Summarizes the science and recent research developments of chemical communication among bacteria

Quorum sensing (QS) describes a chemical communication behavior that is nearly universal among bacteria. Individual cells release a diffusible small molecule (an autoinducer) into their environment. A high concentration of this autoinducer serves as a signal of high population density, triggering new patterns of gene expression throughout the population. However QS is often much more complex than this simple census-taking behavior. Many QS bacteria produce and detect multiple autoinducers, which generate quorum signal cross talk with each other and with other bacterial species. QS gene regulatory networks respond to a range of physiological and environmental inputs in addition to autoinducer signals. While a host of individual QS systems have been characterized in great molecular and chemical detail, quorum communication raises many fundamental quantitative problems which are increasingly attracting the attention of physical scientists and mathematicians. Key questions include: What kinds of information can a bacterium gather about its environment through QS? What physical principles ultimately constrain the efficacy of diffusion-based communication? How do QS regulatory networks maximize information throughput while minimizing undesirable noise and cross talk? How does QS function in complex, spatially structured environments such as biofilms? Previous books and reviews have focused on the microbiology and biochemistry of QS. With contributions by leading scientists and mathematicians working in the field of physical biology, this volume examines the interplay of diffusion and signaling, collective and coupled dynamics of gene regulation, and spatiotemporal QS phenomena. Chapters will describe experimental studies of QS in natural and engineered or microfabricated bacterial environments, as well as modeling of QS on length scales spanning from the molecular to macroscopic. The book aims to educate physical scientists and quantitative-oriented biologists on the application of physics-based experiment and analysis, together with appropriate modeling, in the understanding and interpretation of the pervasive phenomenon of microbial quorum communication.

Microbial extracellular polymeric substances (EPS) are the key components for the aggregation of microorganisms in biofilms, flocs and sludge. They are composed of polysaccharides, proteins, nucleic acids, lipids and other biological macromolecules. EPS provide a highly hydrated gel matrix in which microbial cells can establish stable synergistic consortia. Cohesion and adhesion as well as morphology, structure, biological function and other properties such as mechanical stability, diffusion, sorption and optical properties of microbial aggregates are determined by the EPS matrix. Also, the protection of biofilm organisms against biocides is attributed to the EPS. Their matrix allows phase separation in biofiltration and is also important for the degradation of particulate material which is of great importance for the self purification processes in surface waters and for waste water treatment.

Over the past 40 years, quorum sensing (QS)-a type of chemical communication used by common bacteria-has been shown to be play an increasingly important role in bacterial communities. QS mediates a wide array of bacterial group behaviors such as initiating infection, mediating symbiosis, and adapting to environmental stimuli. A common QS pathway used by many Gram-positive bacteria is the accessory gene regulator (agr) system, which has been recognized as a key regulator of virulence in several clinically relevant pathogens. Activation of agr QS and its downstream regulation is dependent upon the production and reception of a peptide signal known as the autoinducing peptide (AIP). Interfering with this signaling process using non-native chemical modulators that target the various components of agr represents an approach to attenuate agr QS activity and alter associated bacterial phenotypes. There currently is a dearth of potent and efficacious chemical modulators for the majority of agr systems. Moreover, many of these synthetic ligands have been only examined in vitro, and many questions remain about the modes by which bacteria use agr QS in vivo and the methods by which to best leverage these chemical modulators to reduce bacterial virulence. In this thesis, I describe my work to create, develop, and apply chemical tools to investigate agr QS in three important pathogens. I performed structure-activity relationship (SAR) analyses on the native AIP signal of Listeria monocytogenes and uncovered the most potent agr agonists and antagonists of its agr system to date. These modulators can strongly promote or inhibit biofilm formation, a critical virulence phenotype in L. monocytogenes, demonstrating the utility of chemical control of agr activity. Structural and SAR studies of the AIPs from Staphylococcus epidermidis revealed new structural insights into modulator potency and efficacy, as well as enabling the development of the first agonists capable of activating multiple AgrC receptors. Lastly, I characterized degradable polymeric materials loaded with potent Staphylococcus aureus agr antagonists and demonstrated their ability to attenuate infection in a murine model. The studies presented herein represent significant advances towards developing chemical tools to probe and control agr QS in important Gram-positive bacteria.

Intraspecific communication involves the activation of chemoreceptors and subsequent activation of different central areas that coordinate the responses of the entire organism—ranging from behavioral modification to modulation of hormones release. Animals emit intraspecific chemical signals, often referred to as pheromones, to advertise their presence to members of the same species and to regulate interactions aimed at establishing and regulating social and reproductive bonds. In the last two decades, scientists have developed a greater understanding of the neural processing of these chemical signals. Neurobiology of Chemical Communication explores the role of the chemical senses in mediating intraspecific communication. Providing an up-to-date outline of the most recent advances in the field, it presents data from laboratory and wild species, ranging from invertebrates to vertebrates, from insects to humans. The book examines the structure, anatomy, electrophysiology, and molecular biology of pheromones. It discusses how chemical signals work on different mammalian and non-mammalian species and includes chapters on insects, Drosophila, honey bees, amphibians, mice, tigers, and cattle. It also explores the controversial topic of human pheromones. An essential reference for students and researchers in the field of pheromones, this is also an ideal resource for those working on behavioral phenotyping of animal models and persons interested in the biology/ecology of wild and domestic species.

Providing a comprehensive insight into cellular signaling processes in bacteria with a special focus on biotechnological implications, this is the first book to cover intercellular as well as intracellular signaling and its relevance for biofilm formation, host pathogen interactions, symbiotic relationships, and photo- and chemotaxis. In addition, it deals in detail with principal bacterial signaling mechanisms -- making this a valuable resource for all advanced students in microbiology. Dr. Krämer is a world-renowned expert in intracellular signaling and its implications for biotechnology processes, while Dr. Jung is an expert on intercellular signaling and its relevance for biomedicine and agriculture.

Cell-cell communication in bacteria involves the production, release, and subsequent detection of chemical signaling molecules called autoinducers. This process, called quorum sensing, allows bacteria to regulate gene expression on a population-wide scale. Processes controlled by quorum sensing are usually ones that are unproductive when undertaken by an individual bacterium but become effective when undertaken by the group. For example, quorum sensing controls bioluminescence, secretion of virulence factors, biofilm formation, sporulation, and the exchange of DNA. Thus, quorum sensing is a mechanism that allows bacteria to function as multi-cellular organisms. Bacteria make, detect, and integrate information from multiple autoinducers, some of which are used exclusively for intra-species communication while others enable communication between species. Research is now focused on the development of therapies that interfere with quorum sensing to control bacterial virulence.