▪ Abstract Most prokaryotic signal-transduction systems and a few eukaryotic pathways use phosphotransfer schemes involving two conserved components, a histidine protein kinase and a response regul...

Two-component signal transduction

We explain the biology and physics underlying the chemotactic (foraging) behavior of E. coli bacteria. We explain a variety of bacterial swarming and social foraging behaviors and discuss the control system on the E. coli that dictates how foraging should proceed. Next, a computer program that emulates the distributed optimization process represented by the activity of social bacterial foraging is presented. To illustrate its operation, we apply it to a simple multiple-extremum function minimization problem and briefly discuss its relationship to some existing optimization algorithms. The article closes with a brief discussion on the potential uses of biomimicry of social foraging to develop adaptive controllers and cooperative control strategies for autonomous vehicles. For this, we provide some basic ideas and invite the reader to explore the concepts further.

Biomimicry of bacterial foraging for distributed optimization and control

A major portion of the toxicity of hydrogen peroxide in Escherichia coli is attributed to DNA damage mediated by a Fenton reaction that generates active forms of hydroxyl radicals from hydrogen peroxide, DNA-bound iron, and a constant source of reducing equivalents. Kinetic peculiarities of DNA damage production by hydrogen peroxide in vivo can be reproduced by including DNA in an in vitro Fenton reaction system in which iron catalyzes the univalent reduction of hydrogen peroxide by the reduced form of nicotinamide adenine dinucleotide (NADH). To minimize the toxicity of oxygen radicals, the cell utilizes scavengers of these radicals and DNA repair enzymes. On the basis of observations with the model system, it is proposed that the cell may also decrease such toxicity by diminishing available NAD(P)H and by utilizing oxygen itself to scavenge active free radicals into superoxide, which is then destroyed by superoxide dismutase.

https://science.sciencemag.org/content/sci/240/4857/1302.full.pdf

DNA damage and oxygen radical toxicity

Protein phosphorylation and regulation of adaptive responses in bacteria.

PAS domains are newly recognized signaling domains that are widely distributed in proteins from members of the Archaea and Bacteria and from fungi, plants, insects, and vertebrates. They function as input modules in proteins that sense oxygen, redox potential, light, and some other stimuli. Specificity in sensing arises, in part, from different cofactors that may be associated with the PAS fold. Transduction of redox signals may be a common mechanistic theme in many different PAS domains. PAS proteins are always located intracellularly but may monitor the external as well as the internal environment. One way in which prokaryotic PAS proteins sense the environment is by detecting changes in the electron transport system. This serves as an early warning system for any reduction in cellular energy levels. Human PAS proteins include hypoxia-inducible factors and voltage-sensitive ion channels; other PAS proteins are integral components of circadian clocks. Although PAS domains were only recently identified, the signaling functions with which they are associated have long been recognized as fundamental properties of living cells.

PAS Domains: Internal Sensors of Oxygen, Redox Potential, and Light

Contrary to the prevalent view, there seems to be no competition in the mammalian female genital tract among large numbers of sperm cells that are racing towards the egg. Instead, small numbers of the ejaculated sperm cells enter the Fallopian tube, and these few must be guided to make the remaining long, obstructed way to the egg. Here, we review the mechanisms by which mammalian sperm cells are guided to the egg.

https://www.royanaward.com/files13/Royan%20Award%20-%20Giojalas%20-%20pdf%20paper%201.pdf

Sperm guidance in mammals - an unpaved road to the egg.

Regulation of the direction of flagellar rotation is central to the mechanism of bacterial chemotaxis. The transitions between counterclockwise and clockwise rotation are controlled by a "switch complex" composed of three proteins (FliG, FliM, and FliN) and located at the base of the flagellar motor. The mechanism of function of the switch is unknown. Here we demonstrate that the diffusible clockwise-signal molecule, the CheY protein, binds to the switch, that the primary docking site is FliM, that the extent of CheY binding to FliM is dependent upon the phosphorylation level of CheY, and that it is unaffected by the other two switch proteins. This study provides a biochemical demonstration of binding of a signal molecule to the bacterial switch and demonstrates directly that phosphorylation regulates the activity of this molecule.

https://www.pnas.org/content/pnas/90/19/8787.full.pdf

Phosphorylation-dependent binding of a signal molecule to the flagellar switch of bacteria.

Chemotaxis is a mechanism by which bacteria efficiently and rapidly respond to changes in the chemical composition of their environment, approaching chemically favorable environments and avoiding unfavorable ones. This behavior is achieved by integrating signals received from receptors that sense the environment and modulating the direction of flagellar rotation accordingly (for reviews, see references 39, 43, and 100). Early studies in the modern era, initiated some 4 decades ago (1), uncovered the behavioral response of cells to changes in the chemical composition of their environment and the correlation between flagellar rotation and the swimming mode of the cells. They also identified most of the gene products involved in chemotaxis (for reviews, see references 50 and 56). The mode of signal transduction began to be understood only in the mid-1980s, when the possibilities of electrical signaling and a direct interaction between the receptors and flagella were eliminated (for a review, see reference 41). The possibility of indirect interaction between the receptors and flagella via a protein that is activated by the receptors and inactivated as it diffuses through the cytoplasm was then raised (96). Subsequently, sequential transient phosphorylation of chemotaxis proteins was found to be a key process in signal transduction (for a review, see reference 25). During the last decade, it was established that the signal in bacteria such as Escherichia coli and Salmonella enterica serovar Typhimurium is transduced via protein-protein interactions. These interactions have been extensively studied, contributing greatly to the elucidation of the chemotaxis-signaling cascade. The chemotactic response in bacteria such as E. coli and Salmonella serovar Typhimurium is accomplished by signal transmission between two supramolecular complexes—the receptor complexes, located mainly at the pole(s) of the cell, and the flagellar-motor complexes (usually 5 to 10 complexes per cell), randomly distributed around the cell and embedded within the cell membrane. A messenger protein, CheY, shuttles back and forth between the complexes and transduces the signal from the receptors to the flagella (Fig. 1). The interaction of this messenger protein with the flagellar-motor supramolecular complex increases the probability of shifting the direction of flagellar rotation from the default direction, counterclockwise (CCW), to clockwise (CW) (for a review see reference 38). The consequence of CW rotation is an abrupt turning motion (tumbling), after which (when the default direction resumes) the cell swims in a new direction. Here we review the protein-protein interactions involved in chemotactic signaling, including interactions within the supramolecular complexes, interactions between the complexes and the messenger protein CheY, and interactions between CheY and the proteins that regulate its signaling state. Interactions involved in the signaling pathway leading to adaptation will also be reviewed. We will mainly focus on functional aspects of the interactions. The reader is referred to references 13, 35, 43, 54, and 81 for more-detailed structural aspects. Because this is a minireview, the reference list is incomplete. Whenever possible, reference is made to reviews or papers that provide access to the original literature.

How signals are heard during bacterial chemotaxis: protein-protein interactions in sensory signal propagation.

Acetyl coenzyme A synthetase (Acs) activates acetate to acetyl coenzyme A through an acetyladenylate intermediate; two other enzymes, acetate kinase (Ack) and phosphotransacetylase (Pta), activate acetate through an acetyl phosphate intermediate We subcloned acs, the Escherichia coli open reading frame purported to encode Acs (F R Blattner, V Burland, G Plunkett III, H J Sofia, and D L Daniels, Nucleic Acids Res 21:5408-5417, 1993) We constructed a mutant allele, delta acs::Km, with the central 072-kb BclI-BclI portion of acs deleted, and recombined it into the chromosome Whereas wild-type cells grew well on acetate across a wide range of concentrations (25 to 50 mM), those deleted for acs grew poorly on low concentrations ( or = 25 mM), and those deleted for acs, ackA, and pta did not grow on acetate at any concentration tested Expression of acs from a multicopy plasmid restored growth to cells deleted for all three genes Relative to wild-type cells, those deleted for acs did not activate acetate as well, those deleted for ackA and pta displayed even less activity, and those deleted for all three genes did not activate acetate at any concentration tested Induction of acs resulted in expression of a 72-kDa protein, as predicted by the reported sequence This protein immunoreacted with antiserum raised against purified Acs isolated from an unrelated species, Methanothrix soehngenii The purified E coli Acs then was used to raise anti-E coli Acs antiserum, which immunoreacted with a 72-kDa protein expressed by wild-type cells but not by those deleted for acs When purified in the presence, but not in the absence, of coenzyme A, the E coli enzyme activated acetate across a wide range of concentrations in a coenzyme A-dependent manner On the basis of these and other observations, we conclude that this open reading frame encodes the acetate-activating enzyme, Acs

Cloning, characterization, and functional expression of acs, the gene which encodes acetyl coenzyme A synthetase in Escherichia coli.

In humans, only a small fraction (2-12%) of a sperm population can respond by chemoattraction to follicular factors. This recent finding led to the hypothesis that chemotaxis provides a mechanism for selective recruitment of functionally mature spermatozoa (i.e., of capacitated spermatozoa, which possess the potential to undergo the acrosome reaction and fertilize the egg). This study aimed to examine this possibility. Capacitated spermatozoa were identified by their ability to undergo the acrosome reaction upon stimulation with phorbol 12-myristate 13-acetate. Under capacitating conditions, only a small portion (2-14%) of the spermatozoa were found to be capacitated. The spermatozoa were then separated according to their chemotactic activity, which resulted in a subpopulation enriched with chemotactically responsive spermatozoa and a subpopulation depleted of such spermatozoa. The level of capacitated spermatozoa in the former was approximately 13-fold higher than that in the latter. The capacitated state was temporary (50 min < life span < 240 min), and it was synchronous with the chemotactic activity. A continuous process of replacement of capacitated/chemotactic spermatozoa within a sperm population was observed. Spermatozoa that had stopped being capacitated did not become capacitated again, which indicates that the capacitated state is acquired only once in a sperm's lifetime. A total sperm population depleted of capacitated spermatozoa stopped being chemotactic. When capacitated spermatozoa reappeared, chemotactic activity was restored. These observations suggest that spermatozoa acquire their chemotactic responsiveness as part of the capacitation process and lose this responsiveness when the capacitated state is terminated. We suggest that the role of sperm chemotaxis in sperm-egg interaction in vivo may indeed be selective recruitment of capacitated spermatozoa for fertilizing the egg.

https://www.pnas.org/content/pnas/92/24/11039.full.pdf

Michael Eisenbach

Papers

Sperm guidance in mammals - an unpaved road to the egg.

Phosphorylation-dependent binding of a signal molecule to the flagellar switch of bacteria.

How signals are heard during bacterial chemotaxis: protein-protein interactions in sensory signal propagation.

Cloning, characterization, and functional expression of acs, the gene which encodes acetyl coenzyme A synthetase in Escherichia coli.

Sperm capacitation in humans is transient and correlates with chemotactic responsiveness to follicular factors.