Violacein Targets the Cytoplasmic Membrane of Bacteria

Autor(es)

Cauz, Ana C. G. ^[1] ; Carretero, Gustavo P. B. ^[2] ; Saraiva, Greice K. V. ^[2] ; Park, Peter ^[2] ; Mortara, Laura ^[2] ; Cuccovia, Iolanda M. ^[2] ; Brocchi, Marcelo ^[1] ; Gueiros-Filho, Frederico J. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Biol, Dept Genet Evolucao Microbiol & Imunol, Rua Monteiro Lobato 255, BR-13083862 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Quim, Dept Bioquim, Ave Prof Lineu Prestes 748, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ACS INFECTIOUS DISEASES; v. 5, n. 4, p. 539-549, APR 2019.
• Citações Web of Science: 0

Resumo

Violacein is a tryptophan-derived purple pigment produced by environmental bacteria, which displays multiple biological activities, including strong inhibition of Gram-positive pathogens, Here, we applied a combination of experimental approaches to identify the mechanism by which violacein kills Gram-positive bacteria. Fluorescence microscopy showed that violacein quickly and dramatically permeabilizes B. subtilis and S. aureus cells. Cell permeabilization was accompanied by the appearance of visible discontinuities or rips in the cytoplasmic membrane, but it did not affect the cell wall. Using in vitro experiments, we showed that violacein binds directly to liposomes made with commercial and bacterial phospholipids and perturbs their structure and permeability. Furthermore, molecular dynamics simulations were employed to reveal how violacein inserts itself into lipid bilayers. Thus, our combined results demonstrate that the cytoplasmic membrane is the primary target of violacein in bacteria. The implications of this finding for the development of violacein as a therapeutic agent are discussed. (AU)

• Processo FAPESP: 13/08166-5 - Química em interfaces: interações de fármacos, peptídios e enzimas com membranas modelos
• Beneficiário: Iolanda Midea Cuccovia
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/05203-5 - Como bactérias coordenam a biogênese de membranas com o crescimento e a divisão celular?
• Beneficiário: Frederico José Gueiros Filho
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/20116-0 - Análise dos mecanismos de atividade antibacteriana da violaceína sobre Staphylococcus aureus e parâmetros farmacocinéticos
• Beneficiário: Marcelo Brocchi
• Linha de fomento: Auxílio à Pesquisa - Regular