418-bp-long JSE sequence is plotted. Each mark on the axis corresponds to a 10,000-bp distance. At the left side is JSE ORF_0001, corresponding to the RB49 gene. At the right side is JSE ORF_0277, corresponding to RB49 ORF_0274. (Top display) The spikes deviating upwards and downwards from the two horizontal lines represent insertions/deletions at the indicated genome position in JSE and RB49, respectively, i.e., gaps in the sequence alignment. The width of the spike indicates the length of the indel. The location of the indel is further indicated by the number of the JSE or RB49 ORF. ORFs that lack a complement in T4 have their number indicated in parentheses. If the ORF number is followed by * it identifies a putative homing endonuclease. If the spike is marked by # it indicates an intergenic region. The height of the downward or upward spikes has no meaning. (Bottom display) The bars on the bottom axis locate regions of DNA sequence diversity between JSE and RB49. The width of the bars indicates the length of the region showing sequence diversity. The regions of sequence diversity are further identified by the JSE ORF number; if the JSE ORF shares protein sequence identity with a T4 gene product, it is identified by the T4 gene symbol and so forth). The height of the bar has no meaning. (Courtesy of S. Zuber, C. Barretto, and C. Ngom-Bru, Nestlé Research Center, Lausanne, Switzerland; reproduced with permission.)

Citation: Brüssow H. 2010. Control of Bacterial Diarrhea with Phages: Coverage and Safety Issues in Bacteriophage Therapy, p 273-295. In Sabour P, Griffiths M (ed), Bacteriophages in the Control of Food-and Waterborne Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555816629.ch14
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Image of FIGURE 4
FIGURE 4

Dot plot alignment of the genomes from the T4-like phages JS98 (y axis) andJS10 (x axis). Each point indicates an exact match of 40 consecutive nucleotides between the two compared genomes using the NUCmer program. (Courtesy of S. Zuber, C. Barretto, and C. Ngom-Bru, Nestlé Research Center, Lausanne, Switzerland; reproduced with permission.)

Citation: Brüssow H. 2010. Control of Bacterial Diarrhea with Phages: Coverage and Safety Issues in Bacteriophage Therapy, p 273-295. In Sabour P, Griffiths M (ed), Bacteriophages in the Control of Food-and Waterborne Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555816629.ch14
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Image of FIGURE 5
FIGURE 5

Analysis of the DNA sequence differences between T4 coliphages JS10 and JS98. Genome sequences were compared using the ACT software. On the axis the 171,451-bp-long JS10 sequence is plotted. Each mark on the axis corresponds to a 10,000-bp distance. At the left side is JS10 ORF_0001, corresponding to the gene. At the right side is JS10 ORF_0265, corresponding to JS98 ORF_0266, the gene. (Top display) The spikes deviating upwards and downwards from the two horizontal lines represent insertions/deletions at the indicated genome position in JS10 and JS98, respectively, i.e., gaps in the sequence alignment. The width of the spike indicates the length of the indel. The location of the indel is further indicated by the number of the JS10 or JS98 ORF. ORFs that lack a complement in T4 are indicated in parentheses. If the ORF number is followed by * it identifies a putative homing endonuclease. If the spike is marked by # it indicates an intergenic region. If the ORFs share protein sequence identity with T4 phage they are identified by the T4 gene symbol and so forth). The height of the downward or upward spikes has no meaning. (Bottom display) The bars on the bottom axis locate regions of DNA sequence diversity between JS10 and JS98. The width of the bars indicates the length of the region showing sequence diversity. The regions of sequence diversity are further identified by the JS10 ORF number; if the JSE ORF shares protein sequence identity with a T4 gene product, it is identified by the T4 gene symbol and so forth). The height of the bar has no meaning. (Courtesy of S. Zuber, C. Barretto, and C. Ngom-Bru, Nestlé Research Center, Lausanne, Switzerland; reproduced with permission.)

Citation: Brüssow H. 2010. Control of Bacterial Diarrhea with Phages: Coverage and Safety Issues in Bacteriophage Therapy, p 273-295. In Sabour P, Griffiths M (ed), Bacteriophages in the Control of Food-and Waterborne Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555816629.ch14
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Image of FIGURE 6
FIGURE 6

Dot plot alignment of the genomes from the T4-like phages T4 (y axis) and RB32 (x axis). Each point indicates an exact match of 40 consecutive nucleotides between the two compared genomes using the NUCmer program. (Courtesy of S. Zuber, C. Barretto, and C. Ngom-Bru, Nestle Research Center, Lausanne, Switzerland; reproduced with permission.)

Citation: Brüssow H. 2010. Control of Bacterial Diarrhea with Phages: Coverage and Safety Issues in Bacteriophage Therapy, p 273-295. In Sabour P, Griffiths M (ed), Bacteriophages in the Control of Food-and Waterborne Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555816629.ch14
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