Bacterial Chemotaxis: Imagine If You Never Stopped Swimming

The study of chemotaxis of motile bacterial species certainly shows common themes. First, flagellar rotation propels the cells in an aqueous environment with random switches or stops in rotation. This switch or stop allows the cell to reorient resulting in a new swimming direction. Second, the “random walk” of swimming bacteria is biased. As cells near attractants, or molecules that are good for the cell, the rate of switching decreases due to more favorable conditions. Conversely, as cells near repellants, or molecules bad for the cell, the rate of switching increases as they search for a better niche. Many environmental cues have been shown to bias a bacterium's swimming direction including pH, temperature, gravity, light, oxygen, and numerous sources of carbon and nitrogen. Another theme conserved across Bacteria and Archaea is the cellular proteins necessary for chemotaxis and where these proteins localize within the cell, at the ends (or poles). The ultimate goal of sensing multiple environmental and cellular signals is to allow the cell to navigate to the most favorable niche. So, bacteria with dynamic metabolic strategies (nitrogen fixation, photosynthesis, anaerobiosis, etc.), due to the changing conditions within the niche they occupy (e.g. soil or aquatic), have larger repertoires of the genes necessary to survive.

Escherichia coli. The E. coli genome has one stretch of chemotaxis genes consisting of the necessary components for the signaling pathway. CheA (pronounced key-a) is a histidine kinase that associates with the methyl-accepting chemotaxis proteins (MCPs) via the adapter protein CheW. The MCPs, or chemoreceptors, in E. coli are embedded in the cell membrane and detect extracellular concentrations of attractants and repellants in the cell’s environment as it swims. Binding and dissociation of these molecules initiate the signal to CheA which activates one of two proteins, CheY and CheB. CheY-P (activated form) diffuses through the cell and binds the flagellar switch protein FliM, reversing the direction of flagella rotation from counter clockwise to clockwise. The signal output through CheY-P is terminated by another protein, CheZ. As part of the chemotaxis-specific adaptation system, activated CheB removes molecules from specific amino acid residues of MCPs which are added by the protein CheR. These molecular modifications of MCPs allow them to maintain greater sensitivity over a large concentration range of attractants or repellants.

Bacillus subtilis. The chemotaxis pathways of B. subtilis have become the best studied among Gram positive bacteria. When the MCPs bind a chemical attractant, CheA activates, starting the pathway activating CheY, which is opposite to the situation in E. coli, where active CheY is produced in response to an increase in repellent concentrations. Another major difference with chemotaxis in E. coli lies within the system that causes the pathway to adapt to constant concentrations of attractants or repellants. In E. coli, modified MCPs decrease CheA activity while the modifications in B. subtilis determines how the cell adapts. Adaptation in B. subtilis depends on CheB and CheR as well as proteins not encoded within E. coli.

• Rhodobacter sphaeroides is another well understood chemotaxis model system; however, it is an example of a more complex model. First, unlike E. coli, the genome of R. sphaeroides encodes multiple chemotaxis pathways. It also has two flagellar systems, Fla1 and Fla2, controlled by separate chemotaxis pathways.
• Myxococcus xanthus encodes 8 che operons, the most of any sequenced genome. M. xanthus also has two distinct motility systems; adventurous (A) and social (S) motility. S motility, motility of groups of cells, is necessary for aggregation into fruiting bodies while A motility is required for movement of individual cells using Type IV pili (TFP). The most studied pathway was discovered screening mutants that could not form fruiting bodies when nutrients were limiting. Closer analysis determined the mutations targeted the frz (“frizzy”) operon controlling cell reversals and sequence analysis revealed the gene products were homologous to che genes of enteric bacteria.
• Pseudomonas aeruginosa is another well studied organism for chemotaxis and chemotaxis-like systems. The P. aeruginosa PAO1 genome encodes four che-like signaling pathways as well as 26 chemoreceptors. One operon regulates pilus-mediated surface motility. Another system, the Wsp system, is involved in c-di-GMP regulated biofilm formation. The Wsp system is homologous to chemotaxis in E. coli with few modifications. The signal output of E. coli chemotaxis, phosphorylated CheY (a single domain protein), leads to a switch in flagella rotation while in P. aeruginosa, the signal output promotes production of c-di-GMP via WspR.
• Rhodospirillum centenum is a purple nonsulfur photosynthetic bacterium, predominantly aquatic, and capable of nitrogen fixation, or turning atmospheric nitrogen gas into a useful nitrogen source for the cell.

The number of receptor genes per genome also varies from 1 (Mezorhizobium loti) to 93 (putative, Pseudomonas syringae pv. oryzae str. 1_6) with no correlation between number of chemoreceptor genes and size of the genome. Lifestyle and environment of a bacterium, however, show strong correlation with the number of chemoreceptor its genome encodes. The sensing domain of chemoreceptors, usually found in the periplasm between inner and outer membranes, is highly variable with almost 9 out of 10 having no known sequence signature that offers clues to its function or what molecules it binds.

A recent study of Azospirillum brasilense Tlp1 (transducer-like protein 1) found this receptor to have two portions able to bind a sensed molecule, the sensory domain and a PilZ domain. Tlp1 was the first chemoreceptor studied with ability to sense the bacterial second messenger cyclic-di-GMP via the PilZ domain. Cyclic-di-GMP, only discovered in the late 1980s, is a molecule that is produced when environmental conditions of the cell require a transition in the cell's lifestyle, for example from free-swimming to life in a community biofilm. The presence of a PilZ domain on a chemoreceptor suggests that c-di-GMP (promotes biofilm production) sensed by a chemoreceptor (needed for free-swimming) could be a crossroad between multiple cellular pathways.

At the other end of this pathway, but just as important, is the flagellum. It consists of the rotary motor at the base in the inner membrane (Gram negative), a hook that allows the flagellum to extend away from the cell, and a long helical filament approximately 20 nanometers in diameter and roughly 500 nanometers in length. As a motor, the flagellum is very efficient and powerful at a speed between 200 and 1000 rpm and can switch direction instantaneously when active CheY binds.