Chapter 12 : Shiga Toxin-Producing

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This chapter discusses the emergence and impact of shiga toxin-producing (STEC) in human disease, the biology of the Shiga toxins (Stx) family, and approaches to diagnosis, treatment, and prevention of infection with STEC. The occurrence of the seminal STEC outbreaks highlighted the need to implement laboratory methods to readily detect O157:H7. Although early characterization of STEC strains was made possible by Whittam’s multilocus enzyme electrophoresis (MLEE) method, genetic techniques now allow comparison of strains at the nucleotide level. The current model of the predominant pathway by which Stx intoxicates sensitive cells is as follows: (i) the B pentamer of holotoxin binds to Gb within lipid rafts; (ii) the entire receptor-holotoxin complex is endocytosed; (iii) the complex moves by retrograde transport to the Golgi and then to the endoplasmic reticulum; and (iv) the A subunit is released into the cytoplasm, where it targets the ribosome. Although transduction of stx genes into via bacteriophages was crucial to the emergence of STEC, the biology of these toxin-converting phages also contributes significantly to the degree of toxin expression and hence the virulence exhibited by STEC. Although the pathogenicity of various STEC strains that synthesize different types of Stx2 cannot be compared directly because the strains are not isogenic, the authors have found that an O91 strain that produces Stx2 is not virulent in the streptomycin-treated mouse model for STEC infection, whereas O91 strains that produce Stx2d-activatable are highly virulent in those mice.

Citation: Teel L, Melton-Celsa A, O’Brien A. 2011. Shiga Toxin-Producing , p 199-223. In Walk S, Feng P (ed), Population Genetics of Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555817114.ch12
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Image of Figure 1.
Figure 1.

Ribbon diagram of the Stx2 crystal structure. The A subunit is depicted in black while the five B subunits are shown in alternating light and dark gray. This image (Protein Data Bank ID: 1R4P) was generated with Protein Workshop 3.6.

Citation: Teel L, Melton-Celsa A, O’Brien A. 2011. Shiga Toxin-Producing , p 199-223. In Walk S, Feng P (ed), Population Genetics of Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555817114.ch12
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Image of Figure 2.
Figure 2.

Stx expression is under the control of multiple genetic elements. Expression of and the lambdoid late genes is repressed during lysogeny by the binding of the phage repressor CI to sites between the early left and right promoter regions ( and ). Upon phage induction, the CI repressor is cleaved and the N antiterminator is transcribed from . N facilitates transcription through numerous terminator sequences ( ), such that the Q antiterminator is expressed. When Q binds , the ′ promoter is active and transcription proceeds through the operon and on through the (holin) and (endolysin) genes further downstream. Thus Q antitermination and transcription originating at ′ contributes most strongly to Stx1 and Stx2 production upon phage induction. Stx1 expression is also partially mediated by an iron-repressed (Fur) promoter, . Very low levels of Stx1 are produced when the bacteria are grown in high iron conditions in the absence of phage induction, and in low iron conditions Stx1 expression from the promoter is enhanced. Low levels of transcription originating at occur in the absence of phage induction independent of iron concentration. Arrows denote the length of transcripts with and without antitermination. The relative strength of each promoter is indicated by the thickness of the transcript arrows. Based on diagrams by Wagner et al. ( ) and reprinted with permission of the publisher.

Citation: Teel L, Melton-Celsa A, O’Brien A. 2011. Shiga Toxin-Producing , p 199-223. In Walk S, Feng P (ed), Population Genetics of Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555817114.ch12
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