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Volume 163, Issue 10

Expression of matrix metalloproteinases in and their role in invasion of the central nervous system Free

Abstract

is a free-living amoeba found in freshwater lakes and ponds and is the causative agent of primary amoebic meningoencephalitis (PAM), a rapidly fatal disease of the central nervous system (CNS). PAM occurs when amoebae attach to the nasal epithelium and invade the CNS, a process that involves binding to, and degradation of, extracellular matrix (ECM) components. This degradation is mediated by matrix metalloproteinases (MMPs), enzymes that have been described in other pathogenic protozoa, and that have been linked to their increased motility and invasive capability. These enzymes also are upregulated in tumorigenic cells and have been implicated in metastasis of certain tumours. In the present study, experiments linked MMPs functionally to the degradation of the ECM. Gelatin zymography demonstrated enzyme activity in whole cell lysates, conditioned media and media collected from invasion assays. Western immunoblotting indicated the presence of the metalloproteinases MMP-2 (gelatinase A), MMP-9 (gelatinase B) and MMP-14 [membrane type-1 matrix metalloproteinase (MT1-MMP)]. Highly virulent mouse-passaged amoebae expressed higher levels of MMPs than weakly virulent axenically grown amoebae. The functional relevance of MMPs in media was indicated through the use of the MMP inhibitor, 1,10-phenanthroline. The collective results suggest that MMPs play a critical role in invasion of the CNS and that these enzymes may be amenable targets for limiting PAM.

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Keyword(s): amoeba , invasion , matrix metalloproteinase , MMP and N. fowleri
© 2017 The Authors
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2017-10-01
2024-04-25
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Expression of matrix metalloproteinases in Naegleria fowleri and their role in invasion of the central nervous system
Microbiology 163, 1436 (2017); https://doi.org/10.1099/mic.0.000537
/content/journal/micro/10.1099/mic.0.000537
/content/journal/micro/10.1099/mic.0.000537
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