The Epsilonproteobacteria is the fifth validly described class of the phylum Proteobacteria, known primarily for clinical relevance and for chemolithotrophy in various terrestrial and marine environments, including deep-sea hydrothermal vents. As 16S rRNA gene repositories have expanded and protein marker analysis become more common, the phylogenetic placement of this class has become less certain. A number of recent analyses of the bacterial tree of life using both 16S rRNA and concatenated marker gene analyses have failed to recover the Epsilonproteobacteria as monophyletic with all other classes of Proteobacteria. In order to address this issue, we investigated the phylogenetic placement of this class in the bacterial domain using 16S and 23S rRNA genes, as well as 120 single-copy marker proteins. Single- and concatenated-marker trees were created using a data set of 4,170 bacterial representatives, including 98 Epsilonproteobacteria. Phylogenies were inferred under a variety of tree building methods, with sequential jackknifing of outgroup phyla to ensure robustness of phylogenetic affiliations under differing combinations of bacterial genomes. Based on the assessment of nearly 300 phylogenetic tree topologies, we conclude that the continued inclusion of Epsilonproteobacteria within the Proteobacteria is not warranted, and that this group should be reassigned to a novel phylum for which we propose the name Epsilonbacteraeota (phyl. nov.). We further recommend the reclassification of the order Desulfurellales (Deltaproteobacteria) to a novel class within this phylum and a number of subordinate changes to ensure consistency with the genome-based phylogeny. Phylogenomic analysis of 658 genomes belonging to the newly proposed Epsilonbacteraeota suggests that the ancestor of this phylum was an autotrophic, motile, thermophilic chemolithotroph that likely assimilated nitrogen from ammonium taken up from the environment or generated from environmental nitrate and nitrite by employing a variety of functional redox modules. The emergence of chemoorganoheterotrophic lifestyles in several Epsilonbacteraeota families is the result of multiple independent losses of various ancestral chemolithoautotrophic pathways. Our proposed reclassification of this group resolves an important anomaly in bacterial systematics and ensures that the taxonomy of Proteobacteria remains robust, specifically as genome-based taxonomies become more common.

Metabolic pathways have traditionally been described in terms of biochemical reactions and metabolites. Using structural genomics and systems biology, we generated a three-dimensional reconstruction of the central metabolic network of the bacterium, Thermotoga maritima (TM). The network encompassed 478 proteins of which 120 were determined by experiment and 358 were modeled. Structural analysis revealed that proteins forming the network are dominated by a small number (only 182) of basic shapes (folds) performing diverse, but mostly related functions. Most of these folds are already present in the essential core (~30%) of the network, and its expansion by nonessential proteins is achieved with relatively few additional folds. Thus, integration of structural data with networks analysis generates insight into the function, mechanism and evolution of biological networks.

Beyond the well-known role of proteolytic machinery in protein degradation and turnover, many specialized proteases play a key role in various regulatory processes. Thousands of highly specific proteolytic events are associated with normal and pathological conditions, including bacterial and viral infections. However, the information about individual proteolytic events is dispersed over multiple publications and is not easily available for large-scale analysis. CutDB is one of the first systematic efforts to build an easily accessible collection of documented proteolytic events for natural proteins in vivo or in vitro. A CutDB entry is defined by a unique combination of these three attributes: protease, protein substrate and cleavage site. Currently, CutDB integrates 3070 proteolytic events for 470 different proteases captured from public archives (such as MEROPS and HPRD) and publications. CutDB supports various types of data searches and displays, including clickable network diagrams. Most importantly, CutDB is a community annotation resource based on a Wikipedia approach, providing a convenient user interface to input new data online. A recent contribution of 568 proteolytic events by several experts in the field of matrix metallopeptidases suggests that this approach will significantly accelerate the development of CutDB content. CutDB is publicly available at .

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