Type III Secretion System Project


We are studying the Type III Secretion System (T3SS) in bacteria. This system is a major virulence factor in species such as:
  • Shigella species, which contaminate food and cause bacillary dysentery, a severe diarrheal disease. Over 165 million cases are estimated annually, leading to over 1 million deaths.
  • E. coli -- causes food poisoning and diarrhea. One type of E. coli infects 200 miliion people annually, resulting in 380,000 deaths, mainly in developing nations.
  • Salmonella species, which cause diseases such as typhoid and paratyphoid fever, accounting for 30 million illnesses and and 250,000 deaths annually.
  • Yersinia pestis -- cause of plague, including the Black Death that resulted in the deaths of an estimated 30% of the European population in the 1300s.
  • Pseudomonas aeruginosa -- a major hospital-acquired pathogen that can be fatal and is highly resistant to antibiotics.
  • Chlamydia species, which are responsible for a major sexually transmitted disease as well as the leading cause of infectious blindness globally.
The T3SS is composed of syringe-like molecular machine that injects specific proteins (called effectors) into the cells of the host organism to promote virulence. For example, Salmonella utilize a T3SS to inject actin-rearranging effectors into epithelial cells which modify the structure of the cell membranes and allow Salmonella to enter the cells.

Our specific interest is the T3SS secretion signal -- the structural motif that the T3SS machinery uses to recognize and recruit effector proteins for secretion. We are interested in this interaction because it is a key event in the infection process and because disrupting this interaction could hypothetically destroy the bacteria's ability to invade host cells. The nature of the secretion signal is unknown. Not much is known about the three dimensional structure of the T3SS signal and indeed, opposing theories have been put forth in the literature. Understanding the secretion signal would be represent a significant advance in the study of bacterial pathogenesis and, as noted above, could open the way for a new type of antibiotic -- possibly a small molecule designed to disrupt the effector-T3SS binding interface. By folding of the proposed target peptides and other non-involved peptides as a test, we want to gain structural insight to the mechanism promoting the secretion.

Bacteria that use the Type III Secretion System for infection cause severe illness in hundreds of millions of humans every year and result in a substantial loss of life. Most of these cases are young children in developing nations. Individuals with compromised immune systems such as AIDS patients are also directly threatened by these diseases. The alarming rise of antibiotic resistance in bacteria has created an urgent situation that requires new methods to fight these bacteria. The World Health Organization has identified diarrheal disease as a major challenge to global health and is calling for the immediate development of new intervention strategies. Results from this POEM@HOME project may reveal new horizons for antibiotics development.

Nr.Energy User Progress
[kcal/mol]
P. 1-14.44MGeee
100%
P. 21.17ElmoHoo
100%
P. 3-26.21Henry
100%
P. 4-23.94georgios
100%
P. 5-21.75BenjaminH
100%
P. 6-4.38IceChant
100%
P. 7-20.95Anthrax
100%
P. 8-19.78Jennifer
100%
P. 9-19.47Jamrogie
100%
P. 10-1.54[AF>HFR] KronoMuldor
100%
P. 11-25.14Zachary@Teddies
100%
P. 12-23.06BF
100%
P. 13-23.52[ESL Brigade] Exi
100%
P. 14-9.74J0k3r
100%
P. 15-7.8Joerg Frings-Fuerst
100%
P. 16-6.19SWANT
100%
P. 17-15.5The Swordfish
100%
P. 18-9.7SchneiderScape
100%
P. 19-12.64ddranoc
100%
P. 20-4.42yamashin
100%
P. 21-14.32ashamar
100%
P. 22-12.31georgios
100%
P. 23-4.28ov
100%
P. 24-12.91Nico
100%
P. 25-31.1RvP_LaN
100%
P. 26-11.65asemann
100%
P. 27-36.06Rular
100%
P. 28-18.16Bob Bowen
100%
P. 29-26.97silentgecko
100%
P. 30-28.84palbarra
100%
P. 31-23.08carl.h
100%
P. 32-7.45Dan
100%
P. 33-30.49Eric
100%
P. 34-23.31SmokyRS
100%
P. 35-26.21DarkWaterSong
100%
P. 36-30.67CaptainMooseInc
100%
P. 37-22.49Otter
100%
P. 38-4.04Velociraptor
100%
P. 39-10.46[AF>HFR] KronoMuldor
100%
P. 40-2.49Dwain Dunn
100%
P. 41-25.65PJK
100%
P. 42-11.52Cluster Physik
100%
P. 434.08RAM_Germany
100%
P. 44-4.24Skip Da Shu
100%
P. 45-15.18Amar^
100%
P. 46-2.33Jordan
100%
P. 47-27.36slv
100%
P. 48-13.33J-R
100%
P. 49-7.88Nite Owl
100%
P. 50-6.57Liuqyn
100%
P. 51-20.95rufu
100%
P. 52-18.69SuperReal
100%
P. 53-28.5Digo
100%
P. 54-7.61[AF>EDLS>Biomed] Krest
100%
P. 55-22.57Jardik
100%
P. 56-7.38[GR] stefdur
100%
P. 572.93j2satx
100%
P. 58-9.27PJK
100%
P. 59-26.31Liebel-lab
100%
P. 60-25.89nicolasjeremy
100%
P. 61-21.44tuning
100%
P. 62-11.96Nite Owl
100%
P. 63-18.73Ditschezz
100%
P. 64-32.83carl.h
100%
P. 65-31.08jeidler
100%
P. 66-15.5ozizo
100%
P. 67-28.85FrankBeger
100%
P. 68-33.33Otter
100%
P. 69-22.86fRee@ESL
100%
P. 70-9.52[ESL ELITE CRUNCHER]  ScAnY
100%
P. 71-28.39BenjaminH
100%
P. 72-32.16Shiro Sumaro
100%
P. 73-15.81Nite Owl
100%
P. 74-11.44Woody Woodpecker
100%
P. 75-24.62Nightshift
100%
P. 76-30.02Jotam Felmy
100%
P. 77-21.4UNA
100%
P. 78-21.31jeidler
100%
P. 79-21.03Chaos01
100%
P. 80-27.95fnAc
100%
P. 81-21.34Zachary@Teddies
100%
P. 82-28.33John Mohr
100%
P. 83-12.03Reality Bytes
100%
P. 84-31.03[AF>HFR] KronoMuldor
100%
P. 85-23.24AndiDEG
100%
P. 86-29.15nati2020
100%
P. 87-20.42ampex189
100%
P. 88-33.18twelve_x
100%
P. 89-16.27jeidler
100%
P. 90-26.41ElmoHoo
100%
P. 91-21.99REM!X
100%
P. 92-21.43Ducati 749
100%
P. 93-20.79carl.h
100%
P. 94-23.48BruceS
100%
P. 950.77Joerg Frings-Fuerst
100%
P. 96-35.55fragle
100%
P. 975.28Nite Owl
100%
P. 98-10.48Fuzzyness..
100%
P. 99-15.57MGeee
100%
P. 100-18.73J-R
100%
P. 101-6.71j2satx
100%
P. 102-12.2georgios
100%
P. 103-26.99Ingorad
100%