Synthetic antibiofilm peptides

Fuente-Núñez, César de la; Cardoso, Marlon Henrique; Cândido, Elizabete de Souza; Franco, Octávio L.; Hancock, Robert E. W.

doi:10.1016/j.bbamem.2015.12.015

Cited by 183 publications

(148 citation statements)

References 69 publications

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“…As we have previously described, only 9 of the 20 natural amino acids (V, R, L, I, A, W, F, K, Q) are included in the new designs 4 charged residues (most commonly R), 7 or 8 hydrophobic residues, and no more than 1 glutamine (Q). D-amino acids are not naturally present in human peptides and therefore make them resistant to degradation by host proteases [30]. This is especially important in the oral cavity where most organisms produce secreted proteases [31].…”

Section: Discussionmentioning

confidence: 99%

“…Both the D-amino acid peptide DJK-5 and the L-amino acid peptide 1018 promote ppGpp degradation; in addition, the D-amino acid peptides have enhanced biological activities in vitro [23,24]. DJK-5 was one of several recently designed peptides [30] which showed enhanced, broad-spectrum anti-biofilm activity when tested on several species of Gram-negative pathogens [24,26]. According to de la Fuente-Núñez [24], D-enantiomeric peptides are designed not to be recognized by bacterial or host proteases that abound during infections.…”

Section: Discussionmentioning

confidence: 99%

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Treatment of Oral Biofilms by a D-Enantiomeric Peptide

et al. 2016

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Almost all dental diseases are caused by biofilms that consist of multispecies communities. DJK-5, which is a short D-enantiomeric, protease-resistant peptide with broad-spectrum anti-biofilm activity, was tested for its effect on oral multispecies biofilms. Peptide DJK-5 at 10 μg/mL effectively prevented the growth of these microbes in culture media in a time-dependent manner. In addition to the prevention of growth, peptide DJK-5 completely killed both Streptococcus mutans and Enterococcus faecalis suspended from biofilms after 30 minutes of incubation in liquid culture media. DJK-5 also led to the effective killing of microbes in plaque biofilm. The proportion of bacterial cells killed by 10 μg/mL of DJK-5 was similar after 1 and 3 days, both exceeding 85%. DJK-5 was able to significantly prevent biofilm formation over 3 days (P = 0.000). After 72 hours of exposure, DJK-5 significantly reduced and almost completely prevented plaque biofilm production by more than 90% of biovolume compared to untreated controls (P = 0.000). The proportion of dead biofilm bacteria at the 10 μg/mL DJK-5 concentration was similar for 1- and 3-day-old biofilms, whereby >86% of the bacteria were killed. DJK-5 was also able to kill >79% and >85% of bacteria, respectively, after one-time and three brief treatments of 3-day-old biofilms. The combination of DJK-5 and chlorhexidine showed the best bacterial killing among all treatments, with ~83% and >88% of bacterial cells killed after 1 and 3 minutes, respectively. No significant difference was found in the percentage of biofilm killing amongst three donor plaque samples after DJK-5 treatment. In particular, DJK-5 showed strong performance in inhibiting biofilm development and eradicating pre-formed oral biofilms compared to L-enantiomeric peptide 1018. DJK-5 was very effective against oral biofilms when used alone or combined with chlorhexidine, and may be a promising agent for use in oral anti-biofilm strategies in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Treatment of Oral Biofilms by a D-Enantiomeric Peptide

et al. 2016

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“…As a result, only a minority of known AMPs, including GL13K (Hirt and Gorr 2013;Chen et al 2014), are also known to be active against bacterial biofilms (Di Luca et al 2015). Since biofilms are difficult to eradicate once they are established, recent strategies have focused on peptides that are specifically designed to prevent biofilm formation or eliminate existing biofilms (e.g., BAR and 1018; Daep et al 2010;de la Fuente-Núñez et al 2016). Some of these peptides specifically attack cellular mechanisms involved in biofilm formation (e.g., cell attachment) and thus may cause less bacterial resistance than bactericidal AMPs.…”

Section: Entrapment By Surface Proteins and Polysaccharidesmentioning

confidence: 99%

Antimicrobial Peptides: Mechanisms of Action and Resistance

2016

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More than 40 antimicrobial peptides and proteins (AMPs) are expressed in the oral cavity. These AMPs have been organized into 6 functional groups, 1 of which, cationic AMPs, has received extensive attention in recent years for their promise as potential antibiotics. The goal of this review is to describe recent advances in our understanding of the diverse mechanisms of action of cationic AMPs and the bacterial resistance against these peptides. The recently developed peptide GL13K is used as an example to illustrate many of the discussed concepts. Cationic AMPs typically exhibit an amphipathic conformation, which allows increased interaction with negatively charged bacterial membranes. Peptides undergo changes in conformation and aggregation state in the presence of membranes; conversely, lipid conformation and packing can adapt to the presence of peptides. As a consequence, a single peptide can act through several mechanisms depending on the peptide's structure, the peptide:lipid ratio, and the properties of the lipid membrane. Accumulating evidence shows that in addition to acting at the cell membrane, AMPs may act on the cell wall, inhibit protein folding or enzyme activity, or act intracellularly. Therefore, once a peptide has reached the cell wall, cell membrane, or its internal target, the difference in mechanism of action on gram-negative and gram-positive bacteria may be less pronounced than formerly assumed. While AMPs should not cause widespread resistance due to their preferential attack on the cell membrane, in cases where specific protein targets are involved, the possibility exists for genetic mutations and bacterial resistance. Indeed, the potential clinical use of AMPs has raised the concern that resistance to therapeutic AMPs could be associated with resistance to endogenous host-defense peptides. Current evidence suggests that this is a rare event that can be overcome by subtle structural modifications of an AMP.

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“…Due to general membrane disruption activity, eCAPs are often able to kill a broad range of microbial species and strains, even multidrug resistant and select agent pathogens[14, 18, 19]. Considering that infection biofilms are often polymicrobial, treatment with eCAPs is potentially beneficial for their broad-spectrum activity.…”

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confidence: 99%

“…While the ability of eCAPs to treat established biofilms is of major interest, their use in preventing biofilm biogenesis, either by prophylactic treatment or coating of medical implants[11, 18], is of equal importance. There is current interest in tethering eCAPs to implant materials, with some success in maintaining bactericidal activity[21].…”

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confidence: 99%