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Hiroki Takahashi

Position Professor
Research Projects Project for Host Response Network of Bacterial Infection
Division Division of Clinical Research
TEL +81 43 226 2499
FAX +81 43 226 2486
E-mail tomoko-y[at]


Bacteriology, Infection Biology

Main topics of research

The research subjects is
Dissecting the molecular mechanisms of systemic infection and persistent infection by facultative intracellular bacteria through the study of Salmonella-host interplay: We focus on the Salmonella effectors, which we have identified through a meta-analytic approach to the accurate prediction of effectors, to elucidate the dynamic interplay with their host targets and bacterial strategies for withstanding the host innate- and acquired-immune systems.

Main publications

  1. Takaya A, Yamamoto T, Tokoyoda K. Humoral immunity versus Salmonella. Frontiers in Immunology, in press (2020)
  2. Männe C, Takaya A, Yamasaki Y, Mursell M, Hojyo S, Wu T, Sarkander J, McGrath M, Cornelis R, Hahne S, Cheng Q, Kawamoto T, Hiepe F, Kaufmann S, Yamamoto T, Radbruch A, Tokoyoda K: Salmonella SiiE prevents an efficient humoral immune memory by interfering with IgG+ plasma cell persistence in the bone marrow. Proc Natl Acad Sci USA, 116(15) 7425-7430, 2019.
  3. Takaya A, Takeda H, Tashiro S, Kawashima H, Yamamoto T: Chaperone-mediated secretion switching from early to middle substrates in the type III secretion system encoded by Salmonella pathogenicity island 2. J Biol Chem, 294(10) 3783-3793, 2019.
  4. Imamura K, Takaya A, Ishida Y, Fukuoka Y, Taya T, Nakaki R, Kakeda M, Imamachi N, Sato A, Yamada T, Onoguchi-Mizutani R, Akizuki G, Tanu T, Tao K, Miyao S, Suzuki Y, Nagahama M, Yamamoto T, Jensen TH, Akimitsu N: Diminished nuclear RNA decay upon Salmonella infection upregulates antibacterial noncoding RNAs. EMBO J, 37(13). pii: e97723, 2018.
  5. Xu J, Suita K, Okuno K, Takaya A, Yamamoto T, Isogai E: Membrane vesicle protein PagC as a novel biomarker for detecting pathogenic Salmonella in the viable but not culturable state. J Vet Med Sci, 80(1):133-137, 2018.
  6. Takeuchi N, Ohkusu M, Hoshino T, Naito S, Takaya A, Yamamoto T, Ishiwada N. Emergence of quinolone-resistant strains in Streptococcus pneumoniae isolated from paediatric patients since the approval of oral fluoroquinolones in Japan. J Infect Chemother, 23(4):218-223, 2017.
  7. Ishiwada N, Takaya A, Kimura A, Watanabe M, Hino M, Ochiai H, Matsui M, Shibayama K, Yamamoto T. Linezolid-resistant Staphylococcus epidermidis associated with long-term, repeated linezolid use in a pediatric patient. J Infect Chemother, 22(3):187-90, 2016.
  8. Shoji T, Takaya A, Sato Y, Kimura S, Suzuki T, Yamamoto T. RlmCD-mediated U747 methylation promotes efficient G748 methylation by methyltransferase RlmAⅡ in 23S rRNA in Streptococcus pneumoniae; interplay between two rRNA methylations responsible for telithromycin susceptibility. Nucleic Acids Research, 43(18):8964-72 (2015).
  9. Takaya A, Kimura A, Sato Y, Ishiwada N, Watanabe M, Matsui M, Shibayama K, Yamamoto T. Molecular characterization of linezolid-resistant coagulase-negative Staphylococcus isolates in Japan. J Atimicrob Chemother, 70(3):658-63 (2015).
  10. Matsui H, Fukiya S, Kodama-Akaboshi C, Eguchi M, Yamamoto T. Mouse models for assessing the cross-protective efficacy of oral non-typhoidal Salmonella vaccine candidates harbouring in-frame deletions of the ATP-dependent protease lon and other genes. J Med Microbiol, 64:295-302 (2015).
  11. Hirai S, Yokoyama E, Etoh Y, Seto J, Ichihara S, Suzuki Y, Maeda E, Sera N,Horikawa K, Sato S, Yamamoto T. Putative classification of clades of enterohemorrhagic Escherichia coli O157 using an IS-printing system. Lett Appl Microbiol, 61:267-273. (2015).
  12. Takeuchi M, Yamamoto T. Apoptosis induced by NAD depletion is inhibited by KN-93 in aCaMKII-independent manner. Exp Cell Res, 335:62-67(2015).
  13. Sato Y, Takaya A, Mouslim C, Hughes K.T., Yamamoto T. FliT selectively enhances proteolysis of FlhC subunit in FlhD4C2 complex by an ATP-dependent protease ClpXP. J Biol Chem, 289(47):33001-11 (2014).
  14. Takeuchi M, Niimi T, Matsumoto M, Orita M, Yokota H, Yamamoto T. Discovery of a novel nicotinamide phosphoribosyl transferase (NAMPT) inhibitor via in silico screening. Biol Pharm, 37:31-36 (2014)
  15. Etoh Y, Hirai S, Ichihara S, Maeda E, Yokoyama E, Sera N, Horikawa K, Yamamoto T. Evolutionary model of the divergence of enterohemorrhagic Escherichia coli O157 lineage I/II clades reconstructed from high resolution melting and Shiga-like toxin 2 analyses. Infect Genet Evol, 24:140-145(2014).
  16. Hirai S, Yokoyama E, Etoh Y, Seto J, Ichihara S, Suzuki Y, Maeda E, Sera N, Horikawa K, Yamamoto T. Analysis of the population genetics of clades of enterohaemorrhagic Escherichia coli O157:H7/H- isolated in three areas in Japan. J Appl Microbiol, 117:1191-1197 (2014)
  17. Takaya A, Sato Y, Shoji T, Yamamoto T. Methylation of 23S rRNA nucleotide G748 by RlmAII methyltransferase renders Streptococcus pneumoniae telithromycin susceptible. Antimicoriol agents Chemother, 57:3789-3796 (2013)
  18. Sugisaki K, Hanawa T, Yonezawa H, Osaki T, Fukutomi T, Kawakami H, Yamamoto T, Kamiya S. Role of (p)ppGpp in biofilm formation and expression of filamentous structures in Bordetella pertussis. Microbiology, 159:1379-89(2013).
  19. Hirai S, Yokoyama E, Yamamoto T. Linkage disequilibrium of the IS629 insertion among different clades of enterohemorrhagic Escherichia coli O157:H7/H-strains. Infection, Genetics and Evolution, 18:94-9(2013).
  20. Yamamoto T. Studies on the molecular mechanism of Salmonella infection. Antibiotics and Chemotherapy, 29: 473-483 (2013)
  21. Takaya A. Regulation of Salmonella pathogenesis by effectors of Salmonella pathogenicity island 1 and 2. Antibiotics and Chemotherapy, 29: 62-71(2013)
  22. Takaya A, Erhardt M, Karata, K, Winterberg K, Yamamoto T, Hughes, KT. YdiV: a dual function protein that targets FlhDC for ClpXP-dependent degradation by promoting release of DNA-bound FlhDC complex. Mol Microbiol, 83(6):1268-1284 (2012)
  23. Sato Y, Takaya, Yamamoto T. Meta-analytic approach to the accurate prediction of secreted virulence effectors in gram-negative bacteria. BMC Bioinformatics, 12:442(2011)
  24. Kitagawa R, Takaya A, Yamamoto T. Dual regulatory pathways of flagellar gene expression by ClpXP protease in enterohaemorrhagic Escherichia coli. Microbiology, 157:3094-3103(2011)
  25. Kitagawa R, Takaya A, Ohya M, Mizunoe Y, Takade A, Yoshida SI, Isogai E, Yamamoto T. Biogenesis of Salmonella enterica serovar Typhimurium Membrane Vesicles Provoked by Induction of PagC. J Bacteriol, 192 (21) 5645-5656 (2010).
  26. Takaya A, Kitagawa N, Kuroe Y, Endo K, Okazaki M, Yokoyama E, Wada A, Yamamoto T. Mutational analysis of reduced telithromycin suspetibility of Streptococcus pneumonia isolated clinically in Japan. FEMS Microbiol Lett 307 (1) 87-93 (2010).
  27. Matsui M, Takaya A, Yamamoto T. Sigma32-mediated negative regulation of Salmonella pathogenicity island 1 expression. J Bacteriol, 190(20): 6636-6645 (2008).
  28. Mizusaki H, Takaya A, Yamamoto T, Aizawa S. Signal pathway in salt-activated expression of the Salmonella pathogenicity island 1 type III secretion system in Salmonella enterica serovar Typhimurium. J Bacteriol, 190(13): 4624-4631 (2008).
  29. Okumura R, Hirata T, Onodera Y, Hoshino K, Otani T, Yamamoto T. Dual-targeting properties of the 3-aminopyrrolidyl quinolones, DC-159a and sitafloxacin, against DNA gyrase and topoisomerase IV: contribution to reducing in vitro emergence of quinolone-resistant Streptococcus pneumonia. J Antimicrob Chem, 62(1): 98-104 (2008).
  30. Takaya A, Tabuchi F, Tsuchiya H, Isogai E, Yamamoto T. Negative regulation of quorum sensing systems in Pseudomonas aeruginosa by ATP-dependent Lon protease. J Bacteriol, 190(12): 4181-4188 (2008).
  31. Kage H, Takaya A, Ohya M, Yamamoto T. Coordinated regulation of expression of Salmonella Pathogenicity Island 1 and flagellar type III secretion systems by ATP-dependent ClpXP protease. J. Bacteriol, 190(7): 2470-2478 (2008).
  32. Hang’ombe BM, Isogai E, Mubita C, Isogai N, Silungwe M, Chisenga C, Moonga L, Mulenga E, Yabe J, Takaya A, Yamamoto T, Kurebayashi Y, Isogai H. Detection of invA, spiC, sipC, invF, and hilA in Salmonella Isolated from beef and poultry by dot blot hybridization in Zambia. Int J Appl Res Vet Med, 6(1): 1-6 (2008).
  33. Eguchi M, Sekiya Y, Kikuchi Y, Takaya A, Yamamoto T, Matsui H. Expressed Salmonella antigens within macrophages enhance the proliferation of CD4+ and CD8+ T lymphocytes by means of bystander dendritic cells. FEMS Immunol Med Microbiol, 50(3):411-20 (2007).
  34. Yokoyama E, Maruyama S, Kabeya H, Hara S, Sata S, Kuroki T, Yamamoto T. Prevalence and Genetic Properties of Salmonella enterica Serovar Typhimurium Definitive Phage Type 104 Isolated from Rattus norvegicus and Rattus rattus House Rats in Yokohama City, Japan. Appl Environ Microbiol, 73:2624-2630 (2007).
  35. Takaya A, Watanabe M, Yamamoto T. Organization of Tn2610 containing two transposition modules. Antimicrob Agents Chemother, 50: 1143-1147 (2006).
  36. Takaya A, Matsui M, Tomoyasu T, Kaya M, Yamamoto T. The DnaK chaperone machinery converts the native FlhD2C2 heterotetramer into a functional transcriptional regulator of flagellar regulon expression in Salmonella. Mol Microbiol, 59: 1327-1340 (2006).
  37. Sasaki Y, Kai A, Hayashi Y, Shinkai T, Noguchi Y, Hasegawa M, Sadamasu K, Mori K, Tabei Y, Nagashima M, Morozumi S, Yamamoto T. Multiple viral infections and genomic divergence among noroviruses during an outbreak of acute gastroenteritis. J Clin Microbiol, 44(3): 790-797 (2006).
  38. Kodama C, Eguchi M, Sekiya Y, Yamamoto T, Kikuchi Y, Matsui H. Evaluation of the Lon-deficient Salmonella strain as an oral vaccine candidate. Microbiol Immunol, 49: 1035-1045 (2005).
  39. Tomoyasu T, Takaya A, Handa Y, Karata K, Yamamoto T. ClpXP controls the expression of LEE genes in enterohaemorrhagic Escherichia coli. FEMS Microbiol Lett, 253:59-66 (2005).
  40. Takaya A, Kubota Y, Isogai E, Yamamoto T. Degradation of the HilC and HilD regulator proteins by ATP-dependent Lon protease leads to down-regulation of Salmonella pathogenicity island 1 gene expression. Mol Microbiol, 55: 839-852 (2005).
  41. Takaya A, Suzuki A, Kikuchi Y, Eguchi M, Isogai E, Tomoyasu T, Yamamoto T. De-repression of Salmonella pathogenicity island 1 genes within macrophages leads to rapid apoptosis via caspase-1 and caspase-3-dependent pathway. Cell Microbiol, 7: 79-90 (2005).
  42. Shibazaki M, Tanaka K, Nagai K, Watanabe M, Fujita S, Suzuki K, Okada G, Yamamoto T. YM-92447 (spinosulfate A), a neuraminidase inhibitor produced by an unidentified pycnidial fungus. J Antibiotics, 57: 812-815 (2004).
  43. Shibazaki M, Taniguchi M, Yokoi T, Nagai K, Watanabe M, Suzuki K, Yamamoto T. YM-215343, a novel antifungal compound from Phoma sp. QN04621. J Antibiotics, 57: 379-382 (2004).
  44. Takaya A, Tomoyasu T, Matsui H, Yamamoto T. The DnaK/DnaJ chaperone machinery of Salmonella enterica serovar Typhimurium is essential for invasion of epithelial cells and survival in macrophages, leading to systemic infection. Infect Immun, 72: 1364‐1373 (2004).
  45. Tomoyasu T, Takaya A, Sasaki T, Nagase T, Kikuno R, Morioka M, Yamamoto T. A new heat-shock gene agsA, which encodes a small chaperone involved in suppressing protein aggregation in Salmonella enterica serovar Typhimurium. J Bacteriol, 185: 6331-6339. (2003).
  46. Shibazaki M, Yamaguchi H, Sugawara T, Suzuki K, Yamamoto T. Microbial glycosylation and acetylation of brefeldin A. J Biosci Bioeng, 96: 344-348. (2003).
  47. Yamaguchi,Y, Tomoyasu T, Takaya A, Morioka M, Yamamoto T. Effects of disruption of heat shock genes on susceptibility of Escherichia coli to fluoroquinolones. BMC Microbiology, 3:16.(2003).
  48. Tomoyasu T, Takaya A, Isogai E, Yamamoto T. Turnover of FlhD and FlhC, master regulator proteins for Salmonella flagellum biogenesis, by the ATP-dependent ClpXP protease. Mol Microbiol, 48: 443-452. (2003).
  49. Takaya A, Suzuki M, Matsui H, Tomoyasu T, Sashinami H, Nakane A, Yamamoto T. Lon, a stress-induced ATP-dependent protease is critically important for the systemic Salmonella infection of mice. Infect Immun, 71: 690-696 (2003).
  50. Matsui H, Suzuki M, Isshik Y, Eguchi M, Kikuchi Y, Motokawa K, Takaya A, Tomoyasu T, Yamamoto T. Oral immunization with ATP-dependent protease-deficient mutants protects mice against subsequent oral challenge with virulent Salmonella enterica serovar Typhimurium. Infect Immun, 71: 30-39 (2003).
  51. Hanawa T, Yamanishi S, Murayama S, Yamamoto T, Kamiya S. Participation of DnaK in expression of genes involved in virulence of Liseria monocytogenes. FEMS Microbiol Lett, 214: 69-75 (2002).
  52. Takaya A. Tomoyasu T, Tokumitsu A, Morioka M, Yamamoto T. The ATP-dependent Lon protease of Salmonella enterica serovar Typhimurium regulates invasion and expression of genes encoded on Salmonella pathogenicity island 1. J Bacteriol, 184: 224-232 (2002).
  53. Tomoyasu T, Ohkishi T, Ukyo Y, Tokumitsu A, Takaya A, Suzuki M, Sekiya K, Matsui H, Kutsukake K, Yamamoto T. The ClpXP ATP-dependent protease regulates flagellum Synthesis in Salmonella enterica serovar Typhimurium. J Bacteriol, 184: 645-653(2002).
  54. Yamamoto T, Sashinami H, Takaya A, Tomoyasu T, Matsui H, Kikuchi Y, Hanawa T, Kamiya S, Nakane A. Disruption of the genes for ClpXP protease in Salmonella enterica serovar Typhimurium results in persistence requires endogenous gamma interferon and tumor necrosis factor alpha. Infect Immun, 69: 3164-3174(2001).