Phospholipase C Mechanisms in Pseudomonas aeruginosa Pathogenesis
Summary
Pseudomonas aeruginosa employs a suite of phospholipase C (PLC) enzymes as central virulence factors during colonisation and infection. These PLCs hydrolyse host membrane phospholipids to generate diacylglycerol (DAG) and inositol triphosphate (IP3), thereby disrupting membrane integrity, perturbing intracellular signalling and promoting cytotoxicity. Hemolytic PLC isoforms, notably PlcH, contribute to erythrocyte lysis and nutrient acquisition, while non-hemolytic counterparts modulate immune responses and biofilm architecture. Secretion of PLCs involves dedicated export pathways, including the Twin Arginine Translocation (Tat) system and the type II secretion machinery, which together determine the exoproteome profile under environmental cues such as nutrient limitation. Interactions with complementary lipid-degrading enzymes—most prominently neutral ceramidase—amplify membrane damage and inflammatory signalling. Regulation of PLC expression by host-derived sphingolipids, mediated via the AraC-family regulator SphR, exemplifies the tight coupling between host lipid sensing and bacterial virulence. Insights into these mechanisms underscore the global significance of PLCs in chronic lung infections, wound colonisation and immunocompromised settings, and point to new antivirulence strategies.
Research from Nature Portfolio
Recent studies have characterised the contribution of the Twin Arginine Translocation system to the P. aeruginosa exoproteome, revealing that disruption of tat genes alters the secretion of key virulence determinants, including PLC family members. Under phosphate-starvation conditions, novel tat-dependent exoproteins were identified alongside PlcH and related enzymes, indicating that Tat-mediated export shapes the arsenal of lipid-targeting toxins and influences gene expression networks linked to host interaction. Another pivotal advance elucidated how the transcriptional regulator SphR senses host sphingosine to induce neutral ceramidase expression. SphR binds free sphingoid bases and upregulates ceramidase mRNA, thereby potentiating PlcH-driven haemolysis. This sphingolipid-responsive pathway demonstrates a mechanistic link between host membrane lipids and the coordinated deployment of complementary virulence factors in P. aeruginosa.
Phospholipase C Mechanisms in Pseudomonas aeruginosa Pathogenesis publication trend
The graph below shows the total number of articles in phospholipase c mechanisms in pseudomonas aeruginosa pathogenesis across all publications each year (not limited to Nature Index journals).
Technical terms
Phospholipase C (PLC): Enzyme that hydrolyses membrane phospholipids to generate diacylglycerol and inositol triphosphate.
Diacylglycerol (DAG): Lipid second messenger produced by PLC activity, which activates protein kinase C.
Inositol triphosphate (IP3): Water-soluble second messenger that mobilises intracellular calcium stores.
Hemolysis: Lysis of red blood cells resulting in the release of haemoglobin.
Ceramidase: Enzyme that cleaves ceramide to generate sphingosine, modulating membrane dynamics and signalling.
Twin Arginine Translocation (Tat) system: Protein export pathway that transports fully folded proteins across the cytoplasmic membrane.
Exoproteome: The ensemble of proteins secreted into the extracellular milieu by a bacterium.
References
- Phospholipase C: underrated players in microbial infections. Frontiers in Cellular and Infection Microbiology (2023).
- Contribution of the Twin Arginine Translocation system to the exoproteome of Pseudomonas aeruginosa. Scientific Reports (2016).
- Molecular mechanism for sphingosine-induced Pseudomonas ceramidase expression through the transcriptional regulator SphR. Scientific Reports (2016).
- Ceramidase Enhances Phospholipase C-induced Hemolysis by Pseudomonas aeruginosa *. Journal of Biological Chemistry (2007).
- Targeting the Pseudomonas aeruginosa Virulence Factor Phospholipase C With Engineered Liposomes. Frontiers in Microbiology (2022).
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