ABC proteins and antibiotic drug resistance: is it all about transport?
I D Kerr1, E D Reynolds, J H Cove
1School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK. ian.kerr@nottingham.ac.uk
Abstract:
The precise mechanism of antibiotic-resistance-conferring ABC (ATP-binding-cassette) proteins (termed NBD2) remains open to debate. Currently, two hypotheses are recognized. In one, the NBD2 proteins are envisaged to act at the ribosome to impair antibiotic access to the target site on the 23 S rRNA. In the other, NBD2 proteins are believed to act as the components of ATP driven efflux pumps by associating with membrane spanning proteins capable of binding and transporting antibiotics. Pertinent data in support of these two hypotheses are discussed in this paper.
Insights
Antibiotic-resistance ABC proteins (NBD2) may work by blocking antibiotics at the ribosome or by pumping them out of the cell. This paper reviews evidence for both proposed mechanisms of NBD2 action.
Area of Science:
- Biochemistry
- Molecular Biology
- Microbiology
Background:
- ATP-binding-cassette (ABC) proteins, specifically NBD2, are implicated in conferring antibiotic resistance.
- The exact molecular mechanism by which NBD2 proteins confer resistance is not fully understood.
- Two primary hypotheses exist regarding NBD2 function in antibiotic resistance.
Purpose of the Study:
- To critically evaluate the existing hypotheses on the mechanism of antibiotic-resistance-conferring ABC proteins (NBD2).
- To discuss pertinent data supporting each proposed model of NBD2 action.
Main Methods:
- Literature review and critical analysis of existing data.
- Comparative discussion of two major hypotheses regarding NBD2 function.
Main Results:
- Hypothesis 1: NBD2 proteins interfere with antibiotic binding to the 23 S rRNA at the ribosome.
- Hypothesis 2: NBD2 proteins function as part of ATP-driven efflux pumps, working with membrane proteins to transport antibiotics.
Conclusions:
- The precise role of NBD2 in antibiotic resistance requires further elucidation.
- Evidence supporting both ribosomal inhibition and efflux pump mechanisms is presented for discussion.
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