The role of population dynamics in driving bacterial persistence
Bacterial persister cells can survive a broad range of antibiotics despite being genetically susceptible. This trait is clinically relevant, yet evolutionary explanations for persistence remain mysterious. Significant focus has been given to single cell studies with the aim of identifying genes resp...
| מחבר ראשי: | |
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| מחברים אחרים: | |
| פורמט: | Thesis |
| שפה: | English |
| יצא לאור: |
2023
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| נושאים: |
| _version_ | 1826312991043223552 |
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| author | Davies, SEF |
| author2 | Griffin, A |
| author_facet | Griffin, A Davies, SEF |
| author_sort | Davies, SEF |
| collection | OXFORD |
| description | Bacterial persister cells can survive a broad range of antibiotics despite being genetically susceptible. This trait is clinically relevant, yet evolutionary explanations for persistence remain mysterious. Significant focus has been given to single cell studies with the aim of identifying genes responsible for persistence. However, other studies have indicated that persistence may not be genetically-driven at all but instead simply a by-product of other cellular processes. Moving away from the single cell approach, more needs to be done to consider persistence at the population level – strikingly, the proportion of persisters is maintained at a remarkably low level across populations and even species, between 0.0001-1%. Uncovering the conditions that promote persistence could tell us more about the regulatory mechanisms behind this trait. In my thesis, I explore the population-wide dynamics behind elevated levels of bacterial persistence in <em>Pseudomonas aeruginosa</em>. I first look at how changing bacterial population dynamics (growth rate and cell density) affect persistence by varying the culture inoculum density to detect the effect of growth, while also controlling for age of culture. This reveals inoculum density dependent effects where persistence peaks are not always associated with stationary phase as is commonly assumed in the literature, but perhaps with the number of divisions of individual cells. To expand this work, I replicate the study with, <em>Escherichia coli</em>, the most widely studied species in the persister research field. I find that <em>E. coli</em> displays different persistence patterns to <em>P. aeruginosa</em>, with limited inoculation density-dependent responses. While persistence patterns varied between species, extracellular ATP, which can be an indicator of cell lysis, was consistent with persistence patterns across both species, presenting intriguing avenues to explore in future. Lastly, I look at an unusual phenomenon I came across in my early work where I saw antibiotic-induced growth occurring in <em>P. aeruginosa</em> which I term a ‘stress divide’. Here, I look at potential links with another antibiotic survival mechanism: heteroresistance, a less understood survival trait whereby a bacterial subpopulation is heterogeneously resistant to the antibiotic treatment. This introduces the concept of looking at how heterogenous phenotypic traits such as persistence and heteroresistance could work synergistically to promote population survival. In summary, by testing a broad range of growth conditions, I have found that persistence is not always greatest in stationary phase, is species-specific, and can work in tandem with traits like heteroresistance to enhance survival. My thesis highlights the significance of examining the impact of population dynamics on persistence, considering the mechanisms driving persistence on a species-by-species basis. |
| first_indexed | 2024-09-25T04:05:37Z |
| format | Thesis |
| id | oxford-uuid:aa029e76-fb2c-4a8f-976f-c52213519c96 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:05:37Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | oxford-uuid:aa029e76-fb2c-4a8f-976f-c52213519c962024-05-20T09:07:09ZThe role of population dynamics in driving bacterial persistenceThesishttp://purl.org/coar/resource_type/c_db06uuid:aa029e76-fb2c-4a8f-976f-c52213519c96Drug resistance in microorganismsAntibioticsMicrobiologyBacteriaPseudomonas aeruginosaEvolutionEnglishHyrax Deposit2023Davies, SEFGriffin, AGhoul, MBacterial persister cells can survive a broad range of antibiotics despite being genetically susceptible. This trait is clinically relevant, yet evolutionary explanations for persistence remain mysterious. Significant focus has been given to single cell studies with the aim of identifying genes responsible for persistence. However, other studies have indicated that persistence may not be genetically-driven at all but instead simply a by-product of other cellular processes. Moving away from the single cell approach, more needs to be done to consider persistence at the population level – strikingly, the proportion of persisters is maintained at a remarkably low level across populations and even species, between 0.0001-1%. Uncovering the conditions that promote persistence could tell us more about the regulatory mechanisms behind this trait. In my thesis, I explore the population-wide dynamics behind elevated levels of bacterial persistence in <em>Pseudomonas aeruginosa</em>. I first look at how changing bacterial population dynamics (growth rate and cell density) affect persistence by varying the culture inoculum density to detect the effect of growth, while also controlling for age of culture. This reveals inoculum density dependent effects where persistence peaks are not always associated with stationary phase as is commonly assumed in the literature, but perhaps with the number of divisions of individual cells. To expand this work, I replicate the study with, <em>Escherichia coli</em>, the most widely studied species in the persister research field. I find that <em>E. coli</em> displays different persistence patterns to <em>P. aeruginosa</em>, with limited inoculation density-dependent responses. While persistence patterns varied between species, extracellular ATP, which can be an indicator of cell lysis, was consistent with persistence patterns across both species, presenting intriguing avenues to explore in future. Lastly, I look at an unusual phenomenon I came across in my early work where I saw antibiotic-induced growth occurring in <em>P. aeruginosa</em> which I term a ‘stress divide’. Here, I look at potential links with another antibiotic survival mechanism: heteroresistance, a less understood survival trait whereby a bacterial subpopulation is heterogeneously resistant to the antibiotic treatment. This introduces the concept of looking at how heterogenous phenotypic traits such as persistence and heteroresistance could work synergistically to promote population survival. In summary, by testing a broad range of growth conditions, I have found that persistence is not always greatest in stationary phase, is species-specific, and can work in tandem with traits like heteroresistance to enhance survival. My thesis highlights the significance of examining the impact of population dynamics on persistence, considering the mechanisms driving persistence on a species-by-species basis. |
| spellingShingle | Drug resistance in microorganisms Antibiotics Microbiology Bacteria Pseudomonas aeruginosa Evolution Davies, SEF The role of population dynamics in driving bacterial persistence |
| title | The role of population dynamics in driving bacterial persistence |
| title_full | The role of population dynamics in driving bacterial persistence |
| title_fullStr | The role of population dynamics in driving bacterial persistence |
| title_full_unstemmed | The role of population dynamics in driving bacterial persistence |
| title_short | The role of population dynamics in driving bacterial persistence |
| title_sort | role of population dynamics in driving bacterial persistence |
| topic | Drug resistance in microorganisms Antibiotics Microbiology Bacteria Pseudomonas aeruginosa Evolution |
| work_keys_str_mv | AT daviessef theroleofpopulationdynamicsindrivingbacterialpersistence AT daviessef roleofpopulationdynamicsindrivingbacterialpersistence |