Efflux pump overexpression in conjunction with alternation of outer membrane protein may induce Acinetobacter
LiuLin Luo1, XiaoFei Jiang, Qiong Wu
1Department of Clinical Laboratory, Renji Hospital, School of Medicine, Shanghai, China.
Background:
To investigate the role of outer membrane proteins in Acinetobacter baumannii resistant to imipenem, 2 strains were procured from the same patient.
Methods:
The imipenem-resistant strain was obtained following a period of imipenem treatment in vivo. The multilocus sequence typing and repetitive extragenic palindromic PCR results indicated that the imipenem-resistant strain originated from the sensitive one.
Results:
Isoelectric focusing detected no carbapenemases, with neither OXA carbapenemases nor metallo-β-lactamases found. Mass spectrophotometric analysis revealed that 3 outer membrane proteins were expressed differentially in the 2 strains: 2 downregulated proteins (OprD and CarO) and 1 upregulated the 34-kDa efflux pump protein in the resistant strain. A 32-fold decrease in the MIC for imipenem in the presence of Phe-Arg-β-naphthylamide in the same strain indicated a possible involvement of the efflux pump mechanism in its resistance, which was consistent with the findings that the mRNA expression of the 34-kDa efflux pump gene was almost fivefold upregulated in the imipenem-resistant strain compared with that in the imipenem-sensitive strain. Such a significant difference, however, was not found in the expression of AdeB and AdeJ between the 2 strains, and AdeE was not detected.
Conclusions:
Our results suggested that downregulation of outer membrane proteins in conjunction with efflux pump overexpression might contribute to imipenem resistance induced in vivo in A. baumannii.
Insights
Outer membrane protein downregulation and efflux pump overexpression contribute to imipenem resistance in Acinetobacter baumannii. This study investigated these mechanisms in resistant strains.
Area of Science:
- Microbiology
- Molecular Biology
- Drug Resistance
Background:
- Investigating mechanisms of imipenem resistance in Acinetobacter baumannii.
- Examining the role of outer membrane proteins in antibiotic resistance.
Purpose of the Study:
- To elucidate the contribution of outer membrane proteins and efflux pumps to imipenem resistance in Acinetobacter baumannii.
- To compare protein expression profiles between imipenem-sensitive and resistant strains.
Main Methods:
- Procurement of imipenem-sensitive and resistant Acinetobacter baumannii strains from the same patient.
- Utilizing multilocus sequence typing and repetitive extragenic palindromic PCR for strain characterization.
- Employing isoelectric focusing, mass spectrophotometry, and mRNA expression analysis to identify differentially expressed proteins and genes.
Main Results:
- No carbapenemases (OXA or metallo-β-lactamases) were detected.
- Downregulation of outer membrane proteins OprD and CarO, and upregulation of a 34-kDa efflux pump protein in the resistant strain.
- Evidence suggests efflux pump involvement in imipenem resistance, supported by decreased minimum inhibitory concentration (MIC) in the presence of an inhibitor and increased mRNA expression of the efflux pump gene.
Conclusions:
- Outer membrane protein downregulation and efflux pump overexpression are suggested mechanisms for in vivo induced imipenem resistance in Acinetobacter baumannii.
- Efflux pump activity plays a significant role in the development of carbapenem resistance.
Related Concept Videos
Development of Antibiotic Resistance
Mechanism of Antibiotic Resistance in MRSA
Antibiotic Selection
Gene Regulation in Microbial Communities: Quorum Sensing
Carrier-Mediated Transport
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...

