Pathogenomics

Pathogen infections are among the leading causes of infirmity and mortality among humans and other animals in the world. Until recently, it has been difficult to compile information to understand the generation of pathogen virulence factors as well as pathogen behaviour in a host environment. The study of pathogenomics attempts to utilize genomic and metagenomics data gathered from high through-put technologies (e.g. sequencing or DNA microarrays), to understand microbe diversity and interaction as well as host-microbe interactions involved in disease states. The bulk of pathogenomics research concerns itself with pathogens that affect human health; however, studies also exist for plant and animal infecting microbes. Pathogen infections are among the leading causes of infirmity and mortality among humans and other animals in the world. Until recently, it has been difficult to compile information to understand the generation of pathogen virulence factors as well as pathogen behaviour in a host environment. The study of pathogenomics attempts to utilize genomic and metagenomics data gathered from high through-put technologies (e.g. sequencing or DNA microarrays), to understand microbe diversity and interaction as well as host-microbe interactions involved in disease states. The bulk of pathogenomics research concerns itself with pathogens that affect human health; however, studies also exist for plant and animal infecting microbes. In the early investigation of microbial genomics, it was difficult and costly to obtain sequence information for any pathogen. In 1995, the first pathogen genome, that of Haemophilus influenza, was sequenced by traditional Sanger methods. Sanger methods, however, were slow and costly. The emergence of second-generation high-throughput sequencing technologies has allowed for microbial sequence information to be obtained much more quickly and at a considerably lower cost. Largely thanks to second-generation sequencing methods, tens of thousands of pathogen genomes have been sequenced since 1995. The emergence of second-generation high-throughput sequencing technologies has allowed for microbial sequence information to be obtained much more quickly and at a considerably lower cost. This influx of information is also due to the capacity of sequencing platforms to generate the sequences of many organisms in parallel. With the sequences of many organisms available for analysis, scientists, through their investigations, began to challenge some of the earlier tenets of bacterial genome structure. Older paradigms of microbial genomics believed that only a few strains were sufficient to represent a specific bacterial species. It was thought that bacterial genomes, like eukaryotes, were relatively stable. In 2001, however, the sequences of Escherichia coli 0157:H7 was obtained in a study by Perna and her colleagues; the study showed that two members of the same bacterial species can differ as much as 30% in genomic content. It became evident that sequencing multiple strains for a species, rather than a few selectively chosen ones, was necessary to understand the diversity in a microbial species gene pool. It was also increasingly important to understand how to account for these differences in genomic content across a species strains and how it may contribute to pathogenic behaviour or prevent the formation of pathogens. More recently, the sequenced genomic data have been catalogued in databases and made publicly available online (there also exist non-publicly available databases in the private sector). The availability and influx of this information presses upon those who conduct pathogenomics research to come up with a way of drawing meaningful conclusions from these data. In addition, the availability of such data on the Internet encourages global collaboration of labs. Pathogens may be prokaryotic (archaea or bacteria), single-celled Eukarya or viruses. Prokaryotic genomes have typically been easier to sequence due to smaller genome size compared to Eukarya. Due to this, there is a bias in reporting pathogenic bacterial behaviour. More recently there have been increased efforts to sequence Eukarya genomes and more will be underway in the future. Regardless of this bias in reporting, many of the dynamic genomic events are similar across all the types of pathogen organisms. Pathogenomics does not focus exclusively on understanding pathogen-host interactions. Insight of individual or cooperative pathogen behaviour provides knowledge into the development or inheritance of pathogen virulence factors. Through a deeper understanding of the small subunits that cause infection, it may be able possible to develop novel therapeutics that are efficient and cost effective. Dynamic genomes with high plasticity are necessary to allow pathogens, especially bacteria, to survive in changing environments. With the assistance of high throughput sequencing methods and in silico technologies, it is possible to detect, compare and catalogue many of these dynamic genomic events. Particular interest is in understanding how genomic events lead to pathogen development and how these events may be interrupted to prevent it. Three forces act in shaping the pathogen genome: gene gain, gene loss, and genome rearrangement. The knowledge and detection of these genomic dynamic events are necessary in the construction of useful therapeutic tools to combat pathogens.