Pathogenomics

During the earlier times when genomics was being studied, scientists found it challenging to sequence genetic information. The field began to explode in 1977 when Fred Sanger, PhD, along with his colleagues, sequenced the DNA-based genome of a bacteriophage, using a method now known as the Sanger Method. The Sanger Method for sequencing DNA exponentially advanced molecular biology and directly led to the ability to sequence genomes of other organisms, including the complete human genome. With the ability to rapidly sequence DNA, new insights developed, such as the discovery that since prokaryotic genomes are more diverse than originally thought, it is necessary to sequence multiple strains in a species rather than only a few. E.coli was an example of why this is important, with genes encoding virulence factors in two strains of the species differing by at least thirty percent. Such knowledge, along with more thorough study of genome gain, loss, and change, is giving researchers valuable insight into how pathogens interact in host environments and how they are able to infect hosts and cause disease. == Pathogen Bioinformatics ==

With this high influx of new information, there has arisen a higher demand for bioinformatics so scientists can properly analyze the new data. In response, software and other tools have been developed for this purpose. Also, as of 2008, the amount of stored sequences was doubling every 18 months, making urgent the need for better ways to organize data and aid research. In response, many publicly accessible databases and other resources have been created, including the NCBI pathogen detection program, the Pathosystems Resource Integration Centre (PATRIC), Pathogenwatch, the Virulence Factor Database (VFDB) of pathogenic bacteria, Until 2022, the most sequenced pathogens are Salmonella enterica and E. coli - Shigella. The sequencing technologies, the bioinformatics tools, the databases, statistics related to pathogen genomes and the applications in forensics, epidemiology, clinical practice and food safety have been extensively reviewed. == Microbe analysis ==

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 behavior. Regardless of this bias in reporting, many of the dynamic genomic events are similar across all the types of pathogen organisms. Genomic evolution occurs via gene gain, gene loss, and genome rearrangement, and these "events" are observed in multiple pathogen genomes, with some bacterial pathogens experiencing all three. Cause and analysis of genomic diversity Dynamic genomes with high plasticity are necessary to allow pathogens, especially bacteria, to survive in changing environments. There is a need to analyze more than a single genome sequence of a pathogen species to understand pathogen mechanisms. Comparative genomics is a methodology which allows scientists to compare the genomes of different species and strains. There are several examples of successful comparative genomics studies, among them the analysis of Listeria and Escherichia coli. Some studies have attempted to address the difference between pathogenic and non-pathogenic microbes. This inquiry proves to be difficult, however, since a single bacterial species can have many strains, and the genomic content of each of these strains varies. though it most likely involves adaptation to a new environment or ecological niche. Some researchers believe gene loss may actually increase fitness and survival among pathogens. and Yersinia pestis. It is of particular interest in microbial studies because these mobile genetic elements may introduce virulence factors into a new genome. A comparative study conducted by Gill et al. in 2005 postulated that LGT may have been the cause for pathogen variations between Staphylococcus epidermidis and Staphylococcus aureus. There still, however, remains skepticism about the frequency of LGT, its identification, and its impact. New and improved methodologies have been engaged, especially in the study of phylogenetics, to validate the presence and effect of LGT. Gene gain and gene duplication events are balanced by gene loss, such that despite their dynamic nature, the genome of a bacterial species remains approximately the same size. Genome rearrangement Mobile genetic insertion sequences can play a role in genome rearrangement activities. Pathogens that do not live in an isolated environment have been found to contain a large number of insertion sequence elements and various repetitive segments of DNA. and Burkholderia pseudomallei which have been shown to exhibit genome-wide rearrangements due to insertion sequences and repetitive DNA segments. SNPs play a key role in understanding how and why mutations occur. SNPs also allows for scientists to map genomes and analyze genetic information. The diversity within pathogen genomes makes it difficult to identify the total number of genes that are associated within all strains of a pathogen species. For this reason, it was necessary to introduce the concept of pan-genomes and core genomes. Pan-genome and core genome literature also tends to have a bias towards reporting on prokaryotic pathogenic organisms. Caution may need to be exercised when extending the definition of a pan-genome or a core-genome to the other pathogenic organisms because there is no formal evidence of the properties of these pan-genomes. A core genome is the set of genes found across all strains of a pathogen species. Recent discoveries show that the number of new species continue to grow with an estimated 1031 bacteriophages on the planet with those bacteriophages infecting 1024 others per second, the continuous flow of genetic material being exchanged is difficult to imagine. Pathogenicity islands and their detection are the focus of several bioinformatics efforts involved in pathogenomics. It is a common belief that "environmental bacterial strains" lack the capacity to harm or do damage to humans. However, recent studies show that bacteria from aquatic environments have acquired pathogenic strains through evolution. This allows for the bacteria to have a wider range in genetic traits and can cause a potential threat to humans from which there is more resistance towards antibiotics. Recently it has been shown that there are specific genes and cell surface proteins involved in the formation of biofilm. These genes and also surface proteins may be characterized through in silico methods to form an expression profile of biofilm-interacting bacteria. This expression profile may be used in subsequent analysis of other microbes to predict biofilm microbe behaviour, or to understand how to dismantle biofilm formation. == Host microbe analysis ==

Pathogens have the ability to adapt and manipulate host cells, taking full advantage of a host cell's cellular processes and mechanisms. The genomic expression studies will be complemented with protein-protein interaction networks studies. This has also been applied successfully is Drosophila. The diverse community within the gut has been heralded to be vital for human health. There are a number of projects under way to better understand the ecosystems of the gut. The sequence of commensal Escherichia coli strain SE11, for example, has already been determined from the faecal matter of a healthy human and promises to be the first of many studies. Through genomic analysis and also subsequent protein analysis, a better understanding of the beneficial properties of commensal flora will be investigated in hopes of understanding how to build a better therapeutic. Eco-evo perspective The "eco-evo" perspective on pathogen-host interactions emphasizes the influences ecology and the environment on pathogen evolution. In order for colonization to occur, there must be changes in biochemical makeup to aid survival in a variety of environments. This is most likely due to a mechanism allowing the cell to sense changes within the environment, thus influencing change in gene expression. Understanding how these strain changes occur from being low or non-pathogenic to being highly pathogenic and vice versa may aid in developing novel therapeutics for microbial infections. == Applications ==

Human health has greatly improved and the mortality rate has declined substantially since the second world war because of improved hygiene due to changing public health regulations, as well as more readily available vaccines and antibiotics. Pathogenomics will allow scientists to expand what they know about pathogenic and non-pathogenic microbes, thus allowing for new and improved vaccines. Methods of vaccine production, such as biochemical and serological, are laborious and unreliable. They require the pathogens to be in vitro to be effective. New advances in genomic development help predict nearly all variations of pathogens, thus making advances for vaccines. Following the sequencing of the Spanish influenza, the pathogen was also reconstructed. When inserted into mice, the pathogen proved to be incredibly deadly. Using technologies and insight gained from reconstruction of the Spanish influenza, it may be possible to prevent future deadly planted outbreaks of disease. There is a strong ethical concern however, as to whether the resurrection of old viruses is necessary and whether it does more harm than good. The best avenue for countering such threats is coordinating with organizations which provide immunizations. The increased awareness and participation would greatly decrease the effectiveness of a potential epidemic. An addition to this measure would be to monitor natural water reservoirs as a basis to prevent an attack or outbreak. Overall, communication between labs and large organizations, such as Global Outbreak Alert and Response Network (GOARN), can lead to early detection and prevent outbreaks. == See also ==