| Project/Area Number |
16590362
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Kochi University |
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Principal Investigator |
TAKEUCHI Hiroaki Kochi University, Dept.Clinical Laboratory Medicine, Assistant Prof., 医学部附属病院, 講師 (90346560)
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| Co-Investigator(Kenkyū-buntansha) |
KUMON Yoshitaka Kochi University, Dept.Laboratory Medicine, Associate Prof., 医学部, 助教授 (40215033)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | H.pylori cdrA / Suppression of cell division / Morphology / Antimicrobial susceptibility / Immune response / Induction of IL-8 (in vitro, vivo) / persistent infection / High risk strain / Helicobacter pylori / H.pylori cdrA(細胞分裂関連遺伝子) / IL-8分泌量(vitro,vivo) / 遺伝子多型性 / 形態 / PBP |
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| Research Abstract |
We analyzed the function and role of H.pylori cdrA (cell division-related gene A), an unique gene involved in suppression of cell division and growth, which is considered to associate with persistent infection of H.pylori in the human stomach. The research results obtained from the comparative investigations between cdrA-disrupted mutant (HPKT510) and wild (HPK5) strains were summarized as follows ;
1.H.pylori cdrA is involved in cell elongation and death. The cdrA-disrupted mutant has potential to long survive compared to wild strain. 2.H.pylori cdrA is involved in maintain of its morphology. The cdrA-disrupted mutant is significantly shorter rod with slightly thicker space in cytoplasm than wild strains by electro-microscopic observations. Almost wild strain converted into coccoid, aggregation and lyses leading to death, but some cdrA-disruptant shows still short rod even in the late stationary phage. 3.Inactivation of cdrA influences PBPs profiles (proportion of major PBPs (1-3) and
… More
minor PBP4). 4.The cdrA-disruptant becomes tolerant against to beta-lactum antibiotics derivatives, ampicillin and amoxicillin. 5.The cdrA genetic types among strains were classified as one of four types : type I (like HPK5), II (like J99 and 26695), III and IV. The cdrA-functional strain is belonged in I and II, prevalence strain in Japan, but cdrA-dysfunctional strain is included in III and IV, prevalence strains in USA. 6.Both strains (HPK5 and HPKT510) induce IL-8 secretion from AGS cell however, the level of IL-8 induced by HPKT510 is significantly lower than HPK5 (corresponding to 50-60% of those induced by HPK5). Furthermore, these are consistent with the results from in vivo experiments using biopsy specimens in patients infected with between cdrA-functional (cdrA type I and II) or -disfunctional (cdrA type III and IV) strains. 7.The status of H.pylori pathogen CagA shows no differences between wild (HPK5) and its isogenetic cdrA-disrupted mutant (HPKT510) strains.
Taken together, H.pylori cdrA is involved in its morphology as well as viability due to maintain of cell division and growth. The cdrA lost in vivo could suggest that H.pylori may evade immune clearance and facilitate chronic persistent infection due to reduced secretion levels of proinflammatory cytokines such as IL-8 that are due to loss of edrA during infection. The CagA status of bath strains is no differences, suggesting that cdrA- cagA+ H.pylori stain is considered to be high risk strain in term of development of gastric disease due to persistent infection and pathogenesis Less
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