Editorial: Insights in antimicrobials, resistance, and chemotherapy: 2021

Aminov, Rustam

doi:10.3389/fmicb.2022.1037326

Cited by 3 publications

(2 citation statements)

References 6 publications

(6 reference statements)

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“…AMPs combine the advantages of vaccines’ specificity and antibiotics’ high activity in the iron triangle cooperation form, while avoiding their disadvantages of being energy expending and causing pathogen mutation, drug residues and resistance. This is due to the unique enzyme sensitivity of AMPs that results in their easy degradation, but it is also this property that limits their clinical translation to oral and intravenous formulations [ 12 , 13 , 14 , 15 ]. AMPs promote epidermal cell growth, repair the cortex and have anti-inflammatory properties [ 16 , 17 ], making AMPs a potential topical drug.…”

Section: Introductionmentioning

confidence: 99%

Efficiency of NZ2114 on Superficial Pyoderma Infected with Staphylococcus pseudintermedius

Yang,

Huang,

et al. 2024

Pharmaceuticals

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Staphylococcus pseudintermedius (S. pseudintermedius) is the main pathogen causing pyoderma of canines. With the emergence of drug-resistant bacteria, traditional antibiotic treatments are limited. As a potential antibacterial agent, NZ2114 was effective against S. pseudintermedius, including drug-resistant strains. Its bactericidal efficacy was superior to mupiroxacin, ofloxacin and lincomycin. To facilitate the transcutaneous delivery of NZ2114 for the treatment of superficial pyoderma, chemical permeation enhancers were added since water-soluble NZ2114 does not easily penetrate the skin lipid layer. Two different NZ2114 sprays were prepared by combining 1% Azone + 10% propylene glycol (PG) or 5% N-methylpyrrolidone (NMP) + 10% PG with NZ2114 after screening. The cumulative permeability of NZ2114 sprays were 244.149 and 405.245 μg/cm2 at 24 h with an in vitro percutaneous assay of mice skin, which showed a 244% and 405% increase in skin permeability than NZ2114, respectively. In addition, the efficacy of NZ2114 sprays in reducing skin bacteria colonisation was demonstrated in a mouse model of superficial pyoderma (24 mice, 3 mice/group) induced by S. pseudintermedius, and the 5% NMP + 10% PG + NZ2114 group had the best therapeutic effect compared to the other groups. This preparation did not cause any skin irritation, laying the foundation for the development of an effective and non-toxic topical product.

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Section: Introductionmentioning

confidence: 99%

Efficiency of NZ2114 on Superficial Pyoderma Infected with Staphylococcus pseudintermedius

Yang,

Huang,

et al. 2024

Pharmaceuticals

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“…In another aspect, AMPs are from innate defensing system with natural compatibility in body playing as a role of peace keeper during daily health maintenance unlike the traditional antibiotics and chemical drugs specially for overcoming intensive pathogens and severe infections usually with the obvious side effects as residual, cytotoxic, resistance and others via role of heavy weapons or killers; In fact, the former is usually more important than the latter as a whole on purpose of green health, and they are connected each other closely via a balance keeping attributing into the same goal, it is of unique great importance especially under the almost dry or empty pipeline of new drug R & D for years; Corresponding, the iron triangle theory of the health protection built by AMPs, vaccines, and antibiotics is conducive to maintaining a reasonable balance among pathogens, antimicrobial agents, and drug-resistance (Hao et al, 2022). However, AMPs also have some drawbacks, such as low stability due to enzyme sensitivity, high toxicity, and low bioavailability (Wang et al, 2021;Aminov, 2022). The instability of AMPs is a major impediment to their entry into clinical studies, especially the enzymatic sensitivity of peptides that are extremely susceptible to degradation by proteases in the gastrointestinal (GI) tract and tissue proteolysis when injected, which limits their oral and intravenous availability.…”

Section: Introductionmentioning

confidence: 99%

Plectasin: from evolution to truncation, expression, and better druggability

Li,

Hao,

Yang

et al. 2023

Front. Microbiol.

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Non-computational classical evolution analysis of plectasin and its functional relatives can especially contribute tool value during access to meet requirements for their better druggability in clinical use. Staphylococcus aureus is a zoonotic pathogen that can infect the skin, blood, and other tissues of humans and animals. The impact of pathogens on humans is exacerbated by the crisis of drug resistance caused by the misuse of antibiotics. In this study, we analyzed the evolution of anti-Staphylococcus target functional sequences, designed a series of plectasin derivatives by truncation, and recombinantly expressed them in Pichia pastoris X-33, from which the best recombinant Ple-AB was selected for the druggability study. The amount of total protein reached 2.9 g/L following 120 h of high-density expression in a 5-L fermenter. Ple-AB was found to have good bactericidal activity against gram-positive bacteria, with minimum inhibitory concentration (MIC) values ranging between 2 and 16 μg/mL. It showed good stability and maintained its bactericidal activity during high temperatures, strong acid and alkali environments. Notably, Ple-AB exhibited better druggability, including excellent trypsin resistance, and still possessed approximately 50% of its initial activity following exposure to simulated intestinal fluids for 1 h. In vitro safety testing of Ple-AB revealed low hemolytic activity against mouse erythrocytes and cytotoxicity against murine-derived macrophages. This study successfully realized the high expression of a new antimicrobial peptide (AMP), Ple-AB, in P. pastoris and the establishment of its oral administration as an additive form with high trypsin resistance; the study also revealed its antibacterial properties, indicating that truncation design is a valuable tool for improving druggability and that the candidate Ple-AB may be a novel promising antimicrobial agent.

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