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Updated: Jul 19, 2026

A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
The potent anti-Staphylococcus aureus activity of a sterile rabbit inflammatory fluid is due to a 14-kD phospholipase
Y Weinrauch1, P Elsbach, L M Madsen
1Department of Microbiology, New York University School of Medicine, New York 10016, USA.
Abstract:
The cell-free fluid (ascitic fluid, AF) of a sterile inflammatory peritoneal exudate elicited in rabbits is potently bactericidal for complement-resistant gram-negative as well as gram-positive bacterial species. This activity is absent in plasma. We now show that essentially all activity in AF against Staphylococcus aureus is attributable to a group II 14-kD phospholipase A2 (PLA2), previously purified from AF in this laboratory. Antistaphylococcal activity of purified PLA2 and of whole AF containing a corresponding amount of PLA2 was comparable and blocked by anti-AF-PLA2 serum. At concentrations present in AF (approximately 10 nM), AF PLA2 kills > 2 logs of 10(6) S. aureus/ml, including methicillin-resistant clinical isolates, and other species of gram-positive bacteria. Human group II PLA2 displays similar bactericidal activity toward S. aureus (LD90 approximately 1-5 nM), whereas 14-kD PLA2 from pig pancreas and snake venom are inactive even at micromolar doses. Bacterial killing by PLA2 requires Ca2+ and catalytic activity and is accompanied by bacterial phospholipolysis and disruption of the bacterial cell membrane and cell wall. These findings reveal that group II extracellular PLA2, the function of which at inflammatory sites has been unclear, is an extraordinarily potent endogenous antibiotic against S. aureus and other gram-positive bacteria.
Insights
Group II phospholipase A2 (PLA2) in ascitic fluid acts as a potent endogenous antibiotic. This enzyme effectively kills Staphylococcus aureus and other gram-positive bacteria by disrupting their cell membranes.
Area of Science:
- Biochemistry
- Microbiology
- Immunology
Background:
- Ascitic fluid (AF) from sterile peritoneal exudates exhibits potent bactericidal activity against various bacteria.
- This activity is notably absent in plasma, suggesting a specific component within AF is responsible.
- Previous research identified a group II 14-kD phospholipase A2 (PLA2) in AF.
Purpose of the Study:
- To determine if the group II 14-kD PLA2 in AF is responsible for its bactericidal activity against Staphylococcus aureus.
- To characterize the mechanism and potency of AF PLA2 as an antibacterial agent.
Main Methods:
- Purification and characterization of group II 14-kD PLA2 from rabbit AF.
- Assaying the bactericidal activity of purified PLA2 and whole AF against Staphylococcus aureus.
- Investigating the role of calcium ions (Ca2+) and catalytic activity in PLA2-mediated bacterial killing.
- Analyzing bacterial cell membrane and cell wall integrity post-treatment.
Main Results:
- Essentially all antistaphylococcal activity in AF is attributable to group II 14-kD PLA2.
- Purified PLA2 and whole AF showed comparable bactericidal activity against Staphylococcus aureus, including methicillin-resistant strains.
- Human group II PLA2 demonstrated potent activity, while PLA2 from other sources (pig pancreas, snake venom) was inactive.
- Bacterial killing by PLA2 requires Ca2+ and catalytic activity, leading to cell membrane and wall disruption.
Conclusions:
- Group II extracellular PLA2 is a potent endogenous antibiotic against Staphylococcus aureus and other gram-positive bacteria.
- The findings clarify the functional role of group II PLA2 at inflammatory sites.
- PLA2 represents a novel therapeutic target for combating Gram-positive bacterial infections.
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