Cited by 1,231Antibiotic Resistance in BacteriaDrug Transport and Resistance MechanismsBacterial Genetics and Biotechnology

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Clinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria

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Piddock, Laura J. V.·2006·Clinical Microbiology Reviews

DOI 10.1128/cmr.19.2.382-402.2006PMC PMC1471989

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Abstract

SUMMARY: Efflux pump genes and proteins are present in both antibiotic-susceptible and antibiotic-resistant bacteria. Pumps may be specific for one substrate or may transport a range of structurally dissimilar compounds (including antibiotics of multiple classes); such pumps can be associated with multiple drug (antibiotic) resistance (MDR). However, the clinical relevance of efflux-mediated resistance is species, drug, and infection dependent. This review focuses on chromosomally encoded pumps in bacteria that cause infections in humans. Recent structural data provide valuable insights into the mechanisms of drug transport. MDR efflux pumps contribute to antibiotic resistance in bacteria in several ways: (i) inherent resistance to an entire class of agents, (ii) inherent resistance to specific agents, and (iii) resistance conferred by overexpression of an efflux pump. Enhanced efflux can be mediated by mutations in (i) the local repressor gene, (ii) a global regulatory gene, (iii) the promoter region of the transporter gene, or (iv) insertion elements upstream of the transporter gene. Some data suggest that resistance nodulation division systems are important in pathogenicity and/or survival in a particular ecological niche. Inhibitors of various efflux pump systems have been described; typically these are plant alkaloids, but as yet no product has been marketed.

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Authors: Piddock, L. J. V.
Affiliations: University of Birmingham (GB)
Corresponding author: Piddock, Laura J. V.
ORCID: Piddock, Laura J. V.
Venue: Clinical Microbiology Reviews
Publisher: American Society for Microbiology
Published: 2006-04
Volume: 19
Issue: 2
Pages: 382-402
ISSN: 0893-8512 (ISSN-L)
1098-6618
DOI: 10.1128/cmr.19.2.382-402.2006
PMC: PMC1471989
OpenAlex: W2112586763
Cited by: 1,231
References: 242
Citations by year: 2026: 37 · 2025: 45 · 2024: 66 · 2023: 65 · 2022: 69 · 2021: 99 · 2020: 75 · 2019: 69 · 2018: 53 · 2017: 79 · 2016: 72 · 2015: 69 · 2014: 72 · 2013: 57 · 2012: 63
FWCI: 2.45
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Clinical Microbiology Reviews (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Topics: Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords: multidrug resistance, efflux pumps, antibiotic resistance, pathogenic bacteria, efflux pump regulation, efflux pump inhibitors, plant alkaloids, drug transport mechanisms, insertion elements
MeSH terms: Alkaloids, Anti-Infective Agents, Bacteria, Bacterial Proteins, Biological Transport, Chromosomes, Bacterial, Disinfectants, DNA Transposable Elements, Genes, Regulator, Mutation, Promoter Regions, Genetic, Virulence, Drug Resistance, Multiple, Bacterial, Membrane Transport Proteins, ATP-Binding Cassette, Sub-Family C Proteins

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Clinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria

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