Chapter 20 : Apoptosis and Enteric Bacterial Infections

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Apoptosis and Enteric Bacterial Infections, Page 1 of 2

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This chapter summarizes the numerous mechanisms that enteropathogenic bacteria use to induce apoptosis in host cells. It focuses on bacterium induced cell death by three enteric pathogens: , , and . Despite the many mechanistic commonalities shared by these enteric bacteria, the outcome of infection differs considerably. The aim of the chapter is to illustrate how each of the three microbes manages to manipulate the relationship between apoptotic events and pathogenesis according to its individual needs. The integrity of the cell membrane is compromised, resulting in leakage of intracellular contents. In contrast, apoptosis is characterized by cell shrinkage, chromatin condensation, and often loss of contact with adjacent cells. Two of the best characterized cell death receptors are the tumor necrosis factor alpha (TNF-α) receptor (TNF-R) and Fas. These two receptors need to be trimerized in order to signal. and enterohemorrhagic (EHEC), which cause severe diarrheal diseases and hemolytic uremic syndrome (HUS), produce A-B type toxins, called Shiga toxin and Shiga-like toxins or verotoxins, respectively. In enteric infections, toxin-mediated apoptosis preferentially targets epithelial cells, while the bacterial effector proteins interfering with the endogenous death machinery of the cell appear to selectively affect macrophages. The first encounter between bacteria and phagocytes occurs subsequent to ’s traversing the colonic barrier through specialized epithelial cells, called M cells. Many pathogens not only use M cells as their port of entry to the intestinal mucosa, but also have designed strategies to evade elimination by professional phagocytes.

Citation: Raupach B, Zychlinsky A. 2003. Apoptosis and Enteric Bacterial Infections, p 367-384. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch20

Key Concept Ranking

Bacterial Proteins
Tumor Necrosis Factor alpha
Type III Secretion System
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TLR signaling cascades. Upon activation, TLR recruit the adaptor molecule MyD88, which can initiate two independent outcomes: apoptosis and transcriptional activation. Apoptosis is activated by the initial recruitment of the FADD protein, which recruits the regulatory Casp8. Recruitment of FADD also provokes the maturation of Casp1, which in turns cleaves pro-IL-1 to its active form. Alternatively, MyD88 can recruit IRAK, which through TRAF6 activates MKK and IKK. MKK can phosphorylate JNK, which activates the transcription factor AP-1. Alternatively, IKK phosphorylates and targets I-B (inhibitor of B) to the proteasome, allowing NF-B to migrate to the nucleus and initiate transcription.

Citation: Raupach B, Zychlinsky A. 2003. Apoptosis and Enteric Bacterial Infections, p 367-384. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch20
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Image of FIGURE 2

Transmission electron micrograph of lymphoid follicles infected with . Virulence of the wild-type strain M90T was assessed in the rabbit ligated ileal loop model. At 8 h post-infection, tissue samples were fixed and processed for transmission electron microscopy. Cells with apoptotic morphology were detected and contain intracellular bacteria (arrowhead). Bar, 1 m. (Reprinted from reference .)

Citation: Raupach B, Zychlinsky A. 2003. Apoptosis and Enteric Bacterial Infections, p 367-384. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch20
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Image of FIGURE 3

Casp1 activation by results in inflammation and cell death. After internalization by macrophages, escapes from the phagosome into the cytoplasm of the host cell where it secretes the virulence factor IpaB via a type III secretion system. As a consequence of the direct interaction between IpaB and Casp1, this cysteine protease initiates both an apoptotic cascade leading to cell death and processing and release of the proinflammatory cytokines IL-1 and IL-18, resulting in inflammation.

Citation: Raupach B, Zychlinsky A. 2003. Apoptosis and Enteric Bacterial Infections, p 367-384. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch20
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Image of FIGURE 4

Pathways of -induced cell death in macrophages. (A) SPI1-dependent cell death occurs rapidly after infection with invasive strains and depends on the interaction between Casp1 and the bacterial effector SipB. As for , SipB-mediated activation of Casp1 leads to the processing of proinflammatory cytokines and cell death. (B) An SPI1-independent mechanism of -induced cell death is observed later after infection. The exact sequence of events leading to macrophage killing is still unclear; however, delayed cell death depends on the -regulated pathogenicity island SPI2 and in part on Casp1.

Citation: Raupach B, Zychlinsky A. 2003. Apoptosis and Enteric Bacterial Infections, p 367-384. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch20
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Image of FIGURE 5

induces cell death by inhibition of survival pathways and by inducing apoptosis. delivers the effector molecule YopJ into the host cell via type III secretion. YopJ blocks activation of the superfamily of MAPK kinases, thus inactivating both MAPK signaling and NF-B activity. Inhibition of these pathways prevents the cell from producing cytokines and antiapoptotic factors. In addition, can activate the cell death machinery. Whether this process directly involves YopJ is unclear.

Citation: Raupach B, Zychlinsky A. 2003. Apoptosis and Enteric Bacterial Infections, p 367-384. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch20
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