Quantitative Imaging of the Action of vCPP2319, an Antimicrobial Peptide from a Viral Scaffold, against Staphylococcus aureus Biofilms of a Clinical Isolate.
Susana A DiasSandra Nunes PintoAna S Silva-HerdadeMarco CavacoVera NevesLuís TavaresManuela OliveiraDavid AndreuAna CoutinhoMiguel A R B CastanhoAna Salomé VeigaPublished in: ACS infectious diseases (2023)
The formation of biofilms is a common virulence factor that makes bacterial infections difficult to treat and a major human health problem. Biofilms are bacterial communities embedded in a self-produced matrix of extracellular polymeric substances (EPS). In this work, we show that vCPP2319, a polycationic peptide derived from the capsid protein of Torque teno douroucouli virus, is active against preformed Staphylococcus aureus biofilms produced by both a reference strain and a clinical strain isolated from a diabetic foot infection, mainly by the killing of biofilm-embedded bacteria. The direct effect of vCPP2319 on bacterial cells was imaged using atomic force and confocal laser scanning microscopy, showing that the peptide induces morphological changes in bacterial cells and membrane disruption. Importantly, vCPP2319 exhibits low toxicity toward human cells and high stability in human serum. Since vCPP2319 has a limited effect on the biofilm EPS matrix itself, we explored a combined effect with α-amylase (EC 3.2.1.1), an EPS matrix-degrading enzyme. In fact, α-amylase decreases the density of S. aureus biofilms by 2.5-fold. Nonetheless, quantitative analysis of bioimaging data shows that vCPP2319 partially restores biofilm compactness after digestion of the polysaccharides, probably due to electrostatic cross-bridging of the matrix nucleic acids, which explains why α-amylase fails to improve the antibacterial action of the peptide.
Keyphrases
- staphylococcus aureus
- candida albicans
- biofilm formation
- high resolution
- induced apoptosis
- human health
- pseudomonas aeruginosa
- cell cycle arrest
- risk assessment
- methicillin resistant staphylococcus aureus
- oxidative stress
- single molecule
- drug delivery
- escherichia coli
- sars cov
- climate change
- cell death
- optical coherence tomography
- signaling pathway
- electronic health record
- fluorescent probe
- photodynamic therapy
- artificial intelligence
- cell proliferation
- living cells