10 most common STDs… Syphilis Chlamydia Gonorrhea Herpes HIV/AIDS Hepatitis Genital warts Cervical cancer Chancroid Pubic lice & scabies Trichomoniasis STDs are a major issue in the US CDC estimates that there are approximately 19 million new cases of STDs each year in the United States, almost half of them among young people ages 15 to 24. STDs have an economic impact: direct medical costs associated with STDs in the United States are estimated at $16.4 billion annually.
Inflammation of the urethra Symptoms: Spontaneous urethral discharge Painful urination Pain/swelling of testicles Consequences: Spread to prostate and testes Infertility Transmission to female partners Incidence: In the US, incidence of urethritis is 4 million cases each year, and incidence of gonococcal urethritis is 650,000 cases each year; internationally, the incidence of gonococcal urethritis is 62 million per year, and incidence of non-gonococcal urethritis is 89 million each year (Terris).
Upper tract – Pelvic inflammatory disease Symptoms: Lower abdominal or low back pain Heavy vaginal discharge Irregular menstrual cycles Painful intercourse Fever & fatigue Generally asymptomatic Endometritis: inflammation of the endometrium Salpingitis: inflammation of Fallopian tubes Consequences: Tubal-factor infertility Peritonitis Septicemia Ectopic pregnancy Biological differences between women and men. Female health consequences are more severe Infections often go undiagnosed: Half of new gonorrhea cases and more than half of new chlamydia cases remain undiagnosed and unreported. For women, when untreated… 10-20% of chlamydia or gonorrhea infections can result in pelvic inflammatory disease PID can lead to long-term complications, such as… Chronic pelvic pain, ectopic pregnancy and infertility. Untreated STDs: cause at least 24,000 women to become infertile each year in the United States. t
Is a Mycoplasma species associated with male urethritis? Mycoplasma genitalium isolated in 1981 from two men with non-specific urethritis [Tully, et al 1981] Is M. genitalium a novel cause of reproductive tract disease? Extremely fastidious organism Less than 20 clinical strains available Epidemiological studies rely on PCR technology Association with disease: Urethritis Cervicitis Endometritis Pelvic inflammatory disease Tubal-factor infertility Pre-term birth Enhanced HIV shedding Chronic urethritis and cervicitis Extremely fastidious Small cellular size No cell wall Alternative genetic code Minimal genome Reduced evolution 1/8 the size of E. coli Smallest genome of any self-replicating organism Missing and/or absent cellular pathways and functions
Commercial sex workers Nairobi, Kenya Longitudinal sample set: Cervical samples collected at ~3 month intervals Women followed for up to 3 years Long-term M. genitalium infection: 20% of Mg-positive women with persistent infection ( ≥ 6 months)
Mycoplasma genitalium has a genome 1/8 the size of E. coli!!!! When they sequenced the genome they found only 521 genes, with only ~480 predicted to encode proteins. Mutagenesis studies in the late 1990’s showed that ~ 380 of these genes were “essential”
For 15 years, J. Craig VENTER has chased a dream: to build a genome from scratch and use it to make SYNTHETIC LIFE . \\ It was achieved at great expense, an estimated $40 million, and effort, 20 people working for more than a decade. On 20 May 2010 they reported success with a similar process, using instead the genome of Mycoplasma mycoides, creating what some called the first artificial life.  They describe the stepwise creation of a bacterial chromosome and the successful transfer of it into a bacterium, where it replaced the native DNA. Powered by the synthetic genome, that microbial cell began replicating and making a new set of proteins Despite this success, creating heavily customized genomes, such as ones that make fuels or pharmaceuticals, and getting them to &quot;boot&quot; up the same way in a cell is not yet a reality. &quot;
1. The Little Pathogen that Could Stefanie Iverson Cabral, PhD Totten Lab, Harborview Medical Center University of Washington Department of Medicine
2. The Little Pathogen that Could Mycoplasma genitalium <ul><li>Novel cause of reproductive tract disease </li></ul><ul><li>Minimal Microbe </li></ul><ul><li>Synthetic biology </li></ul>
3. Let’s talk about sex…
4. Male Urethritis Neisseria gonorrhoeae Chlamydia trachomatis Escherichia coli Herpes simplex virus 50% of male urethritis cases have an unknown cause!
5. Female Reproductive Tract Disease Neisseria gonorrhoeae Chlamydia trachomatis Escherichia coli Herpes simplex virus 60-70% of female cervicitis cases have an unknown cause!
6. Mycoplasma genitalium
7. Mycoplasma genitalium Persistence Cohen, et al. (2007) Sex Trans Dis. 34:274 Chronic infection = Mechanism(s) for immune evasion?
8. Who you calling “genomically reduced”?
10. Size doesn’t matter… <ul><li>4,639,675 base pairs </li></ul><ul><li>4267 genes </li></ul>E. coli <ul><li>580,076 base pairs </li></ul><ul><li>521 genes </li></ul>Mycoplasma genitalium Escherichia coli
14. Frankenstein Microbiology Cells are the basic unit of life. Cells contain DNA. All of the DNA in a cell is a genome. DNA contains the instructions for life. Scientists first create synthetic DNA genome. A series of chemical reactions to “grow” DNA outside of a cell to produce an entire genome.
15. Scientists will order custom genomes. Craig Venter & the first-ever living organism made entirely of novel synthetic DNA. Mycoplasma genitalium as a template. Strip down Mycoplasma genitalium genome and then re-build using synthetic DNA. . Add human genes to “ minimal” bacterial genome. Synthia is born….
17. Science. 2010. 329:52-56
18. Science. 2010. 329:52-56
19. The Little Pathogen that Could Mycoplasma genitalium <ul><li>Novel cause of reproductive tract disease </li></ul><ul><li>Minimal Microbe </li></ul><ul><li>Synthetic biology </li></ul>