Chapter 5 : Pneumolysin and Other Virulence Proteins

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(the pneumococcus) makes a range of molecules that can be considered virulence factors. The organism also makes a range of protein virulence factors, including surface proteins (choline-binding proteins, LPXTG-anchored proteins, and lipoproteins) as well as a range of enzymes (superoxide dismutase, NADH oxidase, zinc metalloproteinases) and the pore-forming toxin pneumolysin (PLY). This chapter focuses on PLY and some of the other protein virulence factors of the pneumococcus. The toxin can have other effects on cells and has been shown to affect the production of proinflammatory mediators such as tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and IL-6. It was shown that PLY contributes to neuronal damage in a rabbit model of pneumococcal meningitis. An effect of PLY on calcium levels has also been demonstrated in neuroblastoma cells, in which purified PLY was shown to induce apoptosis in a calcium-dependent manner. The changes in calcium levels were due to pore formation by the toxin rather than opening of voltage-gated Ca channels. This study also showed that mitogen-activated protein kinase p38 was important in PLY-induced cell death. The overall virulence gene content of the pneumococcus will presumably dictate its ability to cause disease.

Citation: Mitchell T. 2004. Pneumolysin and Other Virulence Proteins, p 61-74. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch5

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