耐性菌に対する抗生物質の効力を回復させる抗菌素材(Antibacterial material restores the efficacy of antibiotics against resistant bacteria)

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2024-11-18 チャルマース工科大学

スウェーデンのチャルマース工科大学の研究により、抗菌ペプチドを含むハイドロゲル素材が、抗生物質耐性菌に対する抗生物質の効果を回復させることが明らかになりました。この素材は、メチシリン耐性黄色ブドウ球菌(MRSA)などの耐性菌に対して、オキサシリンとの併用で64倍の効果増強を示しました。ハイドロゲルは安定性が高く、局所的な適用が可能で、副作用も少ないため、創傷治療などへの応用が期待されています。

<関連情報>

抗菌ペプチド機能化ハイドロゲル粒子とバンコマイシンおよびオキサシリン抗生物質との併用による抗菌効果 Antibacterial efficacy of antimicrobial peptide-functionalized hydrogel particles combined with vancomycin and oxacillin antibiotics

Annija Stepulane, Anand Kumar Rajasekharan, Martin Andersson
International Journal of Pharmaceutics  Available online: 30 August 2024
DOI:https://doi.org/10.1016/j.ijpharm.2024.124630

Graphical abstract

耐性菌に対する抗生物質の効力を回復させる抗菌素材(Antibacterial material restores the efficacy of antibiotics against resistant bacteria)

Abstract

The rise of antibiotic resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), requires novel approaches to combat infections. Medical devices like implants and wound dressings are frequently used in conjunction with antibiotics, motivating the development of antibacterial biomaterials capable of exhibiting combined antibacterial effects with conventional antibiotics. This study explores the synergistic antibacterial effects of combining antimicrobial peptide (AMP) functionalized hydrogel particles with conventional antibiotics, vancomycin (VCM) and oxacillin (OXA), against Staphylococcus aureus and MRSA. The AMP employed, RRPRPRPRPWWWW-NH2, has previously demonstrated broad-spectrum activity and enhanced stability when attached to hydrogel substrates. Here, checkerboard assays revealed additive and synergistic interactions between the free AMP and both VCM and OXA against Staphylococcus aureus and MRSA. Notably, the AMP-OXA combination displayed a significant synergistic effect against MRSA, with a 512-fold reduction in OXA’s minimum inhibitory concentration (MIC) when combined with free AMP. The observed synergism against MRSA was retained upon covalent AMP immobilization onto the hydrogel particles; however, at a lower rate with a 64-fold reduction in OXA MIC. Despite this, the OXA-AMP hydrogel particle combinations retained considerable synergistic potential against MRSA, a strain resistant to OXA, highlighting the potential of AMP-functionalized materials for enhancing antibiotic efficacy. These findings underscore the importance of developing antimicrobial biomaterials for future medical devices to fight biomaterial-associated infections and reverse antimicrobial resistance.

抗菌ペプチドハイドロゲル創傷被覆材の無傷皮膚への使用に関する臨床試験 Clinical investigation of use of an antimicrobial peptide hydrogel wound dressing on intact skin

Edvin Blomstrand,Saba Atefyekta,Anand K Rajasekharan,Martin Andersson
Journal of Wound Care  Published:10 Jun 2023
DOI:https://doi.org/10.12968/jowc.2023.32.6.368

Abstract

A material with the ability to rapidly eradicate bacteria via a contact-killing mechanism has the benefit of a more localised treatment that is easy to implement when needed to prevent or treat a bacterial infection. Here, we present an antimicrobial material based on covalently attached antimicrobial peptides (AMPs) to a soft amphiphilic hydrogel. This results in a material that exhibits an antimicrobial effect based on contact-killing. In this study, the antimicrobial efficacy of the AMP-hydrogel was investigated by observing the changes in total bioburden on the intact skin of healthy human volunteers when the AMP-hydrogel dressing was placed on the forearm for three hours. The AMP-hydrogel significantly reduced the bioburden on the skin from a mean value of 1200CFU/cm2 for the untreated skin to 23CFU/cm2. Biocompatibility evaluations of the AMP-hydrogel showed no sign of cytotoxicity, acute systemic toxicity, irritation or sensitisation, demonstrating the safety of the AMP-hydrogel as a potential wound dressing. Leachability studies confirmed no release of AMPs and that the antimicrobial effect was localised to the surface of the hydrogels, demonstrating a pure contact-killing mode of action.

有機化学・薬学
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