Antimicrobial Peptide Modifications against Clinically Isolated Antibiotic-Resistant Salmonella

Mangmee, Suthee; Reamtong, Onrapak; Kalambaheti, Thareerat; Roytrakul, Sittiruk; Sonthayanon, Piengchan

doi:10.3390/molecules26154654

Cited by 13 publications

(8 citation statements)

References 48 publications

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“…While most known AMPs have a positive net charge (88% of AMPs on the APD3 have a net positive charge; [ 23 ]) only 4 AMPs in the APD3 have a net charge >20 (AP00411, AP00684, AP02232 and AP03367). Cationic AMPs are generally considered to interact with negatively charged bacterial membranes through electrostatic interactions [ 56 ] and, for some modified AMPs, increasing the peptide charge has resulted in more potent antimicrobial activity [ 57 – 59 ]. nAMP-LP-298 (GAGRWRANRRANRRRFARRLRRNQRRAAQKRRAHARRHQRNLRRAARKIRRIQRR-amide; see Table 7 ) was the only peptide tested in this study that displays activity against all bacterial species screened; this may be due to the high peptide charge which could be unravelled through further work.…”

Section: Resultsmentioning

confidence: 99%

Novel integrated computational AMP discovery approaches highlight diversity in the helminth AMP repertoire

Irvine,

McKenzie,

McCoy

et al. 2023

PLoS Pathog

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Antimicrobial Peptides (AMPs) are immune effectors that are key components of the invertebrate innate immune system providing protection against pathogenic microbes. Parasitic helminths (phylum Nematoda and phylum Platyhelminthes) share complex interactions with their hosts and closely associated microbiota that are likely regulated by a diverse portfolio of antimicrobial immune effectors including AMPs. Knowledge of helminth AMPs has largely been derived from nematodes, whereas the flatworm AMP repertoire has not been described. This study highlights limitations in the homology-based approaches, used to identify putative nematode AMPs, for the characterisation of flatworm AMPs, and reveals that innovative algorithmic AMP prediction approaches provide an alternative strategy for novel helminth AMP discovery. The data presented here: (i) reveal that flatworms do not encode traditional lophotrochozoan AMP groups (Big Defensin, CSαβ peptides and Myticalin); (ii) describe a unique integrated computational pipeline for the discovery of novel helminth AMPs; (iii) reveal >16,000 putative AMP-like peptides across 127 helminth species; (iv) highlight that cysteine-rich peptides dominate helminth AMP-like peptide profiles; (v) uncover eight novel helminth AMP-like peptides with diverse antibacterial activities, and (vi) demonstrate the detection of AMP-like peptides from Ascaris suum biofluid. These data represent a significant advance in our understanding of the putative helminth AMP repertoire and underscore a potential untapped source of antimicrobial diversity which may provide opportunities for the discovery of novel antimicrobials. Further, unravelling the role of endogenous worm-derived antimicrobials and their potential to influence host-worm-microbiome interactions may be exploited for the development of unique helminth control approaches.

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Section: Resultsmentioning

confidence: 99%

Novel integrated computational AMP discovery approaches highlight diversity in the helminth AMP repertoire

Irvine,

McKenzie,

McCoy

et al. 2023

PLoS Pathog

View full text Add to dashboard Cite

Antimicrobial Peptides (AMPs) are immune effectors that are key components of the invertebrate innate immune system providing protection against pathogenic microbes. Parasitic helminths (phylum Nematoda and phylum Platyhelminthes) share complex interactions with their hosts and closely associated microbiota that are likely regulated by a diverse portfolio of antimicrobial immune effectors including AMPs. Knowledge of helminth AMPs has largely been derived from nematodes, whereas the flatworm AMP repertoire has not been described. This study highlights limitations in the homology-based approaches, used to identify putative nematode AMPs, for the characterisation of flatworm AMPs, and reveals that innovative algorithmic AMP prediction approaches provide an alternative strategy for novel helminth AMP discovery. The data presented here: (i) reveal that flatworms do not encode traditional lophotrochozoan AMP groups (Big Defensin, CSαβ peptides and Myticalin); (ii) describe a unique integrated computational pipeline for the discovery of novel helminth AMPs; (iii) reveal >16,000 putative AMP-like peptides across 127 helminth species; (iv) highlight that cysteine-rich peptides dominate helminth AMP-like peptide profiles; (v) uncover eight novel helminth AMP-like peptides with diverse antibacterial activities, and (vi) demonstrate the detection of AMP-like peptides from Ascaris suum biofluid. These data represent a significant advance in our understanding of the putative helminth AMP repertoire and underscore a potential untapped source of antimicrobial diversity which may provide opportunities for the discovery of novel antimicrobials. Further, unravelling the role of endogenous worm-derived antimicrobials and their potential to influence host-worm-microbiome interactions may be exploited for the development of unique helminth control approaches.

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“…While most known AMPs have a positive net charge [88% of AMPs on the APD3 have a net positive charge; 23] only 4 AMPs in the APD3 have a net charge >20 (AP00411, AP00684, AP02232 and AP03367). Cationic AMPs are generally considered to interact with negatively charged bacterial membranes through electrostatic interactions [54] and, for some modified AMPs, increasing the peptide charge has resulted in more potent antimicrobial activity [55-57]. nAMP-LP-298 (GAGRWRANRRANRRRFARRLRRNQRRAAQKRRAHARRHQRNLRRAARKIRRIQRR-amide; see Table 7) was only peptide tested in this study that displays activity against all bacterial species screened; this may be due to the high peptide charge which could be unravelled through further work.…”

Section: Resultsmentioning

confidence: 99%

Novel integrated computational AMP discovery approaches highlight diversity in the helminth AMP repertoire

Irvine

Mckenzie

McCoy

et al. 2023

Preprint

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Antimicrobial Peptides (AMPs) are immune effectors that are key components of the invertebrate innate immune system providing protection against pathogenic microbes. Parasitic helminths share complex interactions with their hosts and closely associated microbiota that are likely regulated by a diverse portfolio of antimicrobial immune effectors including AMPs. Knowledge of helminth AMPs has largely been derived from nematodes, whereas the flatworm AMP repertoire has not been described.This study highlights limitations in the homology-based approaches, used to identify putative nematode AMPs, for the characterisation of flatworm AMPs, and reveals that innovative algorithmic AMP prediction approaches provide an alternative strategy for novel helminth AMP discovery. The data presented here: (i) reveal that flatworms do not encode traditional lophotrochozoan AMP groups (Big Defensin, CSαβ peptides and Myticalin); (ii) describe a unique integrated computational pipeline for the discovery of novel helminth AMPs; (iii) reveal >16,000 putative AMP-like peptides across 127 helminth species; (iv) highlight that cysteine-rich peptides dominate helminth AMP-like peptide profiles; (v) uncover eight novel helminth AMP-like peptides with diverse antibacterial activities, and (vi) demonstrate the detection of AMP-like peptides from helminth biofluids. These data represent a significant advance in our understanding of the putative helminth AMP repertoire and underscore a potential untapped source of antimicrobial diversity which may provide opportunities for the discovery of novel antimicrobials. Further, unravelling the role of endogenous worm-derived antimicrobials and their potential to influence host-worm-microbiome interactions may be exploited for the development of unique helminth control approaches.Author summaryInvertebrate antimicrobial peptides (AMPs) form the first line of defence against pathogenic microbes. Helminths are worms (flatworm, roundworm) that live in microbe-rich environments throughout their lifecycles however little is known about how they protect themselves against pathogens or how they interact with microbes. Understanding AMP profiles in helminths, their importance to helminth biology, and how they shape microbial communities could reveal novel approaches for anthelmintic and/or antimicrobial development.In this study we describe a novel integrated homology- and computational-based pipeline for the discovery of helminth AMPs. This approach revealed that, whilst flatworms do not possess traditional AMPs, they have a repertoire of unique AMP-like peptides that are predominantly cysteine-rich. Significantly eight novel helminth AMP-like peptides, discovered using this pipeline, have antibacterial activities against a range of bacteria highlighting their potential as novel antimicrobials. Further, peptidomics analyses demonstrate the presence of AMP-like peptides in helminth body fluids supporting the need to further characterise these peptides and their function(s) in helminths. These data present novel opportunities to better understand helminth biology, discover new antimicrobials and develop future control strategies for helminth parasites.

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“…The screening of derivatives from the AMP D51 against Bacillus cereus (a food poisoning bacterium) highlighted the peptides D51-P11G and D51-P11K for their anti-spore germination and anti-biofilm activities, which they instigated via membrane lysis [93]. Peptide variants of BmKn-2 from scorpion venom exhibited anti-biofilm activity against Salmonella isolates [94]. With respect to oral health, Jiang et al showed that AMP DP7 inhibited planktonic and biofilm forms of Porphyromonas gingivalis [95].…”

Section: Fungimentioning

confidence: 99%

A Comprehensive Review of Recent Research into the Effects of Antimicrobial Peptides on Biofilms—January 2020 to September 2023

Fontanot,

Ellinger,

Unger

et al. 2024

Antibiotics

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Microbial biofilm formation creates a persistent and resistant environment in which microorganisms can survive, contributing to antibiotic resistance and chronic inflammatory diseases. Increasingly, biofilms are caused by multi-drug resistant microorganisms, which, coupled with a diminishing supply of effective antibiotics, is driving the search for new antibiotic therapies. In this respect, antimicrobial peptides (AMPs) are short, hydrophobic, and amphipathic peptides that show activity against multidrug-resistant bacteria and biofilm formation. They also possess broad-spectrum activity and diverse mechanisms of action. In this comprehensive review, 150 publications (from January 2020 to September 2023) were collected and categorized using the search terms ‘polypeptide antibiotic agent’, ‘antimicrobial peptide’, and ‘biofilm’. During this period, a wide range of natural and synthetic AMPs were studied, of which LL-37, polymyxin B, GH12, and Nisin were the most frequently cited. Furthermore, although many microbes were studied, Staphylococcus aureus and Pseudomonas aeruginosa were the most popular. Publications also considered AMP combinations and the potential role of AMP delivery systems in increasing the efficacy of AMPs, including nanoparticle delivery. Relatively few publications focused on AMP resistance. This comprehensive review informs and guides researchers about the latest developments in AMP research, presenting promising evidence of the role of AMPs as effective antimicrobial agents.

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Antimicrobial Peptide Modifications against Clinically Isolated Antibiotic-Resistant Salmonella

Cited by 13 publications

References 48 publications

Novel integrated computational AMP discovery approaches highlight diversity in the helminth AMP repertoire

Novel integrated computational AMP discovery approaches highlight diversity in the helminth AMP repertoire

Novel integrated computational AMP discovery approaches highlight diversity in the helminth AMP repertoire

A Comprehensive Review of Recent Research into the Effects of Antimicrobial Peptides on Biofilms—January 2020 to September 2023

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