Researchers Identify Bactericidal Phospholipase Enzyme from Archaea
Researchers have identified a protein called cinquedea, secreted by the halophilic archaeon Haloferax larsenii, that kills halophilic Pontibacillus bacteria at nanomolar concentrations by acting as a phospholipase that degrades their cell membranes. The enzyme shares structural similarities with a phospholipase A1 found in hornet venom, and its bactericidal mechanism — membrane disruption — is distinct from previously discovered archaeal antibacterial strategies involving peptidoglycan hydrolases. This finding reinforces the idea that archaea represent an underexplored reservoir of novel antibacterial compounds, with potential implications for antibiotic discovery.
A new study published on bioRxiv describes cinquedea, a β-hydrolase enzyme secreted by the salt-loving archaeon Haloferax larsenii s5a-1 that kills halophilic Pontibacillus bacteria at nanomolar concentrations. The enzyme functions as a phospholipase, cleaving phosphatidylglycerol — the primary lipid component of the Pontibacillus membrane — and producing lysophosphatidylglycerol as a cleavage product, consistent with phospholipase A activity. Bacteria exposed to cinquedea exhibit severe morphological abnormalities indicative of extensive cell envelope damage. Structurally, cinquedea resembles a phospholipase A1 isolated from hornet venom, suggesting an intriguing evolutionary parallel between archaeal and animal-derived antimicrobial enzymes. This discovery follows recent findings that some archaea produce bactericidal peptidoglycan hydrolases, indicating that archaeal antibacterial strategies are mechanistically diverse. The authors argue their work provides a framework for systematically identifying and characterizing other bactericidal proteins of archaeal origin, positioning archaea as a significant and largely untapped source of new antibacterial compounds.
What's missing
As a preprint, this study has not yet undergone formal peer review, so findings should be treated as preliminary. The study does not address whether cinquedea or related archaeal phospholipases show activity against clinically relevant pathogens, nor whether the enzyme is toxic to eukaryotic cells — a critical consideration for any therapeutic application. The ecological conditions under which Haloferax larsenii and Pontibacillus co-occur and compete in nature are not fully characterized, leaving the in vivo relevance of this interaction uncertain.
What different sources said
- bioRxivCenter
A Bactericidal Phospholipase from Archaea
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