Symbiont Bacteria
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: Unraveling Outer Membrane Transport (Jul 2007)
Like all organisms, bacteria have to eat. However, bringing nutrients in from the outside world is not an easy task for many bacteria that are surrounded by an extra membrane. The second membrane, called the outer membrane, offers additional protection but at a cost: no energy can be generated or stored at the outer fringes of the cell. So, to import large, rare nutrients that cannot cross by diffusion alone, bacteria have evolved a unique transport system which couples the inner, energy-generating membrane to the passive outer membrane, known as the TonB-dependent transport system. TonB, an inner membrane-associated protein, transfers energy across the periplasm to a variety of outer-membrane transporters. These transporters have a large, beta-barrel structure which is blocked in the middle by a plug called the 'luminal domain'. How TonB transfers energy to the transporter and causes the luminal domain to come out is still a mystery though. Now with the help of computer simulations using NAMD and a recent crystal structure of TonB coupled to BtuB, the transporter responsible for vitamin B12 transport, researchers have shown that TonB can mechanically activate the transporter by pulling on the luminal domain, causing it to leave the barrel. Using steered molecular dynamics, it was found that TonB stayed firmly attached to the luminal domain of BtuB, even though the contact between the two is limited to just a handful of residues. Furthermore, this pulling initiated unfolding of the luminal domain, opening a transport pathway for the substrate. These results, the subject of a recent publication and also highlighted in Science, demonstrate how a mechanical coupling can bridge the gap between the two membranes, thus enabling outer membrane transport.
