细胞外 DNA 在达巴万星治疗皮肤和软组织感染耐甲氧西林金黄色葡萄球菌（MRSA）生物膜中的作用。

Methicillin-resistant Staphylococcus aureus (MRSA) has become the leading cause of skin and soft tissue infections (SSTIs). Biofilm production further complicates patient treatment, contributing to increased bacterial persistence and antibiotic tolerance. The study aimed to explore the efficacy of different antibiotics on biofilm-producing MRSA isolated from patients with SSTI. A total of 32 MRSA strains were collected from patients with SSTI. The MIC and minimal biofilm eradication concentration (MBEC) were measured in planktonic and biofilm growth. The study showed that dalbavancin, linezolid, and vancomycin all inhibited MRSA growth at their EUCAST susceptible breakpoint. Of the MRSA strains, 87.5% ( = 28) were strong biofilm producers (SBPs), while only 12.5% ( = 4) were weak biofilm producers (WBPs). The MBEC values for dalbavancin were significantly lower than those of linezolid and vancomycin in all tested strains. We also found that extracellular DNA (eDNA) contributes to the initial microbial attachment and biofilm formation. The amount of eDNA differed among MRSA strains and was significantly higher in those isolates with high dalbavancin and vancomycin tolerance. Exogenously added DNA increased the MBEC and protection of biofilm cells from dalbavancin activity. Of note, the relative abundance of eDNA was higher in MRSA biofilms exposed to MBEC dalbavancin than in untreated MRSA biofilms and those exposed to sub-MIC. Overall, dalbavancin was the most active antibiotic against MRSA biofilms at concentrations achievable in the human serum. Moreover, the evidence of a drug-related increase of eDNA and its contribution to antimicrobial drug tolerance reveals novel potential targets for antibiofilm strategies against MRSA. Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs) worldwide. In addition, methicillin-resistant S. aureus (MRSA) is increasingly frequent in postoperative infections and responsible for a large number of hospital readmissions and deaths. Biofilm formation by S. aureus is a primary risk factor in SSTIs, due to a higher antibiotic tolerance. Our study showed that the biofilm-forming capacity varied among MRSA strains, although strong biofilm producers were significantly more abundant than weak biofilm producer strains. Notably, dalbavancin demonstrated a potent antibiofilm activity at concentrations achievable in human serum. Nevertheless, dalbavancin activity was affected by an increased concentration of extracellular DNA in the biofilm matrix. This study provides novel insight for designing more targeted therapeutic strategies against MRSA and to prevent or eradicate harmful biofilms.

耐甲氧西林金黄色葡萄球菌（MRSA）已成为皮肤和软组织感染（SSTIs）的主要原因。生物膜的产生进一步使患者的治疗复杂化，导致细菌持续存在和抗生素耐药性增加。本研究旨在探讨不同抗生素对从 SSTI 患者中分离出的产生物膜的 MRSA 的疗效。从 SSTI 患者中收集了 32 株 MRSA 菌株。在浮游和生物膜生长中测量 MIC 和最小生物膜清除浓度（MBEC）。研究表明，达巴万星、利奈唑胺和万古霉素均在其 EUCAST 敏感折点抑制 MRSA 生长。在所测试的菌株中，87.5%（=28）为强生物膜产生菌（SBPs），而只有 12.5%（=4）为弱生物膜产生菌（WBPs）。达巴万星的 MBEC 值明显低于所有测试菌株中利奈唑胺和万古霉素的 MBEC 值。我们还发现，细胞外 DNA（eDNA）有助于初始微生物附着和生物膜形成。MRSA 菌株之间的 eDNA 量不同，并且在那些对达巴万星和万古霉素具有高耐受性的分离株中明显更高。外源性添加 DNA 会增加 MBEC 并保护生物膜细胞免受达巴万星活性的影响。值得注意的是，与未经处理的 MRSA 生物膜和低于 MIC 的 MRSA 生物膜相比，暴露于 MBEC 达巴万星的 MRSA 生物膜中 eDNA 的相对丰度更高。总体而言，达巴万星在可达到人血清浓度下对 MRSA 生物膜最有效。此外，药物相关的 eDNA 增加及其对抗菌药物耐药性的贡献揭示了针对 MRSA 的抗生物膜策略的新潜在靶点。

金黄色葡萄球菌是全球皮肤和软组织感染（SSTIs）最常见的原因。此外，耐甲氧西林金黄色葡萄球菌（MRSA）在术后感染中越来越常见，是大量医院再次入院和死亡的原因。金黄色葡萄球菌的生物膜形成是 SSTIs 的主要危险因素，因为抗生素耐药性更高。我们的研究表明，尽管强生物膜产生菌的丰度明显高于弱生物膜产生菌，但 MRSA 菌株的生物膜形成能力存在差异。值得注意的是，达巴万星在可达到人血清浓度下表现出强大的抗生物膜活性。然而，达巴万星的活性受到生物膜基质中细胞外 DNA 浓度增加的影响。本研究为设计针对 MRSA 的更有针对性的治疗策略以及预防或根除有害生物膜提供了新的见解。