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. 1-18.87UNA
100%
P. 2-12.07rufu
100%
P. 3-34.35MaxAMD400
100%
P. 4-28.36jeidler
100%
P. 5-20.54Tostada
100%
P. 6-25.51Tomasz R. Gwiazda
100%
P. 7-28.76UNA
100%
P. 8-13.87kockopes
100%
P. 9-10.42Linie
100%
P. 10-31.48MasteR
100%
P. 11-14.11Rular
100%
P. 12-26.93Christian Silenzi
100%
P. 13-32.17Mr. Ice
100%
P. 14-17.87[AF>HFR] KronoMuldor
100%
P. 15-35.46David
100%
P. 16-31.23sentient_life
100%
P. 17-19.16[MTB]JackTheRipper@Planet 3DNow!
100%
P. 18-10.45Jamrogie
100%
P. 19-36.27Avalon
100%
P. 20-19.71georgios
100%
P. 21-11.56Otter
100%
P. 22-38.2fragle
100%
P. 23-23.46Jamrogie
100%
P. 24-25.96Liebel-lab
100%
P. 25-36.16Nite Owl
100%
P. 26-16.11[AF>HFR>RR] Jim PROFIT
100%
P. 27-27.51BarryAZ
100%
P. 28-23.8Nite Owl
100%
P. 29-19.15Tostada
100%
P. 30-32.02gamer007
100%
P. 31-35.01DrPaua
100%
P. 32-31.34Tostada
100%
P. 33-33.89IndicaPurple
100%
P. 34-28.88Salva
100%
P. 35-35.942D
100%
P. 36-15.11Reality Bytes
100%
P. 37-12.1BLaCkHuNteR
100%
P. 38-27.7729bde
100%
P. 39-12.24Rular
100%
P. 40-38.17BF
100%
P. 41-31.18HumongousFungusAmongus
100%
P. 42-19.94sergi triguero
100%
P. 43-6.37puKE
100%
P. 44-28.81Otter
100%
P. 45-25.67N7VXJ
100%
P. 46-27.48Philipp
100%
P. 47-20.5FloTheBrain
100%
P. 48-22.12dbrookdale
100%
P. 49-26.93Mars
100%
P. 50-22.2short232
100%
P. 51-36.33ampex189
100%
P. 52-36.68REM!X
100%
P. 53-31.29DistroMan
100%
P. 54-9.71zYrEx
100%
P. 55-28.17BANZAI56
100%
P. 56-29.1729bde
100%
P. 57-12.27Nite Owl
100%
P. 58-23.29DistroMan
100%
P. 59-29.97rmcgill
100%
P. 60-20.85Tostada
100%
P. 61-29.36f.o.g.zone
100%
P. 62-18.15Rular
100%
P. 63-26.2Nite Owl
100%
P. 64-31.1Tostada
100%
P. 65-17.95AndiDEG
100%
P. 66-17.04Barraud Denis
100%
P. 67-32.26sentient_life
100%
P. 68-10.4f.o.g.zone
100%
P. 69-34.84carl.h
100%
P. 70-19.94georgios
100%
P. 71-42.36jghilino
100%
P. 72-44.62Gerry Rough
100%
P. 73-5.2UNA
100%
P. 74-36.21carl.h
100%
P. 75-37.63Beyond
100%
P. 76-14.48jghilino
100%
P. 77-22.08Michael Wolf
100%
P. 78-37.16Sofa King
100%
P. 79-8.49twelve_x
100%
P. 80-9.7Misanthrop66
100%
P. 81-38.6plonk420
100%
P. 82-12.39gork
100%
P. 83-32.34LCB001
100%
P. 84-33.42eric7
100%
P. 85-10.28[AF>Le_Pommier>MacBidouille.com] Fransoi78
100%
P. 86-31.53Philipp
100%
P. 87-36.31Chaos01
100%
P. 88-18.97Nite Owl
100%
P. 89-29.42JagDoc
100%
P. 90-38.36BarryAZ
100%
P. 91-17.83jeidler
100%
P. 92-30.98Nobody MK
100%
P. 93-25.54Morilu
100%
P. 94-20.58guru2001-muc
100%
P. 95-27.52jason1478963
100%
P. 96-41.99jeidler
100%
P. 97-19.05jeidler
100%
P. 98-20.72[AF>HFR] KronoMuldor
100%
P. 99-25.58Allen
100%
P. 100-37.02Tostada
100%
P. 101-42.25[AF>Le_Pommier>MacGeneration.com] kanak
100%
P. 102-34.06refler
100%
P. 103-38.4Thia
100%