2003 Fiscal Year Final Research Report Summary
Investigation of antibiotic resistance by total analysis of cell wall biosynthesis in methicillin-resistant
| Project/Area Number |
14570238
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Bacteriology (including Mycology)
|
|---|
| Research Institution | HIROSHIMA UNIVERSITY |
|---|
Principal Investigator |
KOMATSUZAWA Hitoshi Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (90253088)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OHARA Masaru Hiroshima University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (80253095)
FUJIWARA Tamaki Hiroshima University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (90274092)
SUGAI Motoyuki Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (10201568)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Keywords | Staphylococcus aureus / vancomycin / methicillin / moenomycin / cell wall / transposon / antibiotic resistance / transglycosylase |
|---|
| Research Abstract |
We investigated the expression levels of 30 factors involved in cell wall biosynthesis by differential display method in methicillin/vancomycin-resistant and -sensitive Staphylococcus aureus, and found no difference between them. Since we previously found that vancomycin-intermediate S.aureus showed the moenomycin-resistance, we focused on two monofunctional transglycosylases, sgtA and sgtB. We constructed their knockout mutants and the mutants overexpressing SgtA or SgtB. Both overexpressed mutants showed the decreased susceptibility to moenomycin and vancomycin. Then, we isolated the moenomycin-resistant mutants from 5 clinical S.aureus strains, and found that all mutants showed decreased susceptibility to vancomycin and increased susceptibility to methicillin. However, these mutants did not alter the expression of SgtA and SgtB. These results indicate that SgtA and SgtB are associated with the susceptibility to vancomycin, but other factors are also involved. Then, we isolated two Tn551-insertional mutants, which increased the moenomycin-susceptibility. Both mutants also showed the decreased susceptibility to vancomycin. We identified the genes, lysC and fmtC, in which Tn551 inserted. lysC is involved in lysine biosynthesis, and fmtC is involved in the synthesis of lysyl-phosphatidylglycerol in bacterial membrane. These are novel factors affecting the vanocmycin-susceptibility in S.aureus
|
