ID 110537
Title Transcription
ヤクザイ タイセイ コクフク ノ タメ ノ アタラシイ ホウホウ : MRSA ニ タイスル β‐ラクタムザイ カンジュセイ ユウドウヤク ILSMR ノ ソウセイ オ メザシテ
Title Alternative
The new method for the drug tolerance conquest : with the aim of the invention of inducer medicine of β-lactam drugs-susceptibility in methicillin-resistant Staphylococcus aureus (ILSMR)
Author
Higuti, Tomihiko Faculty of Pharmaceutical Sciences, The University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
β-lactam drugs-susceptibility
methicillin-resistant Staphylococcus aureus
ILSMR
penicillin binding protein
PBP 2’
Content Type
Journal Article
Description
Here we demonstrated that flavone and its derivatives had no or week antibacterial effect on methicillin-resistant Staphylococcus aureus (MRSA), but dramatically induced susceptibility to β-lactam antibiotics in most strains of MRSA isolated clinically, even up to a 32,000-fold increase. We named these flavones “inducer of β-lactam drugs-susceptibility in MRSA”, abbreviated as “ILSMR”. We also proposed the model for the mechanism of high resistance of MRSA to β-lactam drugs in which we assumed as follows : ( 1 ) PBP2’ (PBP2A) has low affinity not only to the β-lactam ring in β-lactam drugs, but also to D-Ala-(D)-Ala in N-acetyl-muramyl-pentapeptide and that ( 2 ) PBP 2’ can cross-link between N-acetyl-muramyl-pentapeptide and penta-glycine only when MRSA has been mutated such as the concentrations of these substrates have been greatly increased in the cross wall of staphylococcal cell. Based on the model, we could explain that ILSMRs increased susceptibility to β-lactam drugs in MRSA by decreasing the concentration of N-acetyl-muramyl-pentapeptide and/or penta-glycine in the growing cross wall. In such conditions, only normal PBP1~4 could work for the cross-link. This could be the reason why ILSMRs increased the susceptibility to β-lactam drugs in MRSA. We also found that flavone and its derivatives were highly active against systemic infections by MRSA in mice.
Journal Title
四国医学雑誌
ISSN
00373699
NCID
AN00102041
Publisher
徳島医学会
Volume
58
Issue
3
Start Page
107
End Page
121
Sort Key
107
Published Date
2002-06-15
EDB ID
FullText File
language
jpn
TextVersion
Publisher
departments
Pharmaceutical Sciences