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Two distinct amphipathic peptide antibiotics with systemic efficacy.
Lakshmaiah Narayana, Jayaram; Mishra, Biswajit; Lushnikova, Tamara; Wu, Qianhui; Chhonker, Yashpal S; Zhang, Yingxia; Zarena, D; Salnikov, Evgeniy S; Dang, Xiangli; Wang, Fangyu; Murphy, Caitlin; Foster, Kirk W; Gorantla, Santhi; Bechinger, Burkhard; Murry, Daryl J; Wang, Guangshun.
Afiliação
  • Lakshmaiah Narayana J; Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5900.
  • Mishra B; Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5900.
  • Lushnikova T; Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5900.
  • Wu Q; Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5900.
  • Chhonker YS; Clinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198.
  • Zhang Y; Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5900.
  • Zarena D; Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5900.
  • Salnikov ES; Chemistry Institute UMR7177, University of Strasbourg/CNRS, F-67008 Strasbourg, France.
  • Dang X; Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5900.
  • Wang F; Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5900.
  • Murphy C; Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5900.
  • Foster KW; Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5900.
  • Gorantla S; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198.
  • Bechinger B; Chemistry Institute UMR7177, University of Strasbourg/CNRS, F-67008 Strasbourg, France.
  • Murry DJ; Institut Universitaire de France, 75231 Paris Cedex 05, France.
  • Wang G; Clinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198.
Proc Natl Acad Sci U S A ; 117(32): 19446-19454, 2020 08 11.
Article em En | MEDLINE | ID: mdl-32723829
Antimicrobial peptides are important candidates for developing new classes of antibiotics because of their potency against antibiotic-resistant pathogens. Current research focuses on topical applications and it is unclear how to design peptides with systemic efficacy. To address this problem, we designed two potent peptides by combining database-guided discovery with structure-based design. When bound to membranes, these two short peptides with an identical amino acid composition can adopt two distinct amphipathic structures: A classic horizontal helix (horine) and a novel vertical spiral structure (verine). Their horizontal and vertical orientations on membranes were determined by solid-state 15N NMR data. While horine was potent primarily against gram-positive pathogens, verine showed broad-spectrum antimicrobial activity. Both peptides protected greater than 80% mice from infection-caused deaths. Moreover, horine and verine also displayed significant systemic efficacy in different murine models comparable to conventional antibiotics. In addition, they could eliminate resistant pathogens and preformed biofilms. Significantly, the peptides showed no nephrotoxicity to mice after intraperitoneal or intravenous administration for 1 wk. Our study underscores the significance of horine and verine in fighting drug-resistant pathogens.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos Catiônicos Antimicrobianos / Antibacterianos Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos Catiônicos Antimicrobianos / Antibacterianos Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article