Role of Multicellular Aggregates in Biofilm Formation.
Role of Multicellular Aggregates in Biofilm Formation.
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DOI：
10.1128/mbio.00237-16
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发表时间：
2016-03-22
期刊：
影响因子：
6.4
通讯作者：
Bjarnsholt T
中科院分区：
文献类型：
--
作者：
Kragh KN;Hutchison JB;Melaugh G;Rodesney C;Roberts AE;Irie Y;Jensen PØ;Diggle SP;Allen RJ;Gordon V;Bjarnsholt T
在传统的体外生物膜发育模型中，单个细菌细胞在表面播种，繁殖，并成熟成多细胞的三维结构。许多研究都致力于阐明控制单细胞与表面初始附着的机制。然而，在自然环境和感染过程中，细菌细胞倾向于聚集成多细胞聚集体，生物膜也可以在扩散过程中脱落聚集体。这使得生物膜可能经常由聚集体和单细胞播种，但这些聚集体如何影响生物膜的形成和发育尚不清楚。在这里，我们使用实验和计算相结合的方法来确定在铜绿假单胞菌生物膜的早期发育过程中单细胞和预形成的聚集体的相对适合度。我们发现聚集体的相对适合度明显取决于周围单细胞的密度，即对生长资源的竞争水平。当聚集体和单个细胞之间的竞争较低时，聚集体具有生长劣势，因为聚集体内部难以获得生长资源。然而，如果竞争激烈，聚集体表现出更高的适应性，因为垂直延伸到表面以上的聚集体顶部的细胞可以更好地获得生长资源。聚集体播种的其他优势，如更早地转变为生物膜样表型，增强对抗生素和免疫反应的恢复能力，可能会增加这种生态效益。我们的研究结果表明，目前的生物膜形成模型应该被重新考虑，以纳入聚集物在生物膜形成中的作用。在过去的几十年里，关于生物膜的发展模式已经达成了共识，包括单个浮游细菌细胞附着在表面和随后成熟生物膜的发展。这项研究提出的结果要求对这个严格的模型进行修改。我们展示了当生物膜附着在表面时，自由漂浮的生物膜聚集体如何对生物膜的发展产生深远的局部影响。我们的研究结果表明，降落在表面上的聚集体最终将胜过附着在聚集体周围的单细胞产生的生物膜群体，并主导当地生物膜的发展。这些结果表明，在获取营养物质方面，预先形成的生物膜聚集体可能比浮游细胞具有适应性优势。我们的发现增加了越来越突出的理解，即生物膜生活方式是细菌的默认状态，浮游单细胞可能最多只是一种过渡状态。
In traditional models of in vitro biofilm development, individual bacterial cells seed a surface, multiply, and mature into multicellular, three-dimensional structures. Much research has been devoted to elucidating the mechanisms governing the initial attachment of single cells to surfaces. However, in natural environments and during infection, bacterial cells tend to clump as multicellular aggregates, and biofilms can also slough off aggregates as a part of the dispersal process. This makes it likely that biofilms are often seeded by aggregates and single cells, yet how these aggregates impact biofilm initiation and development is not known. Here we use a combination of experimental and computational approaches to determine the relative fitness of single cells and preformed aggregates during early development of Pseudomonas aeruginosa biofilms. We find that the relative fitness of aggregates depends markedly on the density of surrounding single cells, i.e., the level of competition for growth resources. When competition between aggregates and single cells is low, an aggregate has a growth disadvantage because the aggregate interior has poor access to growth resources. However, if competition is high, aggregates exhibit higher fitness, because extending vertically above the surface gives cells at the top of aggregates better access to growth resources. Other advantages of seeding by aggregates, such as earlier switching to a biofilm-like phenotype and enhanced resilience toward antibiotics and immune response, may add to this ecological benefit. Our findings suggest that current models of biofilm formation should be reconsidered to incorporate the role of aggregates in biofilm initiation. During the past decades, there has been a consensus around the model of development of a biofilm, involving attachment of single planktonic bacterial cells to a surface and the subsequent development of a mature biofilm. This study presents results that call for a modification of this rigorous model. We show how free floating biofilm aggregates can have a profound local effect on biofilm development when attaching to a surface. Our findings show that an aggregate landing on a surface will eventually outcompete the biofilm population arising from single cells attached around the aggregate and dominate the local biofilm development. These results point to a regime where preformed biofilm aggregates may have a fitness advantage over planktonic cells when it comes to accessing nutrients. Our findings add to the increasingly prominent comprehension that biofilm lifestyle is the default for bacteria and that planktonic single cells may be only a transition state at the most.