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Synthetic peptides that form nanostructured micelles have potent antibiotic and antibiofilm activity against polymicrobial infections.
Chou, Shuli; Guo, Huating; Zingl, Franz G; Zhang, Shiqing; Toska, Jonida; Xu, Bocheng; Chen, Yili; Chen, Peisong; Waldor, Matthew K; Zhao, Wenjing; Mekalanos, John J; Mou, Xiangyu.
Afiliação
  • Chou S; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, Guangdong 518107, China.
  • Guo H; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, Guangdong 518107, China.
  • Zingl FG; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115.
  • Zhang S; Department of Microbiology, Harvard Medical School, Boston, MA 02115.
  • Toska J; Howard Hughes Medical Institute, Boston, MA 02115.
  • Xu B; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, Guangdong 518107, China.
  • Chen Y; Department of Microbiology, Harvard Medical School, Boston, MA 02115.
  • Chen P; College of Animal Science, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Waldor MK; Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
  • Zhao W; Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
  • Mekalanos JJ; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115.
  • Mou X; Department of Microbiology, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A ; 120(4): e2219679120, 2023 01 24.
Article em En | MEDLINE | ID: mdl-36649429
The emergence of multidrug-resistant bacterial pathogens is a growing threat to global public health. Here, we report the development and characterization of a panel of nine-amino acid residue synthetic peptides that display potent antibacterial activity and the ability to disrupt preestablished microbial biofilms. The lead peptide (Peptide K6) showed bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus in culture and in monocultures and mixed biofilms in vitro. Biophysical analysis revealed that Peptide K6 self-assembled into nanostructured micelles that correlated with its strong antibiofilm activity. When surface displayed on the outer membrane protein LamB, two copies of the Peptide K6 were highly bactericidal to Escherichia coli. Peptide K6 rapidly increased the permeability of bacterial cells, and resistance to this toxic peptide occurred less quickly than that to the potent antibiotic gentamicin. Furthermore, we found that Peptide K6 was safe and effective in clearing mixed P. aeruginosa-S. aureus biofilms in a mouse model of persistent infection. Taken together, the properties of Peptide K6 suggest that it is a promising antibiotic candidate and that design of additional short peptides that form micelles represents a worthwhile approach for the development of antimicrobial agents.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Coinfecção / Antibacterianos Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Coinfecção / Antibacterianos Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article