Quantitative imaging of the action of vCPP2319, an antimicrobial peptide from a viral scaffold, against Staphylococcus aureus biofilms of a clinical isolate

Dias, Susana A.; Pinto, Sandra N.; Silva-Herdade, Ana S.; Cavaco, Marco; Neves, Vera; Tavares, Luís; Oliveira, Manuela; Andreu Martínez, David; Coutinho, Ana; Castanho, Miguel A.R.B.; Salomé Veiga, Ana

doi:http://dx.doi.org/10.1021/acsinfecdis.3c00195

Quantitative imaging of the action of vCPP2319, an antimicrobial peptide from a viral scaffold, against Staphylococcus aureus biofilms of a clinical isolate

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Citació

Dias SA, Pinto SN, Silva-Herdade AS, Cavaco M, Neves V, Tavares L, Oliveira M, Andreu D, Coutinho A, Castanho MARB, Veiga AS. Quantitative imaging of the action of vCPP2319, an antimicrobial peptide from a viral scaffold, against Staphylococcus aureus biofilms of a clinical isolate. ACS Infect Dis. 2023 Oct 13;9(10):1889-900. DOI: 10.1021/acsinfecdis.3c00195

Resum

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.