Hsu Chi-Yu, Lin Mei-Hui, Chen Chien-Cheng, Chien Shih-Chin, Cheng Yi-Hsiang, Su I-Ning, Shu Jwu-Ching
Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan.
FEMS Immunol Med Microbiol. 2011 Nov;63(2):236-47. doi: 10.1111/j.1574-695X.2011.00846.x.
Staphylococcus aureus, an important human pathogen, is particularly adept at producing biofilms on implanted medical devices. Although antibiotic treatment of nonsusceptible bacteria will not kill these strains, the consequences should be studied. The present study focuses on investigating the effect of vancomycin on biofilm formation by vancomycin-non-susceptible S. aureus. Biofilm adherence assays and scanning electron microscopy demonstrated that biofilm formation was significantly enhanced following vancomycin treatment. Bacterial autolysis of some subpopulations was observed and was confirmed by the live/dead staining and confocal laser scanning microscopy. A significant increase in polysaccharide intercellular adhesin (PIA) production was observed by measuring icaA transcript levels and in a semi-quantitative PIA assay in one resistant strain. We show that the release of extracellular DNA (eDNA) via cidA-mediated autolysis is a major contributor to vancomycin-enhanced biofilm formation. The addition of xenogeneic DNA could also significantly enhance biofilm formation by a PIA-overproducing S. aureus strain. The magnitude of the development of the biofilm depends on a balance between the amounts of eDNA and PIA. In conclusion, sublethal doses of cell wall-active antibiotics like vancomycin induce biofilm formation through an autolysis-dependent mechanism in vancomycin-non-susceptible S. aureus.
金黄色葡萄球菌是一种重要的人类病原体，特别擅长在植入式医疗设备上形成生物膜。虽然对不敏感细菌进行抗生素治疗不会杀死这些菌株，但仍应研究其后果。本研究重点调查万古霉素对万古霉素不敏感金黄色葡萄球菌生物膜形成的影响。生物膜黏附试验和扫描电子显微镜表明，万古霉素治疗后生物膜形成显著增强。观察到一些亚群的细菌自溶，并通过活/死染色和共聚焦激光扫描显微镜得到证实。通过测量icaA转录水平和在一株耐药菌株中进行半定量PIA测定，观察到多糖细胞间黏附素（PIA）产量显著增加。我们表明，通过cidA介导的自溶释放细胞外DNA（eDNA）是万古霉素增强生物膜形成的主要原因。添加异种DNA也可显著增强PIA高产金黄色葡萄球菌菌株的生物膜形成。生物膜形成的程度取决于eDNA和PIA量之间的平衡。总之，亚致死剂量的细胞壁活性抗生素如万古霉素通过自溶依赖性机制在万古霉素不敏感金黄色葡萄球菌中诱导生物膜形成。
