pH Dependence of Microbe Sterilization by Cationic Antimicrobial Peptides

Walkenhorst, William F.; Klein, J. Wolfgang; Vo, Phuong; Wimley, William C.

doi:10.1128/aac.00063-13

Cited by 57 publications

(49 citation statements)

References 55 publications

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“…These observations clearly suggest that when characterizing the antimicrobial action of AMPs, the optimal pH for their action against individual microbes should be determined. This point is well illustrated by recent studies, which investigated the antimicrobial action of a range of synthetic AMPs and found that high pH inhibited the action of these peptides against fungi and Gram-negative bacteria but the opposite pH trend was observed for Gram-positive bacteria [302]. …”

Section: Discussionmentioning

confidence: 75%

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

et al. 2016

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Antimicrobial peptides (AMPs) are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations and hydrogel delivery systems. Nonetheless, many pH dependent AMPs and antimicrobial proteins have yet to be fully characterized and these molecules, as a whole, represent an untapped source of novel biologically active agents that could aid fulfillment of the urgent need for alternatives to conventional antibiotics, helping to avert a return to the pre-antibiotic era.

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Section: Discussionmentioning

confidence: 75%

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

et al. 2016

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“…In the case of His-containing peptides, the enhancement occurs due to an increase in peptide net charge and a facilitated translocation (Kacprzyk et al, 2007). This hypothesis is well illustrated in recent studies showing that high pH inhibited the antifungal activity of synthetic peptides (Walkenhorst, Klein, Vo, & Wimley, 2013), although some peptides display better activity at higher pH (Hajji et al, 2010). In order to provide a larger pH range, dimers (P-113) can be created, although a deeper understanding of the effect on peptide antifungal activity is needed.…”

Section: Effect Of Temperature Ph and Proteolysismentioning

confidence: 71%

Natural Antifungal Peptides/Proteins as Model for Novel Food Preservatives

Thery

Lynch

Arendt

2019

Comp Rev Food Sci Food Safe

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A large range of ingredients for food and food products are subject to fungal contamination, which is a major cause of destruction of crops, exposure of animals and humans to invasive mycotoxins, and food spoilage. The resistance of fungal species to common preservation methods highlights the necessity of new ways to increase the shelf life of raw material for food and food products. Antimicrobial peptides and proteins (AMPs) are essential members of the immune system of most living organisms. Due to their broad range of activity and their stability to commonly used food processes, they represent promising alternatives to traditional preservatives. However, despite the growing number of reports of potential food applications of these AMPs, the number of approved peptides is low. Poor solubility, toxicity, and a time‐consuming extraction are hurdles that limit their application in food products. Thanks to a deep understanding of the key determinants of their activity, the development of optimized synthetic peptides has reduced these drawbacks. This review presents natural and synthetic antifungal peptides/proteins (AFPs), effective against food‐related fungi, with particular emphasis on AFPs from plant sources. The design of novel antifungal peptides via key elements of antifungal activity is also reviewed. The potential applications of natural and synthetic AFPs as novel antifungal food preservatives are finally discussed.

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“…In contrast, salt and serum had clear effects on the activity of other AMPs such as human beta defensin 3 (hBD-3). 42, 43 …”

Section: Resultsmentioning

confidence: 99%

Small lipopeptides possess anti-biofilm capability comparable to daptomycin and vancomycin

2015

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Antibiotic resistance, to a large extent, is related to the formation of bacterial biofilms. Thus, compounds with anti-biofilm capability are of practical importance. Inspired by the recent discovery of two amino acid lipopeptides from marine bacteria, we constructed a family of small lipopeptides with 2-3 amino acids. While no antimicrobial activity was found for anionic lipopeptides, cationic candidates are potent against Staphylococcus strains, such as methicillin-resistant Staphylococcus aureus (MRSA) USA200, USA300, USA400, UAMS-1, Newman, and Mu50. In the simplest design, two lysines (C14-KK) or three arginines (C14-RRR) attached to an acyl chain of 14 carbons were sufficient to make the compounds antimicrobial. These simple lipopeptides are inherently stable towards S. aureus V8 proteinase and fungal proteinase K, more soluble in water, and more selective than other lipopeptides containing a mixture of hydrophobic and cationic amino acids. Furthermore, the activity of C14-RRR was not compromised by salts, serum, or a change in pH. Live cell experiments revealed that these lipopeptides, with a detergent-like structure, killed bacteria rapidly by targeting cell membranes. Importantly, these compounds were also able to inhibit biofilm formation and could even disrupt preformed biofilms of clinically relevant MRSA strains with an in vitro efficacy comparable to daptomycin and vancomycin. These results indicate that small lipopeptides are potentially useful candidates for preventing or eliminating bacterial biofilms alone or in combination with daptomycin or vancomycin.

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pH Dependence of Microbe Sterilization by Cationic Antimicrobial Peptides

Cited by 57 publications

References 55 publications

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

Natural Antifungal Peptides/Proteins as Model for Novel Food Preservatives

Small lipopeptides possess anti-biofilm capability comparable to daptomycin and vancomycin

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