2006 Fiscal Year Final Research Report Summary
Analysis of the efflux pump systems in the multidrug resistance of Haemophilus influenzae
| Project/Area Number |
16590375
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Bacteriology (including Mycology)
|
|---|
| Research Institution | Kyoto Pharmaceutical University |
|---|
Principal Investigator |
NISHINO Takeshi Kyoto Pharmaceutical University, Department of Microbiology, Professor, President, 薬学部, 教授 (50097838)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
GOTOH Naomasa Kyoto Pharmaceutical University, Department of Microbiology, Professor, 薬学部, 教授 (30121560)
OTSUKI Masako Kyoto Pharmaceutical University, Department of Microbiology, Assistant, 薬学部, 助手 (30121552)
|
|---|
| Project Period (FY) |
2004 – 2006
|
| Keywords | Haemophilus influenzae / Multidrug resistance / Efflux pump systems / Specific antibody to AcrAB / AcrAB overproducing strains / Macrolide antibiotics / Quinolones / β-lactam antibiotics |
|---|
| Research Abstract |
Bacterial antimicrobial efflux transporters have generally been grouped into four superfamilies, primary on the basis amino acid sequence homology. These include the major facilitator superfamily (MFS), the ATP-binding cassette family, the resistance-nodulation division (RND) family, and the small multidrug resistance (SMR) protein family. Recently, a fith family, referred to as the multidrug and toxic compound extrusion (MATE) family, has been identified. RND family transporters are unique to gram-negative bacteria and typically work in conjunction with a periplasmic membrane fusion protein (MFP) and an outer membrane protein. To successfully fight the increasing numbers of drug-resistant and multidrug-resistant(MDR) bacteria, extensive knowledge of the molecular mechanisms underlying microbial antibiotic resistance is required.
In this study, we tried to analysis the efflux pump systems in multidrug resistant Haemophilus influenzae. The genome sequencing of H.influenzae has identified a three-genome complex that is homologous to the acr AB cluster of E.coli. We identified HI 1462 protein as the outer membrane protein of AcrAB system of H. influenzae by computer analysis of whole genome. And we got HI1462 disrupted mutant by inserting the kanamycin resistance cartridge into HI1462 gene. We also got HI0894-and HI0895-(AcrAB) deletion mutants of H influenzae. We made the antibody against AcrAB and HI1462 proteins to analysis the role of efflux pump systems in multidrug resistant H.influenzae. Our study showed that AcrAB system is normally expressed in H.influenzae standard strain and also wild-type strains. The expression of this efflux system in H. influenzae produced only a small increase in the MIC because of having Omp2 porin, which produces large, highly permeable channels.
|
