Bacterial communities within the human body greatly influence human health and play a significant role in diseas e predisposition, pathogenic, physical fitness, and dietary responsiveness. Importantly, bacteria utilize highly co operative macromolecular machines to accomplish many cellular functions. Here we seek to understand, with molecular and atomistic fidelity, two such machines: the cellulosome and the chemosensory array, which underlie the phenomen a of bacterial plant fiber degradation and chemotaxis respectively.
Biofuels: Bacteria can make a living off a very wide range of food sources. This agnosticism enables them to, among other things, serve as essential symbionts in animal digestive tracts where they assist their hosts in d egrading cellulose fibers into metabolizable compounds. In particular, bacteria in the rumen of the cow face an esp ecially tough job (see Tight Job in the Gut), digesting the hardy cellulose fibers of grasses. Key to their task are molecular tentacles on the cell s urface of certain gut bacteria, so-called cellulosomes (pictured right), which develop a tight grasp on cellulose a nd then effectively cleave the molecules. In general, human gut bacteria (and their role in the broader human micro biome) are one of the most intensely researched topics in medicine.
Bacterial Chemotaxis: Bacteria monitor their environments and respond by way of a fundamental sensory cap ability known as chemotaxis---one of the best studied behavioral systems in biology. Chemotactic responses in bacte ria involve large complexes of sensory proteins, known as chemosensory arrays, that process the information obtaine d from the bacteria's habitat to determine its swimming pattern. In this sense, the chemosensory array functions as a bacterial brain, transforming sensory input into motile output. Despite great strides in the understanding of ho w the chemosensory array's constituent proteins fit and work together, a high-resolution description has, until rec ently, remained elusive (see Computing the Bacterial Brain). Here we are combining computational and experimental techniques to explore in detail the molecular mechanisms underlying sensory signal transduction and amplification within this amazing biological appar atus.
Spotlight: Computing the Bacterial Brain (Mar 2016)
made with VMD
Motile bacteria position themselves within their habitats optimally, seeking proximity to favorable growth conditions while avoiding unfavorable ones. Cues used for this placement come in the form of small chemicals, so-called attractors and repellants, as well as physical factors such as favorable visible light and unfavorable UV radiation. To balance such a broad range of factors, bacteria monitor their environments and respond by way of a fundamental sensory capability known as chemotaxis. Chemotactic responses in bacteria involve large complexes of sensory proteins, known as chemosensory arrays, that process the information obtained from the bacteria's habitat to determine its swimming pattern. In this sense, the chemosensory array functions as a bacterial brain, transforming sensory input into motile output. Despite great strides in the understanding of how the chemosensory array's constituent proteins fit and work together, a high-resolution description of the kind needed to explore in detail the molecular mechanisms underlying sensory signal transduction within the array has remained elusive. A new study, utilizing cryo-electron microscopy and molecular dynamics simulations with NAMD, reports the highest resolution images yet of the bacterial brain's molecular anatomy. Using computational techniques, structural data from X-ray crystallography and electron microscopy are compared to derive an atomically resolved model of the chemosensory array's extended molecular structure that involves millions of atoms. Subsequent simulations of the model revealed a novel conformational change in a key sensory protein, that is interpreted as a key signaling event in the translation of chemosensory information into swimming pattern. More details on this work can be found in a recent news release as well as on our bacterial chemotaxis website.