Schilcher Katrin, Andreoni Federica, Dengler Haunreiter Vanina, Seidl Kati, Hasse Barbara, Zinkernagel Annelies S
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Antimicrob Agents Chemother. 2016 Sep 23;60(10):5957-67. doi: 10.1128/AAC.00463-16. Print 2016 Oct.
Staphylococcus aureus biofilms are extremely difficult to treat. They provide a protected niche for the bacteria, rendering them highly recalcitrant toward host defenses as well as antibiotic treatment. Bacteria within a biofilm are shielded from the immune system by the formation of an extracellular polymeric matrix, composed of polysaccharides, extracellular DNA (eDNA), and proteins. Many antibiotics do not readily penetrate biofilms, resulting in the presence of subinhibitory concentrations of antibiotics. Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections.
金黄色葡萄球菌生物被膜极难治疗。它们为细菌提供了一个受保护的微环境，使细菌对宿主防御以及抗生素治疗具有高度抗性。生物被膜内的细菌通过由多糖、细胞外DNA（eDNA）和蛋白质组成的细胞外聚合物基质的形成而免受免疫系统的影响。许多抗生素不易穿透生物被膜，导致存在亚抑制浓度的抗生素。在这里，我们表明亚抑制浓度的克林霉素通过替代σ因子B（σ(B)）在金黄色葡萄球菌中引发转录应激反应，并上调了主要生物被膜相关基因atlA、lrgA、agrA、psm基因、fnbA和fnbB的表达。我们的数据表明，亚抑制浓度的克林霉素改变了金黄色葡萄球菌形成生物被膜的能力，并使生物被膜基质的组成向更高的eDNA含量转变。了解对亚抑制浓度的临床相关抗生素（如克林霉素）作出反应的生物被膜组装和分散的分子机制，对于进一步优化与生物被膜相关的金黄色葡萄球菌感染的抗生素治疗策略至关重要。
