Müsken Mathias, Klimmek Kathi, Sauer-Heilborn Annette, Donnert Monique, Sedlacek Ludwig, Suerbaum Sebastian, Häussler Susanne
Institute for Molecular Bacteriology, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
NPJ Biofilms Microbiomes. 2017 Sep 28;3:22. doi: 10.1038/s41522-017-0030-5. eCollection 2017.
Organized within biofilm communities, bacteria exhibit resistance towards a broad spectrum of antibiotics. Thus, one might argue that bacteria isolated from biofilm-associated chronic infections should be subjected to resistance profiling under biofilm growth conditions. Various test systems have been developed to determine the biofilm-associated resistance; however, it is not clear to what extent the in vitro results reflect the situation in vivo, and whether the biofilm-resistance profile should guide clinicians in their treatment choice. To address this issue, we used confocal microscopy in combination with live/dead staining, and profiled biofilm-associated resistance of a large number (>130) of clinical isolates from overall 15 cystic fibrosis patients. Our results demonstrate that in addition to a general non-responsiveness of bacteria when grown under biofilm conditions, there is an isolate-specific and antibiotic-specific biofilm-resistance profile. This individual resistance profile is independent on the structural properties of the biofilms. Furthermore, biofilm resistance is not linked to the resistance profile under planktonic growth conditions, or a mucoid, or small colony morphology of the tested isolates. Instead, it seems that individual biofilm structures evolve during biofilm-associated growth and are shaped by environment-specific cues. In conclusion, our results demonstrate that biofilm resistance profiles are isolate specific and cannot be deduced from commonly studied phenotypes. Further clinical studies will have to show the added value of biofilm-resistance profiling. Individualized diagnosis of biofilm resistance might lead to more rational recommendations for antimicrobial therapy and, thus, increased effectiveness of the treatment of chronically infected patients.
细菌在生物膜群落中组织起来，对抗广谱抗生素表现出抗性。因此，有人可能会认为，从生物膜相关慢性感染中分离出的细菌应在生物膜生长条件下进行抗性分析。已经开发了各种测试系统来确定与生物膜相关的抗性；然而，尚不清楚体外结果在多大程度上反映体内情况，以及生物膜抗性谱是否应指导临床医生进行治疗选择。为了解决这个问题，我们使用共聚焦显微镜结合活/死染色，对来自15名囊性纤维化患者的大量（>130）临床分离株的生物膜相关抗性进行了分析。我们的结果表明，除了细菌在生物膜条件下生长时普遍无反应外，还存在分离株特异性和抗生素特异性的生物膜抗性谱。这种个体抗性谱与生物膜的结构特性无关。此外，生物膜抗性与浮游生长条件下的抗性谱、测试分离株的黏液样或小菌落形态无关。相反，似乎个体生物膜结构在生物膜相关生长过程中演变，并由环境特异性线索塑造。总之，我们的结果表明生物膜抗性谱是分离株特异性的，不能从常见研究的表型中推断出来。进一步的临床研究将不得不证明生物膜抗性分析的附加价值。生物膜抗性的个体化诊断可能会导致对抗菌治疗更合理的建议，从而提高慢性感染患者治疗的有效性。
