The Importance of Cyclic Structure for Labaditin on Its Antimicrobial Activity Against Staphylococcus aureus

Barbosa, Simone C.Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil (author)

Antimicrobial resistance has reached alarming levels in many countries, thus leading to a search for new classes of antibiotics, such as antimicrobial peptides whose activity is exerted by interacting specifically with the microorganism membrane. In this study, we investigate the molecular-level mechanism of action for Labaditin (Lo), a 10-amino acid residue cyclic peptide from Jatropha multifida with known bactericidal activity againstStreptococcus mutans. We show that Lo is also effective against Staphylococcus aureus(S. aureus) but this does not apply to its linear analogue (L1). Using polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), we observed with that the secondary structure of Lo was preserved upon interacting with Langmuir monolayers from a phospholipid mixture mimicking S. aureus membrane, in contrast to L1. This structure preservation for the rigid, cyclic Lo is key for the self-assembly of peptide nanotubes that induce pore formation in large unilamellar vesicles (LUVs), according to permeability assays and dynamic light scattering measurements. In summary, the comparison between Labaditin (Lo) and its linear analogue L1 allowed us to infer that the bactericidal activity of Lo is more related to its interaction with the membrane. It does not require specific metabolic targets, which makes cyclic peptides promising for antibiotics without bacteria resistance.

Nobre, Thatyane M.Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil (author)
Volpati, DiogoMittuniversitetet,Avdelningen för naturvetenskap(Swepub:miun)diovol (author)
Ciancaglini, PietroDepartamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil (author)
Cilli, Eduardo M.Instituto de Química, Universidade Estadual Paulista, Araraquara, SP, Brazil (author)
Lorenzon, Esteban N.Departamento de Bioquímica e Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Brazil (author)
Oliveira Jr., Osvaldo N.Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil (author)
Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP, BrazilAvdelningen för naturvetenskap (creator_code:org_t)

By the author/editor: Barbosa, Simone ...; Nobre, Thatyane ...; Volpati, Diogo; Ciancaglini, Pie ...; Cilli, Eduardo M ...; Lorenzon, Esteba ...; show more...; Oliveira Jr., Os ...; show less...

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