The advent of whole genome sequencing has enabled microbiologists to determine the relationships between different pathogens, how these pathogens evolved, and to identify the key genes involved in pathogenicity. The sequence of 16S (bacterial) and 18S (eukaryotic) rRNA can be used to identify related organisms and the analysis of DNA from skeletons or tissue samples of known age can be used to determine when these organisms diverged (molecular clock analysis). DNA analysis also can be used to detect horizontal gene transfer, the movement of genetic material between unicellular and/or multicellular organisms other than by reproduction, and the most important factor in the evolution of many microorganisms. The evidence for horizontal gene transfer includes the detection of bacteriophage remnants, differences in %GC composition, and groups of genes involved in pathogenicity flanked by insertion sequences (genomic islands, pathogenicity islands).
1. Gene Manipulation: An All-Embracing Technique 2. Basic Techniques 3. Cutting And Joining DNA Molecules 4. Basic Biology Of Plasmid And Phage Vectors 5. Cosmids, Phasmids And Other Advanced Vectors 6. Cloning Strategies 7. Sequencing And Mutagenesis 8. Cloning In Bacteria Other Than E. Coli 9. Cloning In Saccharomyces Cerevisiae And Other Fungi 10. Gene Transfer To Animal Cells 11. Genetic Manipulation Of Animals 12. Gene Transfer To Plants 13. Advances In Transgenic Technology 14. Applications Of Recombinant DNA Technology.
Morbilliviruses are RNA viruses that infect humans and a wide variety of domestic and wild animals. They are highly infectious, spread via the respiratory route, cause immune suppression, and are associated with high morbidity and mortality. The best-known examples are measles, rinderpest, and canine distemper. Rinderpest is a disease of cattle and other ungulates. It is believed to have evolved in Asia around the time that humans transitioned from hunter gatherers to farmers. Invading armies brought the disease to the West with their animals. The European colonialists then took the disease to Africa. The disease now has been eliminated by vaccination. Measles is highly infectious and one of the leading causes of death among young children. Maintenance of measles virus in a population requires a constant supply of susceptible individuals. Vaccination is very effective at preventing the disease but misplaced anti-vaccination campaigns are resulting in a surge in cases. Measles was introduced to the Americas, with devastating effects, by early colonialists. By contrast, canine distemper was absent from Europe in the pre-Columbian era. The dogs of colonialists caught the virus in the Americas and brought it to Europe. It is believed that measles arose when rinderpest jumped species. Sequence analysis of different morbilliviruses shows that it would take only a few mutations for them to jump species.
Neisseria meningitidis and Neisseria gonorrhoeae are the only Neisseria species to cause infections in immune competent individuals. The gonococcus has existed for thousands of years but the meningococcus emerged about 400 years ago. Both bacteria use phase variation of surface antigens to escape host defences. Both bacteria are naturally competent for transformation and the large number of DNA uptake sequences in their genomes indicate that they have acquired a lot of genes by horizontal gene transfer. A key virulence determinant of the meningococcus is the capsule and the ability to synthesize it was acquired from the unrelated Haemophilus influenzae. Because of its importance, the capsule has been used in the development of vaccines. Meningococci produce many virulence factors, but how these help the bacteria to invade the bloodstream is not known. Gonococci can exist both extracellularly and intracellularly. When residing extracellularly the gonococci attract neutrophils and these constitute most of the characteristic discharge seen in patients with gonorrhoea. Numerous virulence factors prevent destruction of the bacteria on the mucosal surface. The PorA protein probably plays a key role in internalization.
Escherichia coli normally behaves as a commensal organism and constitutes about 0.1% of the normal flora of the human gut where its beneficial properties include synthesis of vitamin K. Some strains of Escherichia coli can cause disease and these pathogenic strains have acquired various pathogenicity determinants, most likely by horizontal gene transfer. The diseases caused by Escherichia coli fall into two types: intestinal diseases and non-intestinal diseases. The latter type includes urinary tract infections and neonatal meningitis. There are seven different types of intestinal disease caused by Escherichia coli and each type is caused by a different pathovar with unique virulence determinants. Based on genome analysis, the bacteria formerly classified as Shigella species are simply pathovars of Escherichia coli. Some Escherichia coli strains can increase their virulence by inactivating certain chromosomal genes, a process known as pathoadaptation, and this may occur by movement of insertion sequences.
This chapter contains section titled: Introduction Recombinant DNA technology From recombinant DNA to molecular medicine Gene medicine Disease models The impact of genomics on medicine The new molecular medicine Outline of this book
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