Analysis of a Library of <i>Escherichia coli</i> Transporter Knockout Strains to Identify Transport Pathways of Antibiotics
Antibiotic resistance is a major global healthcare issue. Antibiotic compounds cross the bacterial cell membrane via membrane transporters, and a major mechanism of antibiotic resistance is through modification of the membrane transporters to increase the efflux or reduce the influx of antibiotics....
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
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| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/11/8/1129 |
| _version_ | 1827600971682807808 |
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| author | Lachlan Jake Munro Douglas B. Kell |
| author_facet | Lachlan Jake Munro Douglas B. Kell |
| author_sort | Lachlan Jake Munro |
| collection | DOAJ |
| description | Antibiotic resistance is a major global healthcare issue. Antibiotic compounds cross the bacterial cell membrane via membrane transporters, and a major mechanism of antibiotic resistance is through modification of the membrane transporters to increase the efflux or reduce the influx of antibiotics. Targeting these transporters is a potential avenue to combat antibiotic resistance. In this study, we used an automated screening pipeline to evaluate the growth of a library of 447 <i>Escherichia coli</i> transporter knockout strains exposed to sub-inhibitory concentrations of 18 diverse antimicrobials. We found numerous knockout strains that showed more resistant or sensitive phenotypes to specific antimicrobials, suggestive of transport pathways. We highlight several specific drug-transporter interactions that we identified and provide the full dataset, which will be a useful resource in further research on antimicrobial transport pathways. Overall, we determined that transporters are involved in modulating the efficacy of almost all the antimicrobial compounds tested and can, thus, play a major role in the development of antimicrobial resistance. |
| first_indexed | 2024-03-09T04:46:36Z |
| format | Article |
| id | doaj.art-20c3c98450af4397a1bb74b50bb6126a |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T04:46:36Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-20c3c98450af4397a1bb74b50bb6126a2023-12-03T13:15:05ZengMDPI AGAntibiotics2079-63822022-08-01118112910.3390/antibiotics11081129Analysis of a Library of <i>Escherichia coli</i> Transporter Knockout Strains to Identify Transport Pathways of AntibioticsLachlan Jake Munro0Douglas B. Kell1Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Lyngby, DenmarkNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Lyngby, DenmarkAntibiotic resistance is a major global healthcare issue. Antibiotic compounds cross the bacterial cell membrane via membrane transporters, and a major mechanism of antibiotic resistance is through modification of the membrane transporters to increase the efflux or reduce the influx of antibiotics. Targeting these transporters is a potential avenue to combat antibiotic resistance. In this study, we used an automated screening pipeline to evaluate the growth of a library of 447 <i>Escherichia coli</i> transporter knockout strains exposed to sub-inhibitory concentrations of 18 diverse antimicrobials. We found numerous knockout strains that showed more resistant or sensitive phenotypes to specific antimicrobials, suggestive of transport pathways. We highlight several specific drug-transporter interactions that we identified and provide the full dataset, which will be a useful resource in further research on antimicrobial transport pathways. Overall, we determined that transporters are involved in modulating the efficacy of almost all the antimicrobial compounds tested and can, thus, play a major role in the development of antimicrobial resistance.https://www.mdpi.com/2079-6382/11/8/1129transportersantibiotics<i>Escherichia coli</i> |
| spellingShingle | Lachlan Jake Munro Douglas B. Kell Analysis of a Library of <i>Escherichia coli</i> Transporter Knockout Strains to Identify Transport Pathways of Antibiotics Antibiotics transporters antibiotics <i>Escherichia coli</i> |
| title | Analysis of a Library of <i>Escherichia coli</i> Transporter Knockout Strains to Identify Transport Pathways of Antibiotics |
| title_full | Analysis of a Library of <i>Escherichia coli</i> Transporter Knockout Strains to Identify Transport Pathways of Antibiotics |
| title_fullStr | Analysis of a Library of <i>Escherichia coli</i> Transporter Knockout Strains to Identify Transport Pathways of Antibiotics |
| title_full_unstemmed | Analysis of a Library of <i>Escherichia coli</i> Transporter Knockout Strains to Identify Transport Pathways of Antibiotics |
| title_short | Analysis of a Library of <i>Escherichia coli</i> Transporter Knockout Strains to Identify Transport Pathways of Antibiotics |
| title_sort | analysis of a library of i escherichia coli i transporter knockout strains to identify transport pathways of antibiotics |
| topic | transporters antibiotics <i>Escherichia coli</i> |
| url | https://www.mdpi.com/2079-6382/11/8/1129 |
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