title: The lysine-peptoid hybrid LP5 maintain activity under physiological conditions and affects virulence gene expression in Staphylococcus aureus.
abstract: The antimicrobial peptide, LP5, is a lysine-peptoid hybrid, with antimicrobial activity against clinically relevant bacteria. Here, we investigated how various environmental conditions affect the antimicrobial activity of LP5 against Staphylococcus aureus (S. aureus). We found that LP5 maintained activity under host physiological conditions of NaCl, MgCl2 and pH. However, when exposed to serum, LP5 lost activity. Furthermore, when increasing NaCl concentration and lowering pH, the peptide showed reduces activity. When investigating the tolerance mechanisms of S. aureus toward antimicrobial peptides, we found that LP5 was protease resistant. However, the dltA and vraF genes, involved in reducing the net anionic charge of the bacterial cell envelope and sensing of antimicrobial peptides, respectively, played a role in the tolerance of S. aureus against LP5. In addition, the exposure of S. aureus to sub-inhibitory concentrations of LP5 affected the expression of the major virulence factors of S. aureus, revealing a potential as anti-virulence compound. Thus, these results show how environmental factors affect the peptide efficiency and further add to the knowledge on how the peptide affects S. aureus, which is crucial information for designing new peptides for optimizing antimicrobial therapy.
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Frederiksberg, Denmark. Electronic address: sannegottschalk@gmail.com.
authors: Sanne
authors: S
authors: Gottschalk
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Frederiksberg, Denmark. Electronic address: hi@sund.ku.dk.
authors: Hanne
authors: H
authors: Ingmer
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Frederiksberg, Denmark. Electronic address: leth@sund.ku.dk.
authors: Line E
authors: LE
authors: Thomsen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019729:Carbon-Oxygen Ligases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002645:Chickens; D019286:Endopeptidase K / Q000737:chemistry; D015870:Gene Expression; D006863:Hydrogen-Ion Concentration; D015636:Magnesium Chloride / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D055550:Protein Stability; D044967:Serum / Q000737:chemistry; D012965:Sodium Chloride / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D014357:Trypsin / Q000737:chemistry; D014774:Virulence; D037521:Virulence Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D037521:Virulence Factors; D015636:Magnesium Chloride; D012965:Sodium Chloride; D014357:Trypsin; D019286:Endopeptidase K; D019729:Carbon-Oxygen Ligases
keywords: Anti-virulence factor; Antimicrobial peptide; LP5 activity; LP5 stability; Lysine-peptoid hybrid; S. aureus