Ceramidase: Difference between revisions
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Due to its abundance in eukaryotic cell membranes and role in pathogen defense, pathogens have evolved mechanisms to use host ceramides for their own pathogenesis. Ceramide-rich membrane platforms on human-epithelial cells serve as sites for the attachment and invasion of bacterial pathogens such as ''Neisseria gonorrhoeae''. ''Pseudomonas aeruginosa'' is capable of detecting host-derived sphingosine, resulting in activation of ''P. aeruginosa'' sphingosine-responsive genes. The products of ''P. aeruginosa'' sphingosine-responsive genes are used for the detoxification of sphingosine, as well as its production from other host-derived sphingolipids, making ''P. aeruginosa'' sphingosine tolerant. Loss of ''P. aeruginosa'' sphingosine-responsive genes results in the inability of the bacteria to survive in the presence of sphingosine ''in vitro'' or in the murine lung. CerN is one of the proteins encoded by ''P. aeruginosa'' sphingosine-responsive genes used for the production of sphingosine from ceramide, with the added ability of functioning as a ceramide synthase.<ref name="Okino">PMID:9603946</ref><ref name="Reverse">PMID:10832092</ref> It has been hypothesized that the hydrolysis of host-membrane ceramide via CerN facilitates ''P. aeruginosa'' intracellular invasion, similar to other bacterial pathogens. CerN is also involved in ''P. aeruginosa'' [https://en.wikipedia.org/wiki/Biofilm/biofilm] production, a major virulence trait of the pathogen. Sphingosine production via CerN-mediated hydrolysis of host ceramide induces a biofilm formation at sites of infection, biofilm accumulation yields more ceramide hydrolysis, creating a positive-feedback loop for ''P. aeruginosa'' virulence. | Due to its abundance in eukaryotic cell membranes and role in pathogen defense, pathogens have evolved mechanisms to use host ceramides for their own pathogenesis. Ceramide-rich membrane platforms on human-epithelial cells serve as sites for the attachment and invasion of bacterial pathogens such as ''Neisseria gonorrhoeae''. ''Pseudomonas aeruginosa'' is capable of detecting host-derived sphingosine, resulting in activation of ''P. aeruginosa'' sphingosine-responsive genes. The products of ''P. aeruginosa'' sphingosine-responsive genes are used for the detoxification of sphingosine, as well as its production from other host-derived sphingolipids, making ''P. aeruginosa'' sphingosine tolerant. Loss of ''P. aeruginosa'' sphingosine-responsive genes results in the inability of the bacteria to survive in the presence of sphingosine ''in vitro'' or in the murine lung. CerN is one of the proteins encoded by ''P. aeruginosa'' sphingosine-responsive genes used for the production of sphingosine from ceramide, with the added ability of functioning as a ceramide synthase.<ref name="Okino">PMID:9603946</ref><ref name="Reverse">PMID:10832092</ref> It has been hypothesized that the hydrolysis of host-membrane ceramide via CerN facilitates ''P. aeruginosa'' intracellular invasion, similar to other bacterial pathogens. CerN is also involved in ''P. aeruginosa'' [https://en.wikipedia.org/wiki/Biofilm/biofilm] production, a major virulence trait of the pathogen. Sphingosine production via CerN-mediated hydrolysis of host ceramide induces a biofilm formation at sites of infection, biofilm accumulation yields more ceramide hydrolysis, creating a positive-feedback loop for ''P. aeruginosa'' virulence. | ||
<ref name="Complex">PMID:15289826</ref> <ref name="Seitz">PMID:25720061</ref> | |||
== Relevance == | == Relevance == | ||