Arcopilins: A New Family of Staphylococcus aureus Biofilm Disruptors from the Soil Fungus Arcopilus navicularis,Journal of Medicinal Chemistry

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Arcopilins: A New Family of Staphylococcus aureus Biofilm Disruptors from the Soil Fungus Arcopilus navicularis
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2024-08-14 , DOI: 10.1021/acs.jmedchem.4c00585
Esteban Charria-Girón _{1,

2} , Haoxuan Zeng _{1,

2} , Tatiana E Gorelik _{3,

4} , Alexandra Pahl ₁ , Khai-Nghi Truong ₅ , Hedda Schrey _{1,

2} , Frank Surup _{1,

2} , Yasmina Marin-Felix _{1,

2}

Affiliation

Biofilms represent a key challenge in the treatment of microbial infections; for instance, Staphylococcus aureus causes chronic or fatal infections by forming biofilms on medical devices. Herein, the fungus Arcopilus navicularis was found to produce a novel family of PKS-NRPS metabolites that are able to disrupt preformed biofilms of S. aureus. Arcopilins A–F (1–6), tetramic acids, and arcopilin G (7), a 2-pyridone, were elucidated using HR-ESI-MS and one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy. Their absolute configuration was established by the synthesis of MPTA-esters for 2, analysis of ¹H–¹H coupling constants, and ROESY correlations, along with comparison with the crystal structure of 7. Arcopilin A (1) not only effectively disrupts preformed biofilms of S. aureus but also potentiates the activity of gentamicin and vancomycin up to 115- and 31-fold times, respectively. Our findings demonstrate the potential application of arcopilins for the conjugated treatment of infections caused by S. aureus with antibiotics unable to disrupt preformed biofilms.

中文翻译：

Arcopilins：来自土壤真菌 Arcopilus navularis 的金黄色葡萄球菌新家族生物膜破坏者

生物膜是微生物感染治疗中的一个关键挑战；例如，金黄色葡萄球菌通过在医疗器械上形成生物膜而引起慢性或致命感染。在此，发现真菌Arcopilus navularis产生一种新的PKS-NRPS代谢物家族，能够破坏金黄色葡萄球菌预先形成的生物膜。使用 HR-ESI-MS 和一维 (1D) 和二维 (2D) 核磁共振阐明了 Arcopilins A–F ( 1 – 6 )、特特拉姆酸和 arcopilin G ( 7 )（一种 2-吡啶酮）（核磁共振）光谱。它们的绝对构型是通过合成2的 MPTA-酯、分析¹ H– ¹ H 耦合常数和 ROESY 相关性以及与7的晶体结构进行比较来确定的。 Arcopilin A ( 1 ) 不仅能有效破坏金黄色葡萄球菌预先形成的生物膜，还能将庆大霉素和万古霉素的活性分别增强高达 115 倍和 31 倍。我们的研究结果表明，arcopilins 与无法破坏预先形成的生物膜的抗生素联合治疗金黄色葡萄球菌引起的感染具有潜在应用。

更新日期：2024-08-14

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