Systems Biology Of Microbial Infection

The systems biology of microbial infections aims at describing and analysing the confrontation of the host with bacterial and fungal pathogens. It intends to understand and to model the interaction of the host, in particular the immune system of humans or animals, with components of pathogens. This comprises experimental studies that provide spatio-temporal data from monitoring the response of host and pathogenic cells to perturbations or when interacting with each other, as well as the integrative analysis of genome-wide data from both the host and the pathogen. In perspective, the host-pathogen interaction should be described by a combination of spatio-temporal models with interacting molecular networks of the host and the pathogen. The aim is to unravel the main mechanisms of pathogenicity, to identify diagnostic biomarkers and potential drug targets, and to explore novel strategies for personalized therapy by computer simulations. Some microorganisms are part of the normal microbial flora, existing either in a mutualistic or commensal relationship with the host. Microorganisms become pathogenic if they posses certain physiological characteristics and virulence determinants as well as capabilities for immune evasion. Despite the different pathogenesis of infections, there are several common traits: (1) Before infection, pathogens must be able to overcome (epithelial) barriers. The infection starts by adhesion and colonization and is followed by entering of the pathogen into the host through the mucosa or (injured) skin. (2) Next, infection arises if the pathogen multiplies and overgrows the normal microbial flora, either at the place of entrance or in deeper tissue layers or organs. (3) After the growth phase, the pathogen damages the host’s cells, tissues and organs by producing toxins or destructive enzymes. Thus, systems biology of microbial infection comprises all levels of the pathogen and the host’s immune system. The investigation may start with the pathogen, its adhesion and colonization at the host, its interaction with host cell types e.g. epithelia cells, dendritic cells, macrophages, neutrophils, natural killer cells, etc. Because infection diseases are mainly found in patients with a weakened immune system, e.g. reduced activities of immune effector cells or defects in the epithelial barriers, systems biology of infection can also start with modelling of the immune defence including innate and adaptive immunity. Systems biological studies comprise both experimental and theoretical approaches. The experimental studies may be dedicated to reveal the relevance of certain genes or proteins in the above mentioned processes on the side of the pathogen and/or the host by applying functional and biochemical analyses based on knock-out mutants and knock- down experiments. At the theoretical, i.e. mathematical and computational, side systems biology of microbial infection comprises: (1) modelling of molecular mechanisms of bacterial or fungal infections, (2) modelling of non-protective and protective immune defences against microbial pathogens to generate information for possible immune therapy approaches, (3) modelling of infection dynamics and identification of biomarkers for diagnosis and for individualized therapy, (4) identifying essential virulence determinants and thereby predicting potential drug targets.

Systems biology is the study of the dynamic interactions of more than one component in a biological system in order to understand and predict the behavior of the system as a whole. Systems biology is a rapidly expanding discipline fuelled by the 'omics' era and new technological advances that have increased the precision of data. A focus on simple single cell organisms, such as bacteria, aids tractability and means that systems microbiology is a rapidly maturing science. Recommended for all microbiology laboratories, this book contains cutting-edge reviews by world-leading experts on the systems biology of microorganisms. As well as covering theoretical approaches and mathematical modeling, the book includes case studies on single microbial species of bacteria and archaea, and it explores the systems analysis of microbial phenomena, such as chemotaxis and phagocytosis. The topics covered include: the mathematical models for systems biology * systems biology of Escherichia coli metabolism * bacterial chemotaxis * systems biology of infection * host-microbe interactions * phagocytosis * system-level study of metabolism in Mycobacterium tuberculosis * systems biology of Sulfolobus.

First, systems biology is an inter-disciplinary approach, requiring the combined talents of biologists, mathematicians, and computer scientists. Second, systems biology is holistic, with the goal of obtaining a comprehensive understanding of the workings of biological systems. This is achieved through the acquisition of massive amounts of data by high-throughput technologies—oligonucleotide microarrays, mass spectrometry, and next-generation sequencing—and the analysis of this data through sophisticated mathematical algorithms. It is perhaps the use of mathematics, to integrate abundant and diverse types of data and to generate models of interconnected molecular networks, that best characterizes systems biology.

Many potential applications of synthetic and systems biology are relevant to the challenges associated with the detection, surveillance, and responses to emerging and re-emerging infectious diseases. On March 14 and 15, 2011, the Institute of Medicine's (IOM's) Forum on Microbial Threats convened a public workshop in Washington, DC, to explore the current state of the science of synthetic biology, including its dependency on systems biology; discussed the different approaches that scientists are taking to engineer, or reengineer, biological systems; and discussed how the tools and approaches of synthetic and systems biology were being applied to mitigate the risks associated with emerging infectious diseases. The Science and Applications of Synthetic and Systems Biology is organized into sections as a topic-by-topic distillation of the presentations and discussions that took place at the workshop. Its purpose is to present information from relevant experience, to delineate a range of pivotal issues and their respective challenges, and to offer differing perspectives on the topic as discussed and described by the workshop participants. This report also includes a collection of individually authored papers and commentary.

This comprehensive volume focuses on molecular methods and principles of prokaryotic and eukaryotic pathogens. The authors present the molecular and cellular aspects by focusing on the interactions between pathogenic microorganisms and their hosts. The publication begins with an overview of the most important and dangerous causative agents of infectious diseases. Next are discussions of how microbial "weapons," pathogenicity factors, protein secretion machines, and surface variation systems work, presenting the molecular and genetic methods that are used by scientists for their discovery and analysis. Furthermore, infectious diseases are discussed in light of the newly formed research areas of evolutionary and cellular microbiology and genomics. Future aspects on diagnostic techniques, therapy, and vaccine development are also presented.

This book brings together the various fields of functional genomics and systems biology that provide information on metabolic function. There is special emphasis on the identification of drug targets. The book includes practical examples from the various "omic" sciences as well as theoretical examples of how integrated knowledge of these sciences can be applied to drug discovery. It is of interest to researchers in the pharmaceutical drug discovery environment.