Department of Bacterial Infections

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Research Group

Research Projects

This department focuses on the pathogenic mechanisms of infectious bacteria, particularly bacterial enteropathogens such as enteropathogenic Escherichia coli, Vibrio spp. and Aeromonas spp.

Current subjects of research are:

  1. Analysis of colonization factors of enteropathogens and their host receptors.
  2. Molecular biological analysis of the protein toxins produced by various enteropathogens.
    These studies should provide important information for the development of new drugs and vaccines.
  3. Analysis of the structure and function of the typeIII secretion system (T3SS) and the pathogenic mechanism by which its effectors are injected into target cells.
  4. Development of rapid detection and identification tests for various pathogens according to immunological and molecular genetic principles.
  5. A study of hospital-acquired infections and a molecular epidemiological study performed in the Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI) in Thailand are also being conducted.
Fig.1

Fig.1.
CFA/III-mediated adherence of enterotoxigenic Escherichia coli to the intestinal epithelium, as observed by SEM.

Fig.2

Fig.2.
Analysis of the diarrheagenic activity of Vibrio parahaemolyticus mutants by using the rabbit ileal loop test. This analysis shows that T3SS-2 and its effector are important for enterotoxcity.
Sample¡Êfrom upper left¡Ë ¡¨ 1. WT, 2. ¦¤TTSS1, 3. ¦¤TTSS2, 4. ¦¤TTSS1/2, 5. ¦¤tdhAS, 6. ¦¤tdhAS, ¦¤TTSS1, 7. ¦¤tdhAS, ¦¤TTSS2, 8. ¦¤tdhAS, ¦¤TTSS1/2, 9. Non-Infection

Fig.3

Fig.3. Schematic depiction of AexU internalization and cytotoxicity events:
AexU is translocated and secreted by Aeromonas T3SS (1,2), which recognizes ¦Á6¦Â4-integrin receptors (3). The activation of ¦Â4-integrin selectively activates Rac1 (4), which induces membrane ruffles and macropinocytosis (5). Rab8-associated macropinosomes then enclose AexU and endocytose it before fusing into tubules (6) that move toward the cell center (7) where AexU preferentially localizes in the endoplasmic reticulum (ER). Calnexin assists AexU folding and the assembled AexU then proceeds further along the secretory pathway (8). AexU again uses Rab8 to recycle back to the plasma membrane and inactivates the membrane-associated active Rac1 (9), which leads to progressive Rac1-dependent cytoskeletal disruptions. The AexU-containing vesicles then bud out from the affected cell (10). If the cell is mitotically active, AexU accumulates between the daughter cells in the telophase of mitosis and prevents their dissociation, thereby resulting in two firmly attached cells (11).


Major publications

  1. Bhattacharjee, R. N., Park, K. S., Uematsu, S., Okada, K., Hoshino, K., Takeda, K., Takeuchi, O., Akira, S., Iida, T. and Honda, T.(2005). Escherichia coli verotoxin 1 mediates apoptosis in human HCT116 colon cancer cells by inducing overexpression of the GADD family of genes and S phase arrest. FEBS Lett. 579, 6604-6610.
  2. Vlademir, C., Kodama, T., Nijstad, N., Abolghait, S. K., Iida, T. and Honda, T.(2006). Cortactin is essential for F-actin assembly in enteropathogenic E, coli(EPEC)- and enterohaemorrhagic E. coli (EHEC)-induced pedestals and the ¦Á-helical region is involved in the localization of cortactin to bacterial attachment sites. Cellular Microbiology. 8, 769-780.
  3. Ono, T., Park, K. S., Ueta, M., Iida, T. and Honda, T.(2006). Identification of proteins secreted via Vibrio parahaemolyticus TypeIII secretion system 1. Infect. Immun. 74, 1032-1042.
  4. Vlademir, C., Kodama, T., Nijstad, N., Abolghait, S. K., Nada, S., Okada, M., Iida, T. and Honda, T.(2007). Throsine phosphorylation controls cortactin binding to two enterohaemorrhagic Escherichia coli effectors:Tir and EspFu/TccP. Cellular Microbiology. 9, 1782-1795.
  5. Gao, F., Kodama, T., Chen, X., Okada, K. and Honda, T.(2007). A targeting approach for delivery of polymer microparticle-antibody conjugate against Vibrio parahaemolyticus-induced cytotoxicity to human intestinal epithelial cells. Journal of Drug Targeting. 15, 428-436.

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