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

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.

Related Concept Videos

ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
Development of Antibiotic Resistance01:30

Development of Antibiotic Resistance

Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
ABC Transporters: Importer01:27

ABC Transporters: Importer

ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Antibiotic Selection00:57

Antibiotic Selection

Overview
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...