Planktonic Aggregates of Staphylococcus aureus Protect against Common Antibiotics

Bacterial cells are mostly studied during planktonic growth although in their natural habitats they are often found in communities such as biofilms with dramatically different physiological properties. We have examined another type of community namely cellular aggregates observed in strains of the human pathogen Staphylococcus aureus. By laser-diffraction particle–size analysis (LDA) we show, for strains forming visible aggregates, that the aggregation starts already in the early exponential growth phase and proceeds until post-exponential phase where more than 90% of the population is part of the aggregate community. Similar to some types of biofilm, the structural component of S. aureus aggregates is the polysaccharide intercellular adhesin (PIA). Importantly, PIA production correlates with the level of aggregation whether altered through mutations or exposure to sub-inhibitory concentrations of selected antibiotics. While some properties of aggregates resemble those of biofilms including increased mutation frequency and survival during antibiotic treatment, aggregated cells displayed higher metabolic activity than planktonic cells or cells in biofilm. Thus, our data indicate that the properties of cells in aggregates differ in some aspects from those in biofilms. It is generally accepted that the biofilm life style protects pathogens against antibiotics and the hostile environment of the host. We speculate that in aggregate communities S. aureus increases its tolerance to hazardous environments and that the combination of a biofilm-like environment with mobility has substantial practical and clinical importance.尽管细菌在自然生境中多以群落形式存在，比如具有显著不同生理特性的生物被膜（biofilm），但学界对细菌的研究大多集中于浮游生长状态。本研究聚焦于另一类细菌群落——即人类病原菌金黄色葡萄球菌（Staphylococcus aureus）菌株中观察到的细胞聚集体。通过激光衍射粒径分析（laser-diffraction particle–size analysis，简称LDA），我们针对可形成可见聚集体的菌株展开研究，结果显示聚集体形成始于指数生长早期，并持续至指数生长后期，此时超过90%的菌体均属于聚集体群落。与部分类型的生物被膜类似，金黄色葡萄球菌聚集体的结构组分为细胞间多糖粘附素（polysaccharide intercellular adhesin，简称PIA）。值得注意的是，无论通过基因突变或是暴露于选定抗生素的亚抑菌浓度环境，细胞间多糖粘附素的表达量均与聚集体形成水平呈正相关。尽管聚集体的部分特性与生物被膜相似，比如突变频率升高、抗生素处理下存活率提升，但聚集体菌体的代谢活性要高于浮游菌体或生物被膜内的菌体。因此，本研究数据表明，聚集体内菌体的特性在部分方面与生物被膜内菌体存在差异。目前学界普遍认为，生物被膜生活方式可帮助病原菌抵御抗生素及宿主内的恶劣环境。我们推测，在聚集体群落中，金黄色葡萄球菌可提升其对危险环境的耐受性，而兼具类生物被膜环境与移动性的特性，具有重要的实际应用与临床价值。