Kovach Kristin N, Fleming Derek, Wells Marilyn J, Rumbaugh Kendra P, Gordon Vernita Diane
Department of Physics and Center for Nonlinear Dynamics , The University of Texas at Austin , Austin , Texas 78712 , United States.
Department of Surgery , Texas Tech University Health Sciences Center , Lubbock , Texas 79430 , United States.
Langmuir. 2020 Feb 18;36(6):1585-1595. doi: 10.1021/acs.langmuir.9b02188. Epub 2020 Feb 7.
Biofilms are communities of bacteria embedded in a polymeric matrix which are found in infections and in environments outside the body. Breaking down the matrix renders biofilms more susceptible to physical disruption and to treatments such as antibiotics. Different species of bacteria, and different strains within the same species, produce different types of matrix polymers. This suggests that targeting specific polymers for disruption may be more effective than nonspecific approaches to disrupting biofilm matrixes. In this study, we treated biofilms with enzymes that are specific to different matrix polymers. We measured the resulting alteration in biofilm mechanics using bulk rheology and changes in structure using electron microscopy. We find that, for biofilms grown in vitro, the effect of enzymatic treatment is greatest when the enzyme is specific to a dominant matrix polymer. Specifically matched enzymatic treatment tends to reduce yield strain and yield stress and increase the rate of biofilm drying, due to increased diffusivity as a result of network compromise. Electron micrographs qualitatively suggest that well-matched enzymatic treatments reduce long-range structure and shorten connecting network fibers. Previous work has shown that generic glycoside hydrolases can cause dispersal of bacteria from in vivo and ex vivo biofilms into a free-swimming state, and thereby make antibiotic treatment more effective. For biofilms grown in wounded mice, we find that well-matched treatments that result in the greatest mechanical compromise in vitro induce the least dispersal ex vivo. Moreover, we find that generic glycoside hydrolases have no measurable effect on the mechanics of biofilms grown in vitro, while previous work has shown them to be highly effective at inducing dispersal in vivo and ex vivo. This highlights the possibility that effective approaches to eradicating biofilms may depend strongly on the growth environment.
生物膜是嵌入聚合物基质中的细菌群落，存在于感染部位和体外环境中。分解基质会使生物膜更容易受到物理破坏以及抗生素等治疗手段的影响。不同种类的细菌以及同一物种内的不同菌株会产生不同类型的基质聚合物。这表明针对特定聚合物进行破坏可能比非特异性破坏生物膜基质的方法更有效。在本研究中，我们用对不同基质聚合物具有特异性的酶处理生物膜。我们使用整体流变学测量生物膜力学的变化，并使用电子显微镜观察结构变化。我们发现，对于体外培养的生物膜，当酶对主要的基质聚合物具有特异性时，酶处理的效果最佳。由于网络受损导致扩散性增加，特异性匹配的酶处理往往会降低屈服应变和屈服应力，并提高生物膜干燥速率。电子显微镜照片定性地表明，匹配良好的酶处理会减少长程结构并缩短连接网络纤维。先前的研究表明，通用糖苷水解酶可导致细菌从体内和体外生物膜中分散成自由游动状态，从而使抗生素治疗更有效。对于在受伤小鼠体内生长的生物膜，我们发现体外导致最大机械损伤的匹配良好的处理在体外诱导的分散最少。此外，我们发现通用糖苷水解酶对体外培养的生物膜力学没有可测量的影响，而先前的研究表明它们在体内和体外诱导分散方面非常有效。这突出了根除生物膜的有效方法可能强烈依赖于生长环境的可能性。
