School of Mechanical Engineering, Faculty of Engineering, Macquarie University, Sydney, Australia.
Woolcock Institute of Medical Research, Sydney, Australia.
Biotechnol Bioeng. 2022 Jun;119(6):1483-1497. doi: 10.1002/bit.28077. Epub 2022 Mar 21.
Biofilms are communities of bacterial cells encased in a self-produced polymeric matrix and exhibit high tolerance towards environmental stress. Despite the plethora of research on biofilms, most biofilm models are produced using mono-interface culture in static flow conditions, and knowledge of the effects of interfaces and mechanical forces on biofilm development remains fragmentary. This study elucidated the effects of air-liquid (ALI) or liquid-liquid (LLI) interfaces and mechanical shear forces induced by airflow and hydrodynamic flow on biofilm growing using a custom-designed dual-channel microfluidic platform. Results from this study showed that comparing biofilms developed under continuous nutrient supply and shear stresses free condition to those developed with limited nutrient supply, ALI biofilms were four times thicker, 60% less permeable, and 100 times more resistant to antibiotics, while LLI biofilms were two times thicker, 20% less permeable, and 100 times more resistant to antibiotics. Subjecting the biofilms to mechanical shear stresses affected the biofilm structure across the biofilm thickness significantly, resulting in generally thinner and denser biofilm compared to their controlled biofilm cultured in the absence of shear stresses, and the ALI and LLI biofilm's morphology was vastly different. Biofilms developed under hydrodynamic shear stress also showed increased antibiotic resistance. These findings highlight the importance of investigating biofilm growth and its mechanisms in realistic environmental conditions and demonstrate a feasible approach to undertake this study using a novel platform.
生物膜是由细菌细胞组成的群落,被自身产生的聚合物基质包裹,并表现出对环境压力的高耐受性。尽管对生物膜进行了大量的研究,但大多数生物膜模型都是在静态流动条件下使用单界面培养产生的,而关于界面和机械力对生物膜发展的影响的知识仍然是零散的。本研究使用定制的双通道微流控平台阐明了气液(ALI)或液液(LLI)界面以及气流和流体动力流引起的机械剪切力对生物膜生长的影响。本研究的结果表明,与在连续营养供应和无剪切应力条件下生长的生物膜相比,在有限营养供应下生长的生物膜的厚度增加了四倍,渗透率降低了 60%,对抗生素的抵抗力提高了 100 倍,而 LLI 生物膜的厚度增加了两倍,渗透率降低了 20%,对抗生素的抵抗力提高了 100 倍。使生物膜承受机械剪切力会显著影响整个生物膜厚度的生物膜结构,导致与在不存在剪切力的情况下培养的对照生物膜相比,通常更薄且更密集,并且 ALI 和 LLI 生物膜的形态有很大差异。在流体动力剪切应力下发育的生物膜也表现出增加的抗生素抗性。这些发现强调了在实际环境条件下研究生物膜生长及其机制的重要性,并展示了使用新型平台进行这项研究的可行方法。