Peptides as a strategy against biofilm-forming microorganisms: Structure-activity relationship perspectives

Borowski, Rafael Gomes Von; Macêdo, Alexandre José; Gnoatto, Simone Cristina Baggio

doi:10.1016/j.ejps.2017.11.008

Cited by 21 publications

(14 citation statements)

References 101 publications

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“…Peptides are fundamental molecules made up of 2–50 amino acids, with many biological functions. Indeed, their versatile chemical features such as malleability and multifunctionality, make them good models for the synthesis of new bioactive compounds (Von Borowski et al, 2017 ). Antimicrobial peptides (AMPs) are very interesting molecules to be explored in the search for antibiofilm agents to replace conventional antibiotics.…”

Section: Introductionmentioning

confidence: 99%

Promising Antibiofilm Activity of Peptidomimetics

et al. 2018

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Pathogenic biofilms are a global health care concern, as they can cause extensive antibiotic resistance, morbidity, mortality, and thereby substantial economic loss. Scientific efforts have been made over the past few decades, but so far there is no effective treatment targeting the bacteria in biofilms. Antimicrobial peptidomimetics have been proposed as promising potential anti-biofilm agents. Indeed, these structurally enhanced molecules can mimic the action of peptides but are not susceptible to proteolysis or immunogenicity, the characteristic limitations of natural peptides. Here, we provide insights into antibiofilm peptidomimetic strategies and molecular targets, and discuss the design of two major peptidomimetics classes: AApeptides (N-acylated-N-aminoethyl-substituted peptides) and peptoids (N-substituted glycine units). In particular, we present details of their structural diversity and discuss the possible improvements that can be implemented in order to develop antibiofilm drug alternatives.

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Section: Introductionmentioning

confidence: 99%

Promising Antibiofilm Activity of Peptidomimetics

et al. 2018

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“…If pseudonajide mainly acts on teichoic and lipoteichoic acids, the reduction in adhesion could be one of the causes of both biofilm reduction and outright eradication. It is also important to emphasize the characteristics of cationic antibiofilm peptides, described by Von Borowski et al (51). They showed that lysine (K) and phenylalanine (F) are the most frequently found amino acids in antibiofilm peptides, and this is clearly also the case for pseudonajide (KRFKKFFMKLK).…”

Section: Discussionmentioning

confidence: 95%

Pseudonajide is an antibiotic peptide derived from snake venom that alter cell wall and membrane integrity interfering on biofilm formation.

Schneider

Primon-Barros

Borowski

et al. 2019

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Background The increase of bacterial resistance phenotype cases is a global health problem. New strategies in scientific community must be explored in order to create new treatment alternatives. Animal venoms are a good source for antimicrobial peptides (AMPs), which are excellent candidates for new antimicrobial drug development. These molecules have highly diverse targets in prokaryotic cells, making resistance phenotype development more difficult. Results In this study we present a peptide of just 11 amino acids which has antimicrobial and antibiofilm activity against Staphyloccocus epidermidis. Named pseudonajide, it is derived from Pseudonaja textilis venom. Pseudonajide was selected based on the sequence alignments of various snake venom peptides that displayed activity against bacteria. Several concentrations of pseudonajide were tested in antibiofilm activity essay, it was detected that 25 µM was the best minimal concentration for biofilm inhibiting activity. Microscopy analysis demonstrates that pseudonajide interacts with the bacterial cell envelope, disrupting the cell wall and membrane leading to morphological defects in prokaryotes. Conclusions Our results suggest that pseudonajide’s positives charges interacts with negative charged cell wall components of S. epidermidis. Leading to cell damage and biofilm formation inhibition.

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“…Natural peptides are increasingly being explored as alternative biofilm controls, and are sure to become important allies in the fight against bacterial tolerance and resistance ( 15, 44–46 ). As shown here, capsicumicine, a peptide derived from Capsicum baccatum red pepper seeds, possesses strong antibiofilm activity.…”

Section: Discussionmentioning

confidence: 99%

“…Capsicumicine’s amino acid sequence suggested it has a desirable antibiofilm peptide ( 15, 57 ). Furthermore, it contains several residue characteristics for recognizing putative chitin-binding domains, including polar and hydrophobic residue conservation and conserved cysteine residues ( 58–61 ).…”

Section: Discussionmentioning

confidence: 99%

“…Other advantages over planktonic forms include physiological and biochemical changes, beneficial quorum sensing, higher (up to 100 times) mutation rates, and persister cell development ( 10–14 ). Therefore, the development of antivirulence strategies such as efficient antibiofilm agents is crucial for the current antibiotic crisis, and peptides and peptidomimetics are an increasingly important arsenal for controlling pathogenic biofilms ( 15–19 ).…”

Section: Introductionmentioning

confidence: 99%

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First-in-class matrix anti-assembly peptide prevents staphylococcal biofilmin vitroandin vivo

Borowski

Chat

Schneider

et al. 2020

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15 Biofilm-forming bacteria are an important reservoir of nosocomial infections, and source of 16 antibiotic resistance and tolerance. These bacteria are enclosed in a complex matrix that allows 17 them to adhere to medical devices and tissue, and which also protects against antibiotics and 18 immune systems. Advances in antibiofilm strategies for targeting the biofilm matrix are therefore 19 extremely relevant in the fight against multidrug-resistant and/or -tolerant bacteria. Plants are 20 constantly attacked by a wide range of pathogens, and have protective factors such as peptides to 21 defend themselves. These peptides are common components in Capsicum red pepper seeds, and 22here we investigate and identify a new antibiofilm peptide, "capsicumicine." We demonstrate that 23 capsicumicine prevents methicillin-resistant Staphylococcus epidermidis adhesion as well as biofilm 24 establishment and maintenance via a new extracellular "matrix anti-assembly" (MAA) mechanism 25 of action. In this manner, capsicumicine disturbs the construction of the matrix, and therefore its 26 functioning. Importantly, the peptide is not an antibiotic and it is not cytotoxic, thus capsicumicine 27 is an exciting new alternative treatment for prevention of biofilm infections. 28Significance 30 Both pathogenic drug resistance and tolerance are favored by biofilm development. Indeed, biofilm-31 covered microorganisms display antibiotic resistance up to 1000 times higher than planktonic ones. 32Staphylococcus epidermidis is remarkably good at forming biofilm, and is therefore highly associated 33 with medical device infection. Here, we report the discovery of "capsicumicine," a novel antibiofilm 34 peptide derived from Capsicum bacattum. This prevents the establishment of S. epidermidis biofilm 35 via a new mechanism of action, matrix anti-assembly (MAA). MAA is not antibiotic, and is based on 36 extracellular interactions that force bacteria to remain planktonic, letting immune systems and 37 2 traditional antibiotics more easily clear the infection. For this reason, MAA should confer a lower 38 susceptibility to bacterial resistance development. Very importantly, capsicumicine is not cytotoxic. 39 Introduction 40Antimicrobial failure is a worldwide challenge, currently addressed by a WHO global action plan (1). A 41 lack of new antibiotics and the inappropriate use of older treatments mean that multidrug-resistant 42 strains are increasing (2). This process is favored by biofilm development, and microorganisms 43 enclosed in biofilm matrix have antibiotic resistance that is up to 1000 times higher than planktonic 44 ones (3-5). This makes the matrix itself an important target for biofilm control. Biofilms are organized 45 microbial clusters made of a self-assembled matrix that usually attaches to a surface, whether abiotic 46 (medical devices, teeth, etc.) or biotic (host tissues, mucus, inside chronic wounds, etc.) (6, 7). Since 47 the bacteria are embedded into this self-assembled matrix, they are harder to treat because of their 4...

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Peptides as a strategy against biofilm-forming microorganisms: Structure-activity relationship perspectives

Cited by 21 publications

References 101 publications

Promising Antibiofilm Activity of Peptidomimetics

Promising Antibiofilm Activity of Peptidomimetics

Pseudonajide is an antibiotic peptide derived from snake venom that alter cell wall and membrane integrity interfering on biofilm formation.

First-in-class matrix anti-assembly peptide prevents staphylococcal biofilmin vitroandin vivo

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