title: Preclinical investigations reveal the broad-spectrum neutralizing activity of peptide Pep19-2.5 on bacterial pathogenicity factors.
abstract: Bacterial infections are known to cause severe health-threatening conditions, including sepsis. All attempts to get this disease under control failed in the past, and especially in times of increasing antibiotic resistance, this leads to one of the most urgent medical challenges of our times. We designed a peptide to bind with high affinity to endotoxins, one of the most potent pathogenicity factors involved in triggering sepsis. The peptide Pep19-2.5 reveals high endotoxin neutralization efficiency in vitro, and here, we demonstrate its antiseptic/anti-inflammatory effects in vivo in the mouse models of endotoxemia, bacteremia, and cecal ligation and puncture, as well as in an ex vivo model of human tissue. Furthermore, we show that Pep19-2.5 can bind and neutralize not only endotoxins but also other bacterial pathogenicity factors, such as those from the Gram-positive bacterium Staphylococcus aureus. This broad neutralization efficiency and the additive action of the peptide with common antibiotics makes it an exceptionally appropriate drug candidate against bacterial sepsis and also offers multiple other medication opportunities.
authors: Division of Biophysics, Research Center Borstel, Borstel, Germany. lheinbockel@fz-borstel.de
authors: Lena
authors: L
authors: Heinbockel
authors: Susana
authors: S
authors: Sánchez-Gómez
authors: Guillermo
authors: G
authors: Martinez de Tejada
authors: Sabine
authors: S
authors: Dömming
authors: Julius
authors: J
authors: Brandenburg
authors: Yani
authors: Y
authors: Kaconis
authors: Mathias
authors: M
authors: Hornef
authors: Aline
authors: A
authors: Dupont
authors: Sebastian
authors: S
authors: Marwitz
authors: Torsten
authors: T
authors: Goldmann
authors: Martin
authors: M
authors: Ernst
authors: Thomas
authors: T
authors: Gutsmann
authors: Tobias
authors: T
authors: Schürholz
authors: Klaus
authors: K
authors: Brandenburg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology / Q000401:mortality; D004195:Disease Models, Animal; D004357:Drug Synergism; D019446:Endotoxemia / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology / Q000401:mortality; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology / Q000401:mortality; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology / Q000401:mortality; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity*; D016019:Survival Analysis; D037521:Virulence Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; C000621961:Pep19-2.5 peptide; D010455:Peptides; D037521:Virulence Factors