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Updated: Feb 11, 2026

Single Cell Measurements of Vacuolar Rupture Caused by Intracellular Pathogens
Published on: June 12, 2013
Multiantibiotic resistance caused by active drug extrusion in hospital pathogens
Taiji Nakae1, Eisaku Yoshihara1, Hiroshi Yoneyama1
1The Department of Molecular Life Science, Tokai University School of Medicine, 259-11, Isehara, Japan.
Abstract:
All living organisms from bacteria to mammals extrude noxious compounds to the external medium. When exposed to antibiotics, bacteria actively extrude intracellular antibiotic and develop resistance to the drug. Nosocomial Staphylococcus aureaus, Pseudomonas aeruginosa and other bacteria are resistant to a broad range of antibiotics and to structurally and functionally diverse chemotherapeutic agents and disinfectants. For this reason nosocomial infections are especially hard to treat in immunocompromised patients who may be infected by low-virulence bacteria. Extrusion-related antibiotic resistance in P. aeruginosa arises by the expression of Mex-extrusion pumps, including genetically distinct mexA-mexB-oprM, mexC-mexD-oprj, and mexE-mexF-oprN systems, each encoding two inner membrane proteins and one outer membrane protein. S. aureus becomes resistant to fluoroquinolone by expressing NorA extrusion proteins and to disinfectants by expressing Qac extrusion proteins. The drug extrusion machinery may be classified into several categories according to the number of transmembrane segments it exhibits. The proteins that belong to a major facilitator super family have 12 or 14 transmembrane segments. The extrusion proteins with molecular weight of 12,000 to 15,000 span the membrane 4 times and are collectively called small multidrug resistance proteins. The extrusion proteins that transport substrate across the inner and outer membrane of gram-negative bacteria are in the resistance nodulation cell division family.
Insights
Bacteria develop antibiotic resistance by extruding drugs using specialized protein pumps. This extrusion mechanism, seen in pathogens like Staphylococcus aureus and Pseudomonas aeruginosa, contributes to difficult-to-treat nosocomial infections.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- All organisms, including bacteria, expel waste products.
- Antibiotic exposure triggers bacteria to extrude drugs, leading to resistance.
- Nosocomial infections caused by resistant bacteria like Staphylococcus aureus and Pseudomonas aeruginosa are challenging to treat, especially in immunocompromised individuals.
Purpose of the Study:
- To elucidate the mechanisms of drug extrusion in bacteria.
- To understand the role of extrusion pumps in antibiotic resistance.
- To classify bacterial drug extrusion machinery.
Main Methods:
- Analysis of gene expression for Mex-extrusion pumps in Pseudomonas aeruginosa.
- Identification of NorA and Qac extrusion proteins in Staphylococcus aureus.
- Classification of drug extrusion proteins based on transmembrane segments and molecular weight.
Main Results:
- Pseudomonas aeruginosa utilizes Mex-extrusion pump systems (mexA-mexB-oprM, mexC-mexD-oprj, mexE-mexF-oprN) for antibiotic resistance.
- Staphylococcus aureus employs NorA and Qac extrusion proteins for resistance to fluoroquinolones and disinfectants, respectively.
- Drug extrusion machinery can be categorized into major facilitator superfamily proteins, small multidrug resistance proteins, and resistance nodulation cell division family proteins.
Conclusions:
- Bacterial drug extrusion via specialized protein pumps is a significant mechanism for developing antibiotic resistance.
- Understanding these extrusion systems is crucial for combating nosocomial infections.
- The diverse nature of extrusion proteins highlights the complexity of bacterial defense mechanisms against antimicrobial agents.
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