Prediction and Rational Design of Antimicrobial Peptides

Porto, William F.; Franco, Octávio Luiz

doi:10.5772/38023

Cited by 9 publications

(4 citation statements)

References 41 publications

(70 reference statements)

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“…This agreed with TFE’s known properties for promoting helical structures in peptides [92,93]. Peptide secondary structure was observed by I-TASSER and it has been reported that increased helix propensity also increases antimicrobial potency [94]. AMPs having α-helices are magainin, cecropin and cathelicidin; however, they can perform their functions through interactions with intracellular targets or by disturbing cell processes, as well as inhibiting cell wall, nucleic acid or protein synthesis [95].…”

Section: Discussionsupporting

confidence: 80%

Sarconesin II, a New Antimicrobial Peptide Isolated from Sarconesiopsis magellanica Excretions and Secretions

et al. 2019

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Antibiotic resistance is at dangerous levels and increasing worldwide. The search for new antimicrobial drugs to counteract this problem is a priority for health institutions and organizations, both globally and in individual countries. Sarconesiopsis magellanica blowfly larval excretions and secretions (ES) are an important source for isolating antimicrobial peptides (AMPs). This study aims to identify and characterize a new S. magellanica AMP. RP-HPLC was used to fractionate ES, using C18 columns, and their antimicrobial activity was evaluated. The peptide sequence of the fraction collected at 43.7 min was determined by mass spectrometry (MS). Fluorescence and electronic microscopy were used to evaluate the mechanism of action. Toxicity was tested on HeLa cells and human erythrocytes; physicochemical properties were evaluated. The molecule in the ES was characterized as sarconesin II and it showed activity against Gram-negative (Escherichia coli MG1655, Pseudomonas aeruginosa ATCC 27853, P. aeruginosa PA14) and Gram-positive (Staphylococcus aureus ATCC 29213, Micrococcus luteus A270) bacteria. The lowest minimum inhibitory concentration obtained was 1.9 μM for M. luteus A270; the AMP had no toxicity in any cells tested here and its action in bacterial membrane and DNA was confirmed. Sarconesin II was documented as a conserved domain of the ATP synthase protein belonging to the Fli-1 superfamily. The data reported here indicated that peptides could be alternative therapeutic candidates for use in infections against Gram-negative and Gram-positive bacteria and eventually as a new resource of compounds for combating multidrug-resistant bacteria.

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Section: Discussionsupporting

confidence: 80%

Sarconesin II, a New Antimicrobial Peptide Isolated from Sarconesiopsis magellanica Excretions and Secretions

et al. 2019

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“…Well-constructed AMP databases provide good foundations for AMP prediction. Several prediction approaches have been suggested in recent decades (Porto et al, 2012), using several algorithms (Liu et al, 2017) centered on several parameters. For example, CAMPR3 is developing predictive methods for AMPs that rely on machine learning algorithms such as the random forest (RF), discriminant analysis (DA), and support vector machines (SVMs) (Thomas et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Prediction and Characterization of Cationic Arginine-Rich Plant Antimicrobial Peptide SM-985 From Teosinte (Zea mays ssp. mexicana)

2020

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Antimicrobial peptides (AMPs) are effective against different plant pathogens and newly considered as part of plant defense systems. From prokaryotes to eukaryotes, AMPs can exist in all forms of life. SM-985 is a cationic AMP (CAMP) isolated from the cDNA library of Mexican teosinte (Zea mays ssp. mexicana). A computational prediction server running with different algorithms was used to screen the teosinte cDNA library for AMPs, and the SM-985 peptide was predicted as an AMP with high probability prediction values. SM-985 is an arginine-rich peptide and composed of 21 amino acids (MW: 2671.06 Da). The physicochemical properties of SM-985 are very promising as an AMP, including the net charge (+8), hydrophobicity ratio of 23%, Boman index of 5.19 kcal/mol, and isoelectric point of 12.95. The SM-985 peptide has amphipathic α-helix conformations. The antimicrobial activity of SM-985 was confirmed against six bacterial plant pathogens, and the MIC of SM-985 against Gram-positive indicators was 8 µM, while the MIC of SM-985 against Gram-negative indicators was 4 µM. The SM-985 interacting with the bacterial membrane and this interaction were examined by treatment of the bacterial indicators with FITC-SM-985 peptide, which showed a high binding affinity of SM-985 to the bacterial membrane (whether Gram-positive or Gram-negative). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images of the treated bacteria with SM-985 demonstrated cell membrane damage and cell lysis. In vivo antimicrobial activity was examined, and SM-985 prevented leaf spot disease infection caused by Pst DC3000 on Solanum lycopersicum. Moreover, SM-985 showed sensitivity to calcium chloride salt, which is a common feature of CAMPs.

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“…To this end, antimicrobial peptides (AMPs) are promising as: (1) they typically act by disrupting bacterial membranes instead of inhibiting cellular growth (an unconventional mode of action); (2) they are short and are therefore easy to synthesize; (3) they are biomolecules which naturally results in less environmental toxicity compared to conventional small molecule drugs 3 – 6 . Indeed, several AMPs are now in clinical use including ambicin (nisin), polymixin B and gramicidin S 7 , 8 . However, their therapeutic use has been limited by their cytotoxicity in mammalian cells or their ability to lyse eukaryotic cells 3 , 7 .…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, several AMPs are now in clinical use including ambicin (nisin), polymixin B and gramicidin S 7 , 8 . However, their therapeutic use has been limited by their cytotoxicity in mammalian cells or their ability to lyse eukaryotic cells 3 , 7 .…”

Section: Introductionmentioning

confidence: 99%

Rational design and characterization of cell-selective antimicrobial peptides based on a bioactive peptide from Crocodylus siamensis hemoglobin

Sosiangdi,

Taemaitree,

Tankrathok

et al. 2023

Sci Rep

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Antimicrobial resistance is a growing health concern. Antimicrobial peptides are a potential solution because they bypass conventional drug resistance mechanisms. Previously, we isolated a peptide from Crocodylus siamensis hemoglobin hydrolysate, which has antimicrobial activity and identified the main peptide from this mixture (QL17). The objective of this work was to evaluate and rationally modify QL17 in order to: (1) control its mechanism of action through bacterial membrane disruption; (2) improve its antimicrobial activity; and (3) ensure it has low cytotoxicity against normal eukaryotic cells. QL17 was rationally designed using physicochemical and template-based methods. These new peptide variants were assessed for: (1) their in vitro inhibition of microbial growth, (2) their cytotoxicity against normal cells, (3) their selectivity for microbes, and (4) the mode of action against bacteria using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and confocal microscopy. The results indicate that all designed peptides have more potent antimicrobial efficacy than QL17 and IL15 peptides. However, only the most rationally modified peptides showed strong antimicrobial activity and minimal toxicity against normal cells. In particular, IL15.3 (hydrophobicity of 47% and net charge of + 6) was a potent antimicrobial agent (MIC = 4–12 μg/mL; MBC = 6–25 μg/mL) and displayed excellent selectivity for microbes (cf. human cells) via FACS assays. Microscopy confirmed that IL15.3 acts against bacteria by disrupting the cell membrane integrity and penetrating into the membrane. This causes the release of intracellular content into the outer environment leading to the death of bacteria. Moreover, IL15.3 can also interact with DNA suggesting it could have dual mode of action. Overall, a novel variant of QL17 is described that increases antimicrobial activity by over 1000-fold (~ 5 μg/mL MIC) and has minimal cytotoxicity. It may have applications in clinical use to treat and safeguard against bacteria.

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Prediction and Rational Design of Antimicrobial Peptides

Cited by 9 publications

References 41 publications

Sarconesin II, a New Antimicrobial Peptide Isolated from Sarconesiopsis magellanica Excretions and Secretions

Sarconesin II, a New Antimicrobial Peptide Isolated from Sarconesiopsis magellanica Excretions and Secretions

Prediction and Characterization of Cationic Arginine-Rich Plant Antimicrobial Peptide SM-985 From Teosinte (Zea mays ssp. mexicana)

Rational design and characterization of cell-selective antimicrobial peptides based on a bioactive peptide from Crocodylus siamensis hemoglobin

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