Amphibian antimicrobial peptide fallaxin analogue FL9 affects virulence gene expression and DNA replication in Staphylococcus aureus

Abstract

The rapid rise in antibiotic-resistant pathogens is causing increased health concerns, and consequently there is an urgent need for novel antimicrobial agents. Antimicrobial peptides (AMPs), which have been isolated from a wide range of organisms, represent a very promising class of novel antimicrobials. In the present study, the analogue FL9, based on the amphibian AMP fallaxin, was studied to elucidate its mode of action and antibacterial activity against the human pathogen Staphylococcus aureus. Our data showed that FL9 may have a dual mode of action against S. aureus. At concentrations around the MIC, FL9 bound DNA, inhibited DNA synthesis and induced the SOS DNA damage response, whereas at concentrations above the MIC the interaction between S. aureus and FL9 led to membrane disruption. The antibacterial activity of the peptide was maintained over a wide range of NaCl and MgCl 2 concentrations and at alkaline pH, while it was compromised by acidic pH and exposure to serum. Furthermore, at subinhibitory concentrations of FL9, S. aureus responded by increasing the expression of two major virulence factor genes, namely the regulatory rnaIII and hla, encoding a-haemolysin. In addition, the S. aureus-encoded natural tolerance mechanisms included peptide cleavage and the addition of positive charge to the cell surface, both of which minimized the antimicrobial activity of FL9. Our results add new information about FL9 and its effect on S. aureus, which may aid in the future development of analogues with improved therapeutic potential.

An Enhanced Variant Designed From DLP4 Cationic Peptide Against Staphylococcus aureus CVCC 546

“…Then, AMPs can destroy the cell envelope and effectively induce a leakage of cytosol (Huang et al, 2010). It has been proven in our study that ID13 had the ability to destroy the cell envelope and cause K + or other contents to release extracellularly (Figures 4, 6), and then bound to intracellular target gDNA and destroyed its helical structure (Figure 5), which might result in the inhibition of DNA synthesis (Gottschalk et al, 2015). In contrast, DLP4 showed less potent damage to cell membrane than that of ID13 (Figures 4, 6), but it showed stronger binding ability to S. aureus gDNA (Figure 5), which might attribute to its less α-helix content in bacterial membrane mimicking conditions and more net positive charges.…”

“…Antibiotics play pivotal roles in disease prevention, growth promotion, and production improvement in animal husbandry (Ferber, 2002;Cheng et al, 2014;Van Boeckel et al, 2015). Nevertheless, the long-term use of antibiotics in animal breeding can accelerate the emergence of antibiotic-resistant bacteria (ARB), including Staphylococcus aureus, which can cause trauma infection, abscess, cellulitis, mastitis, endometritis, arthritis, septicemia, and sepsis in animals (Fluit, 2012;Foster, 2012;Dan et al, 2019). It has been found that S. aureus is resistant to tetracycline, methicillin, erythromycin, clindamycin, ciprofloxacin, and vancomycin (Hiramatsu, 2001;Lai et al, 2018;Pirolo et al, 2019).…”

Effects of the antimicrobial peptide L12 against multidrug‑resistant Staphylococcus aureus

“…However, the molecular mechanism underlying Enterococcus resistance to L12 requires further investigation in future studies. The MIC of L12 against S. aureus was similar to traditional antibacterial drugs, and the antibacterial activity of L12 was comparable with other AMPs (22)(23)(24)(25). Furthermore, the MICs of L12 exhibited no correlation with resistance to the tested antibiotics, the strains resistant to more antibiotics were not more resistant to L12, which suggested that L12 may be used to treat infections caused by MRSA strains.…”

Antimicrobial activity of the indolicidin‐derived novel synthetic peptide In‐58

“…It was also shown that peptides taken at subinhibitory concentrations induce an SOS response of bacterial cells. Finally, we demonstrated the killing effect of indolicidin, and its analogue was realized because of the disturbance of the bacterial cell wall, while the interaction with intracellular DNA may lead to other effects; for example, to affecting of expression of some genes .…”