Abstract
Acid sphingomyelinase (ASM) is a key enzyme in sphingolipid metabolism that converts sphingomyelin to ceramide, thereby modulating membrane structures and signal transduction. Bacterial pathogens can manipulate ASM activity and function, and use host sphingolipids during multiple steps of their infection process. An increase in ceramides upon infection results in the formation of ceramide-enriched membrane platforms that serve to cluster receptor molecules and organize intracellular signaling molecules, thus facilitating bacterial uptake. In this review, we focus on how extracellular bacterial pathogens target ASM and modulate membrane properties and signaling pathways to gain entry into eukaryotic cells or induce cell death. We describe how intracellular pathogens interfere with the intralysosomal functions of ASM to favor replication and survival. In addition, bacteria utilize their own sphingomyelinases as virulence factors to modulate sphingolipid metabolism. The potential of ASM as a target for treating bacterial infections is also discussed.
Acknowledgments
The authors thank their respective laboratory members and researchers whose work has not been discussed in detail or reviewed elsewhere. The work presented here from Dr. Schubert-Unkmeir’s laboratory is supported by funding from the German research foundation (Funder ID: 10.13039/501100001659, grant nos. SCHU2394/2-1 and SCHU2394/2-2).
Conflict of interest statement: The authors declare that there are no conflicts of interest.
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©2018 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Highlight: sphingolipids in infectious biology and immunology
- Sphingolipids in early viral replication and innate immune activation
- The function of sphingomyelinases in mycobacterial infections
- The role of acid sphingomyelinase and modulation of sphingolipid metabolism in bacterial infection
- The neutral sphingomyelinase 2 in T cell receptor signaling and polarity
- Click reactions with functional sphingolipids
- Sphingolipids in inflammatory hypoxia
- CD4+ Foxp3+ regulatory T cell-mediated immunomodulation by anti-depressants inhibiting acid sphingomyelinase
- Pathological manifestations of Farber disease in a new mouse model
- Pulmonary infection of cystic fibrosis mice with Staphylococcus aureus requires expression of α-toxin
- Minireview
- Roles of the nucleotide exchange factor and chaperone Hsp110 in cellular proteostasis and diseases of protein misfolding
- Research Articles/Short Communications
- Proteolysis
- The two cathepsin B-like proteases of Arabidopsis thaliana are closely related enzymes with discrete endopeptidase and carboxydipeptidase activities
Articles in the same Issue
- Frontmatter
- Highlight: sphingolipids in infectious biology and immunology
- Sphingolipids in early viral replication and innate immune activation
- The function of sphingomyelinases in mycobacterial infections
- The role of acid sphingomyelinase and modulation of sphingolipid metabolism in bacterial infection
- The neutral sphingomyelinase 2 in T cell receptor signaling and polarity
- Click reactions with functional sphingolipids
- Sphingolipids in inflammatory hypoxia
- CD4+ Foxp3+ regulatory T cell-mediated immunomodulation by anti-depressants inhibiting acid sphingomyelinase
- Pathological manifestations of Farber disease in a new mouse model
- Pulmonary infection of cystic fibrosis mice with Staphylococcus aureus requires expression of α-toxin
- Minireview
- Roles of the nucleotide exchange factor and chaperone Hsp110 in cellular proteostasis and diseases of protein misfolding
- Research Articles/Short Communications
- Proteolysis
- The two cathepsin B-like proteases of Arabidopsis thaliana are closely related enzymes with discrete endopeptidase and carboxydipeptidase activities