The molecular microbiology and physics of bacterial flotation

一些水生细菌可以制造细胞内腔（完全由蛋白质组成），这种腔只对环境气体渗透。这种结构被称为气体囊泡（GVs），它们形成聚集体（气体液泡），通过相衬显微镜可以识别。制造gv的水生细菌可能利用它们产生浮力现象，允许在静态水柱中向上漂浮。这种能力对一些光合细菌（如蓝藻）是有用的，它们需要在分层的水生生态位中上升，以获得特定波长的光，或在气液界面获取营养物质或氧气，或者可能逃避捕食者或竞争对手。gv通常由一个主要蛋白（GvpA）和一个次要蛋白（GvpC）组成，并形成具有顶极的圆柱形结构。我们最近在肠杆菌，沙雷氏菌（与大肠杆菌“相关”）的ATCC39006菌株中发现了气体囊泡。在这个菌株中存在gv是一个独特的，完全出乎意料的观察结果。除了生产GV细胞器和漂浮能力外，该菌株还有其他有趣的特性。它生产两种抗生素。一种抗生素是抗菌的（碳青霉烯类），另一种（芥子菌素）可以杀死原生动物和其他微生物。ATCC39006可以通过鞭毛游动（运动），可以在固体表面聚集并产生表面清洁剂分子（生物表面活性剂），从而使新的生态位或宿主表面扩散和定植。该菌株还通过分泌植物细胞壁降解酶来腐烂植物（马铃薯），并杀死微小的蠕虫（秀丽隐杆线虫），因此它也是杀线虫的。我们在菌株ATCC39006中鉴定了19个GV基因簇，并设计了表达沙雷氏菌GV基因的大肠杆菌菌株，使大肠杆菌在静态培养中漂浮到气液界面。在沙雷氏菌中，gv的产生依赖于细菌细胞的密度，这一过程被称为“群体感应”，由细胞间移动的扩散化学信号控制。信号分子对沙雷氏菌gv的产生至关重要；群体感应突变体不会漂浮。因此，在这种细菌中，细胞间的化学信号控制着胞内细胞器的发育，因此化学通讯信号也是一种形态因子。群体感应还控制了该菌株中抗生素的生产，因此这些有毒分子在gv组装的同时产生。我们发现GV的产生也受到氧气限制的上调，这意味着GV可能允许浮选到液体表面以获取氧气。我们与剑桥大学应用数学和理论物理系（DAMTP）的雷蒙德·戈尔茨坦教授合作，一直在研究这种细菌的浮力现象。基于我们对这种细菌流动性的遗传学、生理学和物理学的了解，我们已经提出了一个可测试的工作假设，关于为什么GV的产生和浮选受到群体感应控制；对氧气水平有反应，在发育上倾向于鞭毛运动。我们的模型还预测了为什么这两种抗生素的生产已经演变成与gv和浮选的发展同时发生。我们现在将研究细菌细胞密度，运动性，生物对流，GV发展，浮力和抗生素生产之间的迷人联系。这项研究具有广泛的影响。它影响了微生物对环境压力线索的生态适应；细菌细胞间化学通讯；细菌细胞器形态发生；以及微生物冲突和生态位防御的适应度值。我们对其中一些生物过程的进化的理解将通过对描述其行为的基本数学物理的欣赏而得到显著增强；一个令人兴奋的跨学科研究，微生物学与数学！

Some aquatic bacteria can make intracellular chambers (made entirely of protein) that are permeable only to environmental gasses. The structures are called gas vesicles (GVs) and they form conglomerates (gas vacuoles) identifiable by phase contrast microscopy. The aquatic bacteria that make GVs may use them for the phenomenon of buoyancy, allowing upward flotation in a static water column. This ability can be useful for some photosynthetic bacteria (e.g. cyanobacteria) that need to rise in a stratified aquatic niche to access light of a specific wavelength, or to acquire nutrients or oxygen at the air-liquid interface, or perhaps to escape predators or competitors. The GVs usually comprise a major protein (GvpA) and a minor protein (GvpC) and form cylindrical structures with apical poles. We recently discovered gas vesicles in strain ATCC39006 of the enterobacterium, Serratia ("related" to E. coli). The existence of GVs in this strain was a unique, and totally unexpected, observation. In addition to production of GV organelles and the capacity to float, this strain has other interesting traits. It makes two antibiotics. One antibiotic is antibacterial (a carbapenem) and another (prodigiosin) can kill protozoans and other microbes. ATCC39006 can swim via flagella (motility) and can swarm on solid surfaces and make surface detergent molecules (biosurfactants) enabling spreading and colonisation of new niches or host surfaces. The strain also rots plants (potato) by secreting plant cell wall degrading enzymes and it kills microscopic worms (Caenorhabditis elegans) and so it is also nematicidal. We identified the cluster of 19 GV genes in strain ATCC39006 and we engineered E. coli strains that expressed the Serratia GV genes and allowed E. coli to float up to the air-liquid interface in static culture. Production of the GVs in Serratia was bacterial cell density-dependent in a process called "Quorum Sensing" controlled by a diffusible chemical signal that moves between cells. The signalling molecule is essential for production of the GVs in Serratia; quorum-sensing mutants don't float. Therefore, in this bacterium, an intercellular chemical signal controls the development of intracellular organelles and thus the chemical communication signal is also a morphogen. Quorum sensing also controls the production of the antibiotics in this strain and so these toxic molecules are made at the same time as the GVs are assembled. We showed that GV production was also up-regulated by oxygen limitation, implying that GVs may allow flotation to the liquid surface to acquire oxygen. In collaboration with Professor Raymond Goldstein in the Department of Applied Mathematics and Theoretical Physics (DAMTP) in Cambridge, we have been investigating the phenomenon of buoyancy in this bacterium. Based on our knowledge of the genetics, physiology and physics of mobility in this bacterium we have developed a testable working hypothesis as to why GV production, and flotation, is under quorum sensing control; responsive to oxygen levels, and developmentally preferred to flagellar motility. Our model also predicts why the production of the two antibiotics has evolved to be co-incident with the development of the GVs, and flotation. We will now investigate the fascinating connections between bacterial cell population density, motility, bioconvection, GV development, buoyancy and antibiotic production. This study has wide ramifications. It impinges on areas such as ecological adaptation to environmental stress cues in microbes; intercellular chemical communication in bacteria; bacterial organelle morphogenesis; and the fitness value of microbial conflict and niche defence. Our understanding of the evolution of some of these biological processes will be significantly enhanced by an appreciation of the underlying mathematical physics that describes their behaviour; an exciting interdisciplinary study where microbiology meets mathematics!