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Efflux-mediated antimicrobial resistance
Abstract
Antibiotic resistance continues to plague antimicrobial chemotherapy of infectious disease. And while true biocide resistance is as yet unrealized, in vitro and in vivo episodes of reduced biocide susceptibility are common and the history of antibiotic resistance should not be ignored in the development and use of biocidal agents. Efflux mechanisms of resistance, both drug specific and multidrug, are important determinants of intrinsic and/or acquired resistance to these antimicrobials, with some accommodating both antibiotics and biocides. This latter raises the spectre (as yet generally unrealized) of biocide selection of multiple antibiotic-resistant organisms. Multidrug efflux mechanisms are broadly conserved in bacteria, are almost invariably chromosome-encoded and their expression in many instances results from mutations in regulatory genes. In contrast, drug-specific efflux mechanisms are generally encoded by plasmids and/or other mobile genetic elements (transposons, integrons) that carry additional resistance genes, and so their ready acquisition is compounded by their association with multidrug resistance. While there is some support for the latter efflux systems arising from efflux determinants of self-protection in antibiotic-producing Streptomyces spp. and, thus, intended as drug exporters, increasingly, chromosomal multidrug efflux determinants, at least in Gram-negative bacteria, appear not to be intended as drug exporters but as exporters with, perhaps, a variety of other roles in bacterial cells. Still, given the clinical significance of multidrug (and drug-specific) exporters, efflux must be considered in formulating strategies/approaches to treating drug-resistant infections, both in the development of new agents, for example, less impacted by efflux and in targeting efflux directly with efflux inhibitors.
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“The presence of multidrug efflux-related genes such as mexX, mexY and patB further supports the hypothesis that fluoride exposure may indirectly shape oral resistance by modulating bacterial stress response [58].”
From Severity-dependent alterations in oral microbiota and antibiotic resistance in children with dental fluorosis (2026) · cites this paper as [58]
In the citing paper
“Importantly, many of these pumps affect tetracycline and doxycycline, but do not decrease minocycline or tigecycline susceptibility, as they are not able to use these compounds as substrates (44, 47).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [44]
In the citing paper
“Finally, another predicted efflux pump is Lsa (encoded by the chromosomal gene lsa), which is responsible for the intrinsic resistance of E. faecalis to lincosamides and streptogramin A (LSA phenotype) (44, 45).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [44]
In the citing paper
“These systems may be substrate-specific (for a particular antibiotic such as tet determinants for tetracycline and mef genes for macrolides in pneumococci) or with broad substrate specificity, which are usually found in MDR bacteria (44).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [44]
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Self-citationAkkoç, N., Ghamat, A., & Akçelik, N. (2011) · International Journal of Dairy Technology · doi:10.1111/j.1471-0307.2011.00671.x · Cited by 25
Prosecká, J., Orlov, A. V., Fantin, Y. S., Зинченко, В. В., Babykin, M. M., & Tichý, M. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.07109.x · Cited by 25
Substituted dihydronaphthalenes as efflux pump inhibitors of Staphylococcus aureus
Thota, N., Reddy, M. V., Kumar, A., Khan, I. A., Sangwan, P. L., Kalia, N. P., Koul, J. L., & Koul, S. (2010) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2010.05.006 · Cited by 25
Johari, S. A., Mohtar, M., Suhaili, Z., Mazurah, M. I., Mustafa, S., & Ali, A. M. (2008) · Journal of Basic Microbiology · doi:10.1002/jobm.200700387 · Cited by 25
Kristensen, R., Andersen, J. B., Rybtke, M., Jansen, C. U., Fritz, B. G., Kiilerich, R. O., Uhd, J., Bjarnsholt, T., Qvortrup, K. M., Tolker‐Nielsen, T., et al. (2024) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01387-23 · Cited by 24
Efflux Pumps Represent Possible Evolutionary Convergence onto the β-Barrel Fold
Franklin, M. W., Nepomnyachiy, S., Feehan, R., Ben‐Tal, N., Kolodny, R., & Slusky, J. S. G. (2018) · Structure · doi:10.1016/j.str.2018.06.007 · Cited by 24
Afzal, M., Vijay, A. K., Stapleton, F. J., & Willcox, M. D. P. (2021) · Antibiotics · doi:10.3390/antibiotics10101203 · Cited by 28
A Review on Efflux Pump Inhibitors of Gram-Positive and Gram-Negative Bacteria from Plant Sources
Kumar, R., & Patial, S. J. P. (2016) · International Journal of Current Microbiology and Applied Sciences · doi:10.20546/ijcmas.2016.506.092 · Cited by 24
Serra, C., Bouharkat, B., Touil-Meddah, A. T., Guénin, S., & Mullié, C. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00366 · Cited by 24
Versatility of Stenotrophomonas maltophilia: Ecological roles of RND efflux pumps
Chauviat, A., Meyer, T., & Favre‐Bonté, S. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e14639 · Cited by 23
Metadata
- Authors
- Poole, K.
- Affiliations
- Queen's University (CA)
- Corresponding author
- Poole, Keith
- ORCID
- Poole, Keith
- Venue
- Journal of Antimicrobial Chemotherapy
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-05-24
- Volume
- 56
- Issue
- 1
- Pages
- 20-51
- ISSN
- 0305-7453 (ISSN-L)
- 1460-2091
- OpenAlex
- W2131256712
- Cited by
- 1,082
- References
- 733
- Citations by year
- 2026: 37 · 2025: 50 · 2024: 54 · 2023: 54 · 2022: 43 · 2021: 63 · 2020: 57 · 2019: 52 · 2018: 48 · 2017: 52 · 2016: 70 · 2015: 52 · 2014: 61 · 2013: 57 · 2012: 54
- FWCI
- 2.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Antimicrobial Chemotherapy (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (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
- efflux-mediated resistance, antimicrobial resistance, multidrug efflux pumps, biocide resistance, multidrug resistance, plasmid-encoded resistance genes, integrons, transposable elements, mobile genetic elements, efflux pump inhibitors, Gram-negative bacteria, intrinsic resistance, acquired resistance
- MeSH terms
- Aminoglycosides, Anti-Bacterial Agents, Biological Transport, Chloramphenicol, Tetracycline, Fluoroquinolones, Drug Resistance, Bacterial, Drug Resistance, Multiple, Bacterial
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