Chapter 26 : Toxins of : Consensus and Controversy

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The bacterial agent of disease, , was presumed to require only two virulence factors: toxincoregulated pili (TCP) to colonize the human intestinal epithelium and cholera toxin (CT) to elicit diarrhea. This chapter covers each of the known cytotoxins of . Biopsies taken from cholera patients indicate that the intestinal epithelium remains intact during the infectious stage, although abnormal distention of the apical intracellular junctions has been observed. In the bone marrow macrophages, CT also inhibits production of nitric oxide (NO) by downregulating the synthesis of inducible nitric oxide synthase (iNOS). A significant role of CtxB in the inhibition of Th1 responses has been verified in vivo by investigators studying oral tolerance and autoimmunity. Treatment of mesenteric lymph node cells with CtxB for 48 h triggers apoptosis of about 75% of the CD8 T-cell population, a reaction that may occur through signaling by c-Myc based on observations with the related protein EtxB. When the immune system does successfully clear the infection, the concurrent dissemination by induction of diarrhea would be a secondary strategy allowing survival of the entire species. Additional controversy concerning the role of Zot in pathogenesis has arisen from the demonstration that Zot is essential for a function unrelated to toxinogenesis.

Citation: Fullner K. 2003. Toxins of : Consensus and Controversy, p 481-502. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch26
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Image of FIGURE 1

CT blocks innate and adaptive immune responses. As described in the text, CT or the subunit CtxB blocks multiple stages of the immune response during infection. The production of cytokines and NO by antigen-presenting cells downregulates the innate response. Antigen processing and the development of a Th1 adaptive immune response are inhibited. Evidence suggests that CtxB stimulates a Th2-type response.

Citation: Fullner K. 2003. Toxins of : Consensus and Controversy, p 481-502. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch26
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Image of FIGURE 2

Colinear genetic arrangement of bacteriophage f1 and CTX. Figure was drawn using MacVector 7.0 (Oxford Molecular Group, Madison, Wis.) based on the genomic sequences of El Tor N16961 (GenBank accession NC_002505 [ ]) and bacteriophage f1 (GenBank accession NC_001397 [ ]).

Citation: Fullner K. 2003. Toxins of : Consensus and Controversy, p 481-502. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch26
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Image of FIGURE 3

Schematic diagram of pI-like proteins. NBS is found at residues 8 to 15 in all proteins. Transmembrane domain (TM) and cytoplasmic amphipathic helix (+++) for f1 pI and pXI as in reference 46. Locations of TM for Zot, Pf1, and Pf3 are based on sequence analysis using DAS ( ), with (+++) indicating conservation of charge residues next to TM. Zonulin motif (ZM) of Zot protein represents an octapeptide shared between Zot and the human protein zonulin it is proposed to mimic ( ).

Citation: Fullner K. 2003. Toxins of : Consensus and Controversy, p 481-502. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch26
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Image of FIGURE 4

HA/P causes rounding and detachment of HEp-2 cells. Phase-images of 70% confluent monolayers of HEp-2 epithelial cells treated for 60 min with phosphate-buffered saline (left) or ammonium sulfate-precipitated supernatant fluids from a HA/P strain (middle) and an isogenic HA/P strain (right). Data previously presented as data not shown ( ).

Citation: Fullner K. 2003. Toxins of : Consensus and Controversy, p 481-502. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch26
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Image of FIGURE 5

Vacuolation of Vero cells treated for 2 h with HlyA-producing culture supernatant fluid in the presence of 100 nM concanamycin. Reproduced from reference 35 with permission.

Citation: Fullner K. 2003. Toxins of : Consensus and Controversy, p 481-502. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch26
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Image of FIGURE 6

Depolymerization of F-actin by RTX toxin. PtK2 cells were either treated for 60 min with phosphate-buffered saline (mock) or incubated with secreting RTX toxin. Cells were fixed and stained with fluorescently labeled phalloidin to visualize polymerized F-actin. Data previously reported as data not shown ( ).

Citation: Fullner K. 2003. Toxins of : Consensus and Controversy, p 481-502. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch26
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