Anti-Staphylococcal Biofilm Effects of Human Cathelicidin Peptides

Abstract

Staphylococcus aureus can live together in the form of biofilms to avoid elimination by the host. Thus, a useful strategy to counteract bacterial biofilms is to re-engineer human antimicrobial peptide LL-37 so that it can be used as a remedy for preventing and removing biofilms. This study reports antibiofilm effects of four human cathelicidin LL-37 peptides against community-associated and hospital isolated methicillin-resistant Staphylococcus aureus (MRSA) strains. Although the intact molecule LL-37 inhibited biofilm formation at low concentrations, it did not inhibit bacterial attachment nor disrupt preformed biofilms. However, two 17-residue peptides, GF-17 and 17BIPHE2, inhibited bacterial attachment, biofilm growth, and disrupted established biofilms. An inactive peptide RI-10 was used as a negative control. Our results obtained using the S. aureus mutants in a static biofilm model are consistent with the literature obtained in a flow cell biofilm model. Because 17BIPHE2 is the most effective biofilm disruptor with desired stability to proteases, it is a promising lead for developing new anti-MRSA biofilm agents.

Providencia stuartii form biofilms and floating communities of cells that display high resistance to environmental insults

“…stuartii growth (Fig 1A). Data show that Omp-Pst2 is involved in pH regulation (Fig 4G) and could be in charge of ammonium clearance/neutralization from/in the periplasm, a hypothesis supported by electrophysiology data [40] and more recently molecular dynamics simulations on the porin [42]. Our data add to the growing body of evidence that suggests an implication of OM components in biofilm formation and regulation [48,49].…”

“…Indeed, MD simulations have suggested that Omp-Pst2 could be involved in the facilitated transport of cations from the periplasm to the extracellular side of the OM [42]. They furthermore highlighted that Omp-Pst2 channel would respond by gating to a massive transit of cations from the external medium to the periplasm [42]. Thus, we favour the hypothesis that Omp-Pst2 alleviates the toxic effects of urea on P .…”

“…(iii) Omp-Pst2 could be involved in the direct efflux of periplasmic ammonium and in limiting its repenetration into the periplasm; this is the only hypothesis that fits the prior knowledge on Omp-Pst2. Indeed, MD simulations have suggested that Omp-Pst2 could be involved in the facilitated transport of cations from the periplasm to the extracellular side of the OM [42]. They furthermore highlighted that Omp-Pst2 channel would respond by gating to a massive transit of cations from the external medium to the periplasm [42].…”

“…MD simulations suggested that Omp-Pst2 atypical voltage-gating behaviour is asymmetric and triggered by the influx of cations from the extracellular to the periplasmic side of the porin. Efflux of cations, on the other hand, would be facilitated, suggesting a potential role for this porin in the regulation of charge distribution across the OM [42]. …”

Host defense antimicrobial peptides as antibiotics: design and application strategies

“…For instance, merecidin (formerly known as 17BIPHE2), a human LL-37 derived peptide, can disrupt the biofilms of S. aureus USA300 under laboratory conditions [65], but is unable to do so in the case of P. aeruginosa . This may result from the complex nature of biofilms with a protective biopolymer coating for the bacterial communities.…”