Design, optimization, and nanotechnology of antimicrobial peptides: From exploration to applications

Tan, Peng; Fu, Hong; Ma, Xi

doi:10.1016/j.nantod.2021.101229

Cited by 184 publications

(132 citation statements)

References 308 publications

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“…Because of the special membrane active action and antimicrobial performance, AMPs are increasingly becoming the hot topic at the field of antibiotic candidates in fighting against the emerging drug resistant bacterial infection ( del Rosso et al, 2019 ; Zhang et al, 2020 ). Although the antimicrobial performance and research potency are promising, the clinical application of AMPs still faces great challenges such as manufacturing costs, safety, bioactivity, rational design strategy, and so on ( Tan et al, 2021 ; Wang et al, 2021 ), which makes it important to explore the novel design strategy to design AMPs with high cell selectivity ( Shao et al, 2020 ). It has been well discussed that the Trp residues played an important role in the antimicrobial activity of linear a-helical antimicrobial peptide by deeply inserting into the negatively charged bacterial membrane, and the penetration of AMPs into the bacterial membrane could be enhanced without causing obvious binding activity to the membrane of mammalian cells when the Trp residues occurred at the hydrophobic-hydrophilic interface ( Song et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

The Trp-rich Antimicrobial Amphiphiles With Intramolecular Aromatic Interactions for the Treatment of Bacterial Infection

Wang

et al. 2021

Front. Microbiol.

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Antibiotic resistance is emerging as a hot issue with the abuse and overuse of antibiotics, and the shortage of effective antimicrobial agents against multidrug resistant bacteria creates a huge problem to treat the threatening nosocomial skin and soft tissue infection. Antimicrobial peptides (AMPs) exhibite enormous potential as one of the most promising candidates of antibiotic to fight against pathogenic infections because of its unique membrane penetration mechanism to kill pathogens, whereas the clinical application of AMPs still faces the challenges of production cost, stability, safety, and design strategy. Herein, a series of Trp-rich peptides was designed following the principle of paired Trp plated at the ith and ith+4 position on the backbone of peptides, based on the template (VKKX)4, where X represents W, A, or L, to study the effect of intramolecular aromatic interactions on the bioactivity of AMPs. Through comparing the antimicrobial performance, hemolysis, cytotoxicity, and stability, VW5 which is equipped with the characters of direct antimicrobial efficacy (GM=1.68μM) and physical destruction of bacterial membrane (SEM and electron microscopy) stood out from the engineering peptides. VW5 also performed well in mice models, which could significantly decrease the bacterial colony (VW5 vs infection group, 12.72±2.26 vs 5.52±2.01×109CFU/abscess), the area of dermo-necrosis (VW5 vs infection group, 0.74±0.29 vs 1.86±0.98mm2) and the inflammation cytokine levels at the abscess site without causing toxicity to the skin. Overall, this study provides a strategy and template to diminish the randomness in the exploration and design of novel peptides.

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Section: Discussionmentioning

confidence: 99%

The Trp-rich Antimicrobial Amphiphiles With Intramolecular Aromatic Interactions for the Treatment of Bacterial Infection

Wang

et al. 2021

Front. Microbiol.

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“…However, there are only a few available for clinical use, such as bacitracin and polymyxin [ 36 ]. Antimicrobial peptides are easily degraded by protease and lose their antibacterial activity, which leads to the limitations of clinical application [ 3 ]. Among them, trypsin is a very important digestive enzyme ubiquitous in mammals, which mainly attacks the arginine and lysine of proteins or polypeptides [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…The emergence of new antibiotic-resistant bacteria means that clinical treatment is facing a great crisis. Therefore, the development of new antibacterial agents has become an urgent task [ 3 ]. Antimicrobial peptides (AMPs) are considered ideal candidates to replace antibiotics because of their strong potential against multidrug-resistant bacteria and their unique mechanism of action; that is these peptides are currently the main focus of research [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the development of new antibacterial agents has become an urgent task [ 3 ]. Antimicrobial peptides (AMPs) are considered ideal candidates to replace antibiotics because of their strong potential against multidrug-resistant bacteria and their unique mechanism of action; that is these peptides are currently the main focus of research [ 3 , 4 , 5 ]. At present, most of the studies on antimicrobial peptides have focused on finding new peptides with good activity, but few studies have focused on their behavior in the clinical environment [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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An Antibacterial Peptide with High Resistance to Trypsin Obtained by Substituting d-Amino Acids for Trypsin Cleavage Sites

et al. 2021

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The poor stability of antibacterial peptide to protease limits its clinical application. Among these limitations, trypsin mainly exists in digestive tract, which is an insurmountable obstacle to orally delivered peptides. OM19R is a random curly polyproline cationic antimicrobial peptide, which has high antibacterial activity against some gram-negative bacteria, but its stability against pancreatin is poor. According to the structure-activity relationship of OM19R, all cationic amino acid residues (l-arginine and l-lysine) at the trypsin cleavage sites were replaced with corresponding d-amino acid residues to obtain the designed peptide OM19D, which not only maintained its antibacterial activity but also enhanced the stability of trypsin. Proceeding high concentrations of trypsin and long-time (such as 10 mg/mL, 8 h) treatment, it still had high antibacterial activity (MIC = 16–32 µg/mL). In addition, OM19D also showed high stability to serum, plasma and other environmental factors. It is similar to its parent peptide in secondary structure and mechanism of action. Therefore, this strategy is beneficial to improve the protease stability of antibacterial peptides.

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“…Futhermore, Thr supplementation may suppress the inflammatory cytokine synthesis by inhibiting the TLR4 signal pathway to improve intestinal immune function [7]. Antimicrobial peptides in the gut also contribute to the intestinal immune response [102]. A recent study found that L-Thr at the concentration of 1mM upregulates β-defensin (pBD-1, pBD-2, and pBD-3) expression by activating NF-κB signaling and inhibiting sirtuin-1 (SIRT1) expression in porcine intestinal epithelial cells [103].…”

Section: Immune Functionmentioning

confidence: 99%

Physiological Functions of Threonine in Animals: Beyond Nutrition Metabolism

Tang

Tan

et al. 2021

Nutrients

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Threonine (Thr), an essential amino acid for animals and the limiting amino acid in swine and poultry diets, which plays a vital role in the modulation of nutritional metabolism, macromolecular biosynthesis, and gut homeostasis. Current evidence supports that the supplementation of Thr leads to benefits in terms of energy metabolism. Threonine is not only an important component of gastrointestinal mucin, but also acts as a nutritional modulator that influences the intestinal immune system via complex signaling networks, particularly mitogen-activated protein kinase (MAPK) and the target of the rapamycin (TOR) signal pathway. Threonine is also recognized as an indispensable nutrient for cell growth and proliferation. Hence, optimization of Thr requirement may exert a favorable impact on the factors linked to health and diseases in animals. This review focuses on the latest reports of Thr in metabolic pathways and nutritional regulation, as well as the relationship between Thr and relevant physiological functions.

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Design, optimization, and nanotechnology of antimicrobial peptides: From exploration to applications

Cited by 184 publications

References 308 publications

The Trp-rich Antimicrobial Amphiphiles With Intramolecular Aromatic Interactions for the Treatment of Bacterial Infection

The Trp-rich Antimicrobial Amphiphiles With Intramolecular Aromatic Interactions for the Treatment of Bacterial Infection

An Antibacterial Peptide with High Resistance to Trypsin Obtained by Substituting d-Amino Acids for Trypsin Cleavage Sites

Physiological Functions of Threonine in Animals: Beyond Nutrition Metabolism

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