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Quantifying the Cytotoxicity of Staphylococcus aureus Against Human Polymorphonuclear Leukocytes
Published on: January 3, 2020
Effect of primycin on growth-arrested cultures and cell integrity of Staphylococcus aureus
Péter Feiszt1,2, György Schneider2, Levente Emődy2,3
11 PannonPharma Ltd. , Pécsvárad, Hungary.
Abstract:
Bactericidal effect against non-dividing bacteria is a very advantageous, but rare characteristic among antimicrobial agents, mostly possessed by those affecting the cell membrane. These kinds of agents can kill bacterial cells without lysis. We assessed these characteristics on primycin, a topical anti-staphylococcal agent highly effective against prevalent multiresistant strains, as it also acts on the cell membrane. In time-kill studies, primycin preserved its bactericidal activity against growth-arrested Staphylococcus aureus cultures. The bactericidal action was slower against growth-arrested cultures compared to the exponentially growing ones to different extents depending on the manner of arrest. The bactericidal effect was less influenced by stringent response and by protein synthesis inhibition, proving that it does not depend on metabolic activity. In contrast, uncoupling of the membrane potential predominantly slowed, and low temperature almost stopped killing of bacteria. In consideration of published data, these facts suggest that the antibacterial action of primycin involves disrupting of the membrane potential, and is predominantly influenced by the membrane fluidity. Optical density measurements and transmission electron microscopy verified that primycin kills bacterial cells without lysis. These results reveal favorable characteristics of primycin and point to, and broaden the knowledge on its membrane-targeted effect.
Insights
Primycin effectively kills non-dividing Staphylococcus aureus without causing cell lysis, demonstrating a rare bactericidal characteristic. Its action targets the cell membrane, offering potential against resistant bacterial strains.
Area of Science:
- Microbiology
- Pharmacology
Background:
- Bactericidal agents that kill non-dividing bacteria without lysis are rare and advantageous.
- Primycin is a topical anti-staphylococcal agent with known efficacy against multiresistant strains, acting on the cell membrane.
Purpose of the Study:
- To assess the bactericidal characteristics of primycin against non-dividing Staphylococcus aureus.
- To elucidate the mechanism of primycin's action on bacterial cell membranes.
Main Methods:
- Time-kill studies were performed on growth-arrested Staphylococcus aureus cultures.
- Bacterial response to primycin was evaluated under conditions affecting metabolic activity, membrane potential, and temperature.
- Optical density measurements and transmission electron microscopy were used to assess cell integrity.
Main Results:
- Primycin maintained bactericidal activity against growth-arrested Staphylococcus aureus, though at a slower rate than against exponentially growing cells.
- The bactericidal effect was independent of metabolic activity (stringent response, protein synthesis inhibition).
- Disruption of membrane potential and membrane fluidity significantly influenced primycin's killing efficacy, while cell lysis was not observed.
Conclusions:
- Primycin exhibits a favorable bactericidal effect against non-dividing bacteria without causing lysis.
- The mechanism of action involves disruption of the bacterial cell membrane potential and is influenced by membrane fluidity.
- Primycin's membrane-targeting action warrants further investigation for treating infections caused by resistant bacteria.

