A How-To Guide for Mode of Action Analysis of Antimicrobial Peptides

Schäfer, Ann-Britt; Wenzel, Michaela

doi:10.3389/fcimb.2020.540898

Cited by 37 publications

(41 citation statements)

References 283 publications

(431 reference statements)

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“…A recent increase in antibiotic-resistant bacteria strains has driven researchers to develop new methods and devices that can correctly guide a physician to the most efficient antibiotic for a specific infection [1][2][3]. The need to rapidly identify and start treatment of infections becomes critical to avoid serious consequences for patients [4].…”

Section: Introductionmentioning

confidence: 99%

A novel, time-effective approach for capturing bacteria from contaminated urine samples

Ierardi¹,

Domenichini²,

Vercellotti³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background: A fundamental step in the race to design a rapid diagnostic test for antimicrobial resistance is the separation of bacteria from their matrix. Many recent studies have been focused on the development of systems capable of separating and capturing bacteria from liquid environments. Methods: Herein, we introduce a new approach to this issue by using the natural bacteria tendency to accumulate at naturally-occurring interfaces, such as liquid-gas and liquid-solid interfaces, where also organic molecules like lipids, proteins, and polysaccharides accumulate. This bacterial behavior leads to the formation of a superficial layer close to the interface rich in bacteria, from which it is possible to capture a consistent amount of bacteria by means of surfaces with high chemical affinity to the outer bacteria surface. Results: This paper demonstrates how to capture bacteria from contaminated urine samples, by means of commercial microscope slides coated with positively charged biomolecules, without the utilization of the bacterial culture step for multiplying the bacteria. Conclusions: This approach is an easy, quick and economical method to concentrate living bacteria in a well-defined position onto a microscope slide, thus making them easily available for further diagnostic investigations.

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Section: Introductionmentioning

confidence: 99%

A novel, time-effective approach for capturing bacteria from contaminated urine samples

Ierardi¹,

Domenichini²,

Vercellotti³

et al. 2022

Front. Biosci. (Landmark Ed)

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“…The first category is characterized by direct and severe damage of the membrane, which rapidly leads to cell lysis and bacterial death. Such AMPs are called either "pore-former" [18], "lytic" [19], "membrane-damaging" [20], "membrane-active" [21], or "membrane-disruptive" peptides [11]. Several mechanisms of action have been proposed, mainly explored on model membranes [18,22], and particularly for linear helical AMPs.…”

Section: Introductionmentioning

confidence: 99%

“…The second category presupposes rapid translocation of the AMP through the membrane without directly destroying it. It employs a wide variety of mechanisms, which have been scarcely studied and are therefore still poorly understood [21]. In such cases, interaction with bacterial cell surface remains an essential initial step of the global process of bacteria killing, but membranes are not the main targets [18,19,[21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Real-Time Fluorescence Microscopy on Living E. coli Sheds New Light on the Antibacterial Effects of the King Penguin β-Defensin AvBD103b

Landon

Zhu

Mustafi

et al. 2022

IJMS

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(1) Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics. Among AMPs, the disulfide-rich β-defensin AvBD103b, whose antibacterial activities are not inhibited by salts contrary to most other β-defensins, is particularly appealing. Information about the mechanisms of action is mandatory for the development and approval of new drugs. However, data for non-membrane-disruptive AMPs such as β-defensins are scarce, thus they still remain poorly understood. (2) We used single-cell fluorescence imaging to monitor the effects of a β-defensin (namely AvBD103b) in real time, on living E. coli, and at the physiological concentration of salts. (3) We obtained key parameters to dissect the mechanism of action. The cascade of events, inferred from our precise timing of membrane permeabilization effects, associated with the timing of bacterial growth arrest, differs significantly from the other antimicrobial compounds that we previously studied in the same physiological conditions. Moreover, the AvBD103b mechanism does not involve significant stereo-selective interaction with any chiral partner, at any step of the process. (4) The results are consistent with the suggestion that after penetrating the outer membrane and the cytoplasmic membrane, AvBD103b interacts non-specifically with a variety of polyanionic targets, leading indirectly to cell death.

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“…Recent advances in microscopy technology and cell biological labeling techniques allow studying mechanisms of AMPs in unprecedented detail. The review of Schäfer and Wenzel [152] gives an overview of available in vivo methods to investigate the antibacterial mechanisms of AMPs. They discuss global profiling techniques, such as genomic and proteomic approaches, as well as bacterial cytological profiling and other cell biological assays and cover recent approaches to determine the effects of AMPs on cell morphology, outer membrane, cell wall, and inner membrane properties, cellular macromolecules, and protein targets.…”

Section: Introduction Of Protective Groups Non-natural Amino Acids and Cyclization: Combination Of Derivatizations And Hybrid Peptidesmentioning

confidence: 99%

Discovery, Optimization, and Clinical Application of Natural Antimicrobial Peptides

et al. 2021

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Antimicrobial peptides (AMPs) are widespread in multicellular organisms. These structurally diverse molecules are produced as the first line of defense against pathogens such as bacteria, viruses, fungi, and parasites. Also known as host defense peptides in higher eukaryotic organisms, AMPs display immunomodulatory and anticancer activities. During the last 30 years, technological advances have boosted the research on antimicrobial peptides, which have also attracted great interest as an alternative to tackling the antimicrobial resistance scenario mainly provoked by some bacterial and fungal pathogens. However, the introduction of natural AMPs in clinical trials faces challenges such as proteolytic digestion, short half-lives, and cytotoxicity upon systemic and oral application. Therefore, some strategies have been implemented to improve the properties of AMPs aiming to be used as effective therapeutic agents. In the present review, we summarize the discovery path of AMPs, focusing on preclinical development, recent advances in chemical optimization and peptide delivery systems, and their introduction into the market.

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A How-To Guide for Mode of Action Analysis of Antimicrobial Peptides

Cited by 37 publications

References 283 publications

A novel, time-effective approach for capturing bacteria from contaminated urine samples

A novel, time-effective approach for capturing bacteria from contaminated urine samples

Real-Time Fluorescence Microscopy on Living E. coli Sheds New Light on the Antibacterial Effects of the King Penguin β-Defensin AvBD103b

Discovery, Optimization, and Clinical Application of Natural Antimicrobial Peptides

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