Introduction In Our Hands

During the last 20 years the growing field of genome research has provided pivotal insights into the molecular mechanisms of bacterial infections and the evolution of pathogenicity of bacterial microorganisms. Specific virulence traits have been characterized in different bacterial species at the genome level. A majority of these genes have been shown to be encoded by genetic elements which are expected to be horizontally transferred, e.g., bacteriophages, plasmids, and genomic islands [1, 2] leading to a mosaic genome structure in bacterial pathogens. By defining the blueprint of pathogenicity at the genomic scale, the former differentiation of chromosomal (genome) and episomal factors (plasmid) has been expanded in terms of a "core genome" and a "flexible gene pool." The first encompasses the genomic backbone that determines the metabolic functions of the bacteria. The latter encodes the pathogenic and fitness functions that enable the bacteria to exert their virulence properties in contact with host cells, finally leading to cell damage and disease.

Before the genomic era only a few virulence genes were known in pathogenic species, leading to a merely fragmentary picture of the interaction of bacteria with the host. The determination of whole-genome sequences of pathogenic bacteria and the comparison of genome sequences from pathogenic and closely related nonpathogenic species revealed a much more detailed picture of bacterial virulence or even invalidated previous concepts. On the other hand, however, the enormous amount of data collected in genome research often clouds the issue. Even in bacterial species such as E. coli, which has been investigated for several decades, pathogenomic studies provide novel insights [3, 4], revealing a rather complex pattern of virulence factors with a genomic patchwork of chromosomal virulence determinants in the instance of extraintestinal pathogenic E. coli (ExPEC) [5, 6].

The same is true for the genomic structure of antibiotic resistance determinants, which basically undergo a comparable distribution among bacteria using a very similar mechanism of horizontal spreading [7, 8]. The emergence of antibiotic resistance and multidrug resistance in bacterial pathogens underscores the need for the development of novel classes of antibiotics. The availability of complete genome sequence data from many important human pathogens has already provided a wealth of fundamental information from which to identify potential molecular targets for drug discovery. Determining the presence or absence of certain pathogenicity islands or genomic islands harboring multiple antibiotic resistance genes in bacterial isolates may further aid in identifying the cause of a disease, estimating its pathogenic potential, and predicting its antibiotic resistance. Thus, pathogenomic research has contributed to microbial diagnostics, pathotyp-ing of bacteria, and the detection of novel target structures for the therapy and prevention of microbial infections.

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