The inoculum effect and band‐pass bacterial response to periodic antibiotic treatment
Abstract The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. To gain insight into this phenomenon...
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| Format: | Article |
| Language: | English |
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Springer Nature
2012-10-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2012.49 |
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| _version_ | 1849235641766772736 |
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| author | Cheemeng Tan Robert Phillip Smith Jaydeep K Srimani Katherine A Riccione Sameer Prasada Meta Kuehn Lingchong You |
| author_facet | Cheemeng Tan Robert Phillip Smith Jaydeep K Srimani Katherine A Riccione Sameer Prasada Meta Kuehn Lingchong You |
| author_sort | Cheemeng Tan |
| collection | DOAJ |
| description | Abstract The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. To gain insight into this phenomenon, we have analyzed responses of a lab strain of Escherichia coli to antibiotics that target the ribosome. We show that the IE can be explained by bistable inhibition of bacterial growth. A critical requirement for this bistability is sufficiently fast degradation of ribosomes, which can result from antibiotic‐induced heat‐shock response. Furthermore, antibiotics that elicit the IE can lead to ‘band‐pass’ response of bacterial growth to periodic antibiotic treatment: the treatment efficacy drastically diminishes at intermediate frequencies of treatment. Our proposed mechanism for the IE may be generally applicable to other bacterial species treated with antibiotics targeting the ribosomes. |
| format | Article |
| id | doaj-art-c268af2f8d35496ba40f6810a5285906 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2012-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-c268af2f8d35496ba40f6810a52859062025-08-20T04:02:44ZengSpringer NatureMolecular Systems Biology1744-42922012-10-018111110.1038/msb.2012.49The inoculum effect and band‐pass bacterial response to periodic antibiotic treatmentCheemeng Tan0Robert Phillip Smith1Jaydeep K Srimani2Katherine A Riccione3Sameer Prasada4Meta Kuehn5Lingchong You6Department of Biomedical Engineering, Duke UniversityDepartment of Biomedical Engineering, Duke UniversityDepartment of Biomedical Engineering, Duke UniversityDepartment of Biomedical Engineering, Duke UniversityDepartment of Biomedical Engineering, Duke UniversityDepartment of Biochemistry, Duke University Medical CenterDepartment of Biomedical Engineering, Duke UniversityAbstract The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. To gain insight into this phenomenon, we have analyzed responses of a lab strain of Escherichia coli to antibiotics that target the ribosome. We show that the IE can be explained by bistable inhibition of bacterial growth. A critical requirement for this bistability is sufficiently fast degradation of ribosomes, which can result from antibiotic‐induced heat‐shock response. Furthermore, antibiotics that elicit the IE can lead to ‘band‐pass’ response of bacterial growth to periodic antibiotic treatment: the treatment efficacy drastically diminishes at intermediate frequencies of treatment. Our proposed mechanism for the IE may be generally applicable to other bacterial species treated with antibiotics targeting the ribosomes.https://doi.org/10.1038/msb.2012.49antibioticbacteriabistabilityinoculum effect |
| spellingShingle | Cheemeng Tan Robert Phillip Smith Jaydeep K Srimani Katherine A Riccione Sameer Prasada Meta Kuehn Lingchong You The inoculum effect and band‐pass bacterial response to periodic antibiotic treatment Molecular Systems Biology antibiotic bacteria bistability inoculum effect |
| title | The inoculum effect and band‐pass bacterial response to periodic antibiotic treatment |
| title_full | The inoculum effect and band‐pass bacterial response to periodic antibiotic treatment |
| title_fullStr | The inoculum effect and band‐pass bacterial response to periodic antibiotic treatment |
| title_full_unstemmed | The inoculum effect and band‐pass bacterial response to periodic antibiotic treatment |
| title_short | The inoculum effect and band‐pass bacterial response to periodic antibiotic treatment |
| title_sort | inoculum effect and band pass bacterial response to periodic antibiotic treatment |
| topic | antibiotic bacteria bistability inoculum effect |
| url | https://doi.org/10.1038/msb.2012.49 |
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