Zhou Xuening, Wells Marilyn J, Gordon Vernita D
Center for Nonlinear Dynamics, The University of Texas at Austin, 2515 Speedway, Stop C1610, Austin, Texas 78712-11993, USA.
Interdisciplinary Life Sciences Graduate Program, Norman Hackerman Building, 100 East 24th St., NHB 4500, Austin, Texas 78712, USA.
bioRxiv. 2023 Oct 26:2023.10.25.564018. doi: 10.1101/2023.10.25.564018.
Biofilms are communities of microbes embedded in a matrix of extracellular polymeric substances (EPS). Matrix components can be produced by biofilm organisms and can also originate from the environment and then be incorporated into the biofilm. For example, we have recently shown that collagen, a host-produced protein that is abundant in many different infection sites, can be taken up into the biofilm matrix, altering biofilm mechanics. The biofilm matrix protects bacteria from clearance by the immune system, and some of that protection likely arises from the mechanical properties of the biofilm. and are common human pathogens notable for forming biofilm infections in anatomical sites rich in collagen. Here, we show that the incorporation of Type I collagen into and biofilms significantly hinders phagocytosis of biofilm bacteria by human neutrophils. However, enzymatic treatment with collagenase, which breaks down collagen, can partly or entirely negate the protective effect of collagen and restore the ability of neutrophils to engulf biofilm bacteria. From these findings, we suggest that enzymatic degradation of host materials may be a potential way to compromise biofilm infections and enhance the efficacy of the host immune response without promoting antibiotic resistance. Such an approach might be beneficial both in cases where the infecting species is known and also in cases wherein biofilm components are not readily known, such as multispecies infections or infections by unknown species.
生物膜是嵌入细胞外聚合物（EPS）基质中的微生物群落。基质成分可由生物膜中的微生物产生，也可源自环境，然后整合到生物膜中。例如，我们最近发现，胶原蛋白这种在许多不同感染部位大量存在的宿主产生的蛋白质，可被摄取到生物膜基质中，改变生物膜的力学性能。生物膜基质可保护细菌不被免疫系统清除，其中一些保护作用可能源于生物膜的机械性能。[具体细菌名称1]和[具体细菌名称2]是常见的人类病原体，以在富含胶原蛋白的解剖部位形成生物膜感染而闻名。在此，我们表明，将I型胶原蛋白整合到[具体细菌名称1]和[具体细菌名称2]生物膜中会显著阻碍人类中性粒细胞对生物膜细菌的吞噬作用。然而，用能分解胶原蛋白的胶原酶进行酶处理，可部分或完全消除胶原蛋白的保护作用，并恢复中性粒细胞吞噬生物膜细菌的能力。基于这些发现，我们认为对宿主物质进行酶降解可能是一种潜在的方法，既能损害生物膜感染，增强宿主免疫反应的功效，又不会促进抗生素耐药性。这种方法在已知感染物种的情况下以及生物膜成分不易确定的情况下，如多物种感染或未知物种感染，可能都有益处。
