Žiemytė Miglë, Rodríguez-Díaz Juan C, Ventero María P, Mira Alex, Ferrer María D
Genomics and Health Department, FISABIO Foundation, Valencia, Spain.
Servicio de Microbiología, Hospital General Universitario de Alicante, ISABIAL, Alicante, Spain.
Front Microbiol. 2020 Apr 17;11:553. doi: 10.3389/fmicb.2020.00553. eCollection 2020.
Microorganisms grown in biofilms are more resistant to antimicrobial treatment and immune system attacks compared to their planktonic forms. In fact, infections caused by biofilm-forming and are a large threat for public health, including patients with medical devices. The aim of the current manuscript was to test the effect of dalbavancin, a recently developed lipoglycopeptide antibiotic, alone or in combination with compounds contributing to bacterial cell disaggregation, on staphylococcal biofilm formation and elimination. We used real-time impedance measurements in microtiter plates to study biofilm growth dynamics of and strains, in the absence or presence of dalbavancin, linezolid, vancomycin, cloxacillin, and rifampicin. Further experiments were undertaken to check whether biofilm-detaching compounds such as -acetylcysteine (NAC) and ficin could enhance dalbavancin efficiency. Real-time dose-response experiments showed that dalbavancin is a highly effective antimicrobial, preventing staphylococcal biofilm formation at low concentrations. Minimum biofilm inhibitory concentrations were up to 22 higher compared to standard -test values. Dalbavancin was the only antimicrobial that could halt new biofilm formation on established biofilms compared to the other four antibiotics. The addition of NAC decreased dalbavancin efficacy while the combination of dalbavancin with ficin was more efficient than antibiotic alone in preventing growth once the biofilm was established. Results were confirmed by classical biofilm quantification methods such as crystal violet (CV) staining and viable colony counting. Thus, our data support the use of dalbavancin as a promising antimicrobial to treat biofilm-related infections. Our data also highlight that synergistic and antagonistic effects between antibiotics and biofilm-detaching compounds should be carefully tested in order to achieve an efficient treatment that could prevent both biofilm formation and disruption.
与浮游形式的微生物相比，生物膜中生长的微生物对抗菌治疗和免疫系统攻击更具抗性。事实上，由形成生物膜的微生物引起的感染对公众健康构成了巨大威胁，包括使用医疗设备的患者。本手稿的目的是测试最近开发的脂糖肽抗生素达巴万星单独使用或与有助于细菌细胞解聚的化合物联合使用对葡萄球菌生物膜形成和消除的影响。我们使用微量滴定板中的实时阻抗测量来研究金黄色葡萄球菌和表皮葡萄球菌菌株在有无达巴万星、利奈唑胺、万古霉素、氯唑西林和利福平情况下的生物膜生长动力学。还进行了进一步的实验，以检查生物膜分离化合物如N - 乙酰半胱氨酸（NAC）和无花果蛋白酶是否能提高达巴万星的效率。实时剂量反应实验表明，达巴万星是一种高效抗菌剂，在低浓度下可防止葡萄球菌生物膜形成。最低生物膜抑制浓度比标准MIC测试值高出多达22倍。与其他四种抗生素相比，达巴万星是唯一能阻止已形成生物膜上形成新生物膜的抗菌剂。添加NAC会降低达巴万星的疗效，而一旦生物膜形成，达巴万星与无花果蛋白酶联合使用在防止生长方面比单独使用抗生素更有效。结果通过经典的生物膜定量方法如结晶紫（CV）染色和活菌计数得到证实。因此，我们的数据支持将达巴万星用作治疗生物膜相关感染的有前景的抗菌剂。我们的数据还强调，为了实现既能预防生物膜形成又能破坏生物膜的有效治疗，应仔细测试抗生素与生物膜分离化合物之间的协同和拮抗作用。
