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With more than 200 bacterial and archaeal genomes completely sequenced, and more than 500 genomes at various stages of completion, we begin to appreciate the enormous diversity of prokaryotic genomes in terms of chromosomal structure, gene content and organization, and the abundance and fluidity of accessory and mobile genetic elements. The genome of a bacterial species is composed of conserved core genes and variable accessory genes. Mobile genetic elements, such as plasmids, transposons, insertion sequences, integrons, prophages, genomic islands, and pathogenicity islands, are part of the accessory genes, which can have a significant influence on the phenotype and biology of the organism. These mobile elements facilitate interspecies and intraspecies genetic exchange. They play an important role in the pathogenicity of bacteria, and are a major contributor to species diversity. Further genomic analysis will likely uncover more interesting genetic elements like small (noncoding) RNA genes that can play a significant role in gene regulation.

Perhaps the most significant benefit of microbial genomic sequences is the knowledge gained on the molecular process of genome evolution in microbes derived from comparative genomic analysis. Genetic variations are the driving forces of evolution. These are generated not only through base substitutions, small deletions and insertions, major DNA rearrangements and deletions, but also through DNA acquisition by horizontal gene transfer. Pathogens are evolved from diverse bacterial species. The molecular mechanisms involved are diverse, and likely affected by the conditions of the microenvironment inhabited by the evolving bacterial species.

Close to 100 genomes of bacterial pathogens have been sequenced, and yet most of the genomes sequenced have approx 25% of their open reading frames annotated as proteins with no known function. When genomic sequences of virulent and nonvirulent strains of a particular species are available, comparative genomic analysis is a powerful tool to identify putative virulence genes. Variation in virulence between strains of the same species is a common phenomenon. Availability of the genome sequence of a pathogen permits the application of DNA microarrays to investigate the genetic basis of this variation. DNA microarray technology has facilitated the identification of putative virulence determinants, host specificity genes, and bacterial and host genes that are activated or repressed during an infection. Isogenic mutants and suitable virulence assays are critical in verifying the role of the putative virulence genes identified.

In recent years, innate immunity has been one of the most intensively studied areas in immunology. It secures the first line of host defense against various microorganisms, including bacteria and viruses. Innate immune responses are highly conserved throughout evolution, and one important family of sensors responsible for initiating innate immune responses in mammals, the Toll-like receptors (TLRs), has recently been discovered. In this chapter, we will introduce the importance of innate immunity and TLR signals. We will then systematically discuss individual TLRs, their ligands, and the key downstream signaling molecules and pathways. Most of what we currently know is based on multidisciplinary approaches and supported by the phenotypes of specific knockout mice. Finally, we will briefly discuss the infectious diseases in humans that are caused by the mutations of TLR signals.

Genome sequencing of NCTC11168 identified an abundance of carbohydrate biosynthetic clusters comprising a large proportion of the genome. Many of these pathways were already under investigation including the lipooligosaccharide, flagellar O-linked protein glycosylation, and general N-linked protein glycosylation systems. Genome sequencing also identified a novel cluster of genes, which was subsequently shown to be involved in capsular polysaccharide biosynthesis. In order to fully understand the glycome, sophisticated analytical techniques were employed for functional characterization. We will describe these four important carbohydrate pathways highlighting the methods used to characterize these systems, the biological relevance the sugars play in campylobacter survival and pathogenesis, and the potential exploitation of the glycome for novel therapeutics against this common food-borne pathogen.

was the first bacterial species to have the genome of two independent strains completely sequenced. Infection with this pathogen, which may be the most frequent bacterial infection of humanity, causes peptic ulcer disease and gastric cancer. Other species are emerging as causes of infection, inflammation, and cancer in the intestine, liver, and biliary tract, although the true prevalence of these enterohepatic species in humans is not yet known. The murine pathogen Helicobacter hepaticus was the first enterohepatic species to have its genome completely sequenced. Here, we consider functional genomics of the genus , the comparative genomics of the genus Helicobacter, and the related genera Campylobacter and Wolinella.

The complete nucleotide sequences of three and, in the not too distant future, six strains from the genus will be available. Managing and maintaining these data will be a perpetual problem unless a system is devised to address this issue. We propose a central role for the International Union of Microbiological Societies Subcommittee on the Taxonomy of in maintaining and updating the annotated leptospiral genome sequences. The first step in this process is provided as part of this publication, namely a revision of the annotation of the three published genomes, and an internet location for the current versions of these genomes.

is a Gram-positive, intracellular bacterial pathogen responsible for severe food-borne illnesses resulting in central nervous system infection or abortion. induces its own internalization into mammalian cells, escapes from the host cell phagosome, replicates extensively in the cytosol, and spreads from one host cell to another through an F-actin-dependent motility process. Previously, classical genetic approaches were used to identify bacterial virulence factors critical for the intracellular life cycle of . The recent availability of the nucleotide sequence of L. monocytogenes has provided the potential for global analysis of bacterial proteins that affect pathogenesis. In this chapter, ways in which the genome has been used to probe the functions of bacterial proteins in virulence is discussed. At the end of the chapter, future genomic- or proteomic-based approaches that might improve or expand on current work are highlighted.

Tuberculosis (TB), caused by , remains a major cause of death around the world. Diseases caused by nontuberculous mycobacteria are increasingly associated with immunocompromised individuals. The availability of whole-genome sequences of mycobacterial species in the past several years has revolutionized TB research. This chapter provides an overview of the biology of mycobacteria and the diseases that they cause, with emphasis on how recent advances in genomics have improved our knowledge of the lifestyle and phylogeny of these organisms.

Mycoplasmas are cell wall-less bacterium with small genome sizes, typically 0.6-1.4 Mb. All mycoplasma species are obligate parasites with specific hosts. Their small genomes are thought to be the result of reductive evolution from an ancestor on a bacterial phylogenetic branch with a low guanine and cytosine content (i.e., a member of the Firmicutes, such as Clostridium spp. and Bacillus spp.) adapting to obligate parasitic life. In this chapter, the features of mycoplasma/ureaplasma/ phytoplasma genomes are discussed in terms of reductive evolution, a gene set for essential functions, and paralog formation under evolutionary pressure for gene reduction.