1. Salmonella Typhi By Sandy Do

2. What is it? A bacteria A bacteria Causes typhoid fever that affects 16 million people annually and causes 600,000 fatalities Causes typhoid fever that affects 16 million people annually and causes 600,000 fatalities Has evolved the ability to spread from the intestine to the deeper tissues of humans, including the liver, spleen, and bone marrow Has evolved the ability to spread from the intestine to the deeper tissues of humans, including the liver, spleen, and bone marrow

3. What is it? Cont… Resistant to many drugs Resistant to many drugs Closely related to Salmonella typhimurium (also already sequenced), classified under the same species as Salmonella typhi Closely related to Salmonella typhimurium (also already sequenced), classified under the same species as Salmonella typhi Difference is that S. typhi causes typhoid fever and can only infect humans, whereas S. typhimurium causes food poisoning and can affect almost all animals Difference is that S. typhi causes typhoid fever and can only infect humans, whereas S. typhimurium causes food poisoning and can affect almost all animals

4. Where and When? Sequenced by the Sanger Institute Sequenced by the Sanger Institute On November 7, 2001 On November 7, 2001

5. Why? It affects millions of people and sequencing the genome can help us find a way to block its transmission in humans, eradicating it altogether It affects millions of people and sequencing the genome can help us find a way to block its transmission in humans, eradicating it altogether Can help improve diagnostic tools and vaccines Can help improve diagnostic tools and vaccines

6. Why? Multiple drug resistance (MDR) is a emerging problem in treating infectious diseases Multiple drug resistance (MDR) is a emerging problem in treating infectious diseases Salmonella typhi is one example of MDR microorganism Salmonella typhi is one example of MDR microorganism It is resistance to fluoroquinolones, the most effective antimicrobials for the treatment of typhoid fever It is resistance to fluoroquinolones, the most effective antimicrobials for the treatment of typhoid fever

7. So…..? Since salmonella typhi is an example of an emerging MDR microorganism, studying this genome can contribute to the understanding of how such microorganisms adapt rapidly to new environmental changes that are presented by modern human society. Since salmonella typhi is an example of an emerging MDR microorganism, studying this genome can contribute to the understanding of how such microorganisms adapt rapidly to new environmental changes that are presented by modern human society.

8. Some Statistics Chromosome sequence is 4,809,037 bp in length Chromosome sequence is 4,809,037 bp in length C+G content of 52.09% C+G content of 52.09% 4,599 protein-coding genes (402 of these are pseudogenes) 4,599 protein-coding genes (402 of these are pseudogenes)

9. Side Note: Pseudogene: once functional stretches of DNA that have been inactivated by mutation

10. Some Results The genome shows hundreds of deletions and insertions, resulting in MDR The genome shows hundreds of deletions and insertions, resulting in MDR Found the plasmid in Salmonella typhi that encodes resistances to all of the first-line drugs used for the treatment of typhoid fever Found the plasmid in Salmonella typhi that encodes resistances to all of the first-line drugs used for the treatment of typhoid fever Many other genes responsible for resistance in drugs were indentified Many other genes responsible for resistance in drugs were indentified

11. Side Note Plasmid: A piece of symbiotic DNA, mostly in bacteria but also in yeast, not forming part of the normal chromosome DNA of the cell and capable of replicating independently of it. Plasmids carry a signal situated at their replication origin dictating how many copies are to be made, and this number can be artificially increased. Plasmid: A piece of symbiotic DNA, mostly in bacteria but also in yeast, not forming part of the normal chromosome DNA of the cell and capable of replicating independently of it. Plasmids carry a signal situated at their replication origin dictating how many copies are to be made, and this number can be artificially increased.

12. Results Cont… Salmonella typhi’s genome gives us hints as to why it only infects humans Salmonella typhi’s genome gives us hints as to why it only infects humans Because it has 204 pseudogenes. Working versions of these genes were discarded during typhi’s evolution for its current habitat in humans Because it has 204 pseudogenes. Working versions of these genes were discarded during typhi’s evolution for its current habitat in humans Vs. typhimurium only has about 40 pseudogenes Vs. typhimurium only has about 40 pseudogenes

13. Results Cont… Both typhi and typhimurium have hundreds of genes that are different. This is very surprising because these two organisms are classified as a single species Both typhi and typhimurium have hundreds of genes that are different. This is very surprising because these two organisms are classified as a single species

14. Bibliography The Wellcome Trust Sanger Institute Website: http://www.sanger.ac.uk/Projects/S_typhi/ The Wellcome Trust Sanger Institute Website: http://www.sanger.ac.uk/Projects/S_typhi/ http://www.sanger.ac.uk/Projects/S_typhi/ Thain, M., Hickman, M. The Penguin Dictionary of Biology. New York: Penguin Books, 2000 Thain, M., Hickman, M. The Penguin Dictionary of Biology. New York: Penguin Books, 2000 Whitfield, John. (2001, October 25) “Salmonella Bacteria Sequenced” [Article posted on website] Whitfield, John. (2001, October 25) “Salmonella Bacteria Sequenced” [Article posted on website] http://www.nature.com/nsu/011025/011025-10.html http://www.nature.com/nsu/011025/011025-10.htmlhttp://www.nature.com/nsu/011025/011025-10.html “Complete Genome Sequence Of A Multiple Drug Resistance Salmonella enterica serovar Typhi CT18” “Complete Genome Sequence Of A Multiple Drug Resistance Salmonella enterica serovar Typhi CT18” http://www.nature.com/cgi- taf/DynaPage.taf?file=/nature/journal/v413/n6858/full/413848a0_fs.html http://www.nature.com/cgi- taf/DynaPage.taf?file=/nature/journal/v413/n6858/full/413848a0_fs.htmlhttp://www.nature.com/cgi- taf/DynaPage.taf?file=/nature/journal/v413/n6858/full/413848a0_fs.htmlhttp://www.nature.com/cgi- taf/DynaPage.taf?file=/nature/journal/v413/n6858/full/413848a0_fs.html “Complete genome sequence of Salmonella enterica serovar Typhimurium LT2” “Complete genome sequence of Salmonella enterica serovar Typhimurium LT2” http://www.nature.com/cgi- taf/DynaPage.taf?file=/nature/journal/v413/n6858/full/413852a0_fs.html http://www.nature.com/cgi- taf/DynaPage.taf?file=/nature/journal/v413/n6858/full/413852a0_fs.htmlhttp://www.nature.com/cgi- taf/DynaPage.taf?file=/nature/journal/v413/n6858/full/413852a0_fs.htmlhttp://www.nature.com/cgi- taf/DynaPage.taf?file=/nature/journal/v413/n6858/full/413852a0_fs.html