Estimating the transfer rates of bacterial plasmids with an adapted Luria-Delbrück fluctuation analysis.
To increase our basic understanding of the ecology and evolution of conjugative plasmids, we need reliable estimates of their rate of transfer between bacterial cells. Current assays to measure transfer rate are based on deterministic modeling frameworks. However, some cell numbers in these assays c...
Main Authors: | , , , , , , |
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2022-07-01
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Series: | PLoS Biology |
Online Access: | https://doi.org/10.1371/journal.pbio.3001732 |
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author | Olivia Kosterlitz Adamaris Muñiz Tirado Claire Wate Clint Elg Ivana Bozic Eva M Top Benjamin Kerr |
author_facet | Olivia Kosterlitz Adamaris Muñiz Tirado Claire Wate Clint Elg Ivana Bozic Eva M Top Benjamin Kerr |
author_sort | Olivia Kosterlitz |
collection | DOAJ |
description | To increase our basic understanding of the ecology and evolution of conjugative plasmids, we need reliable estimates of their rate of transfer between bacterial cells. Current assays to measure transfer rate are based on deterministic modeling frameworks. However, some cell numbers in these assays can be very small, making estimates that rely on these numbers prone to noise. Here, we take a different approach to estimate plasmid transfer rate, which explicitly embraces this noise. Inspired by the classic fluctuation analysis of Luria and Delbrück, our method is grounded in a stochastic modeling framework. In addition to capturing the random nature of plasmid conjugation, our new methodology, the Luria-Delbrück method ("LDM"), can be used on a diverse set of bacterial systems, including cases for which current approaches are inaccurate. A notable example involves plasmid transfer between different strains or species where the rate that one type of cell donates the plasmid is not equal to the rate at which the other cell type donates. Asymmetry in these rates has the potential to bias or constrain current transfer estimates, thereby limiting our capabilities for estimating transfer in microbial communities. In contrast, the LDM overcomes obstacles of traditional methods by avoiding restrictive assumptions about growth and transfer rates for each population within the assay. Using stochastic simulations and experiments, we show that the LDM has high accuracy and precision for estimation of transfer rates compared to the most widely used methods, which can produce estimates that differ from the LDM estimate by orders of magnitude. |
first_indexed | 2024-04-13T02:14:43Z |
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issn | 1544-9173 1545-7885 |
language | English |
last_indexed | 2024-04-13T02:14:43Z |
publishDate | 2022-07-01 |
publisher | Public Library of Science (PLoS) |
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spelling | doaj.art-3a244c6ebc034116803fb3af710dd5d52022-12-22T03:07:12ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-07-01207e300173210.1371/journal.pbio.3001732Estimating the transfer rates of bacterial plasmids with an adapted Luria-Delbrück fluctuation analysis.Olivia KosterlitzAdamaris Muñiz TiradoClaire WateClint ElgIvana BozicEva M TopBenjamin KerrTo increase our basic understanding of the ecology and evolution of conjugative plasmids, we need reliable estimates of their rate of transfer between bacterial cells. Current assays to measure transfer rate are based on deterministic modeling frameworks. However, some cell numbers in these assays can be very small, making estimates that rely on these numbers prone to noise. Here, we take a different approach to estimate plasmid transfer rate, which explicitly embraces this noise. Inspired by the classic fluctuation analysis of Luria and Delbrück, our method is grounded in a stochastic modeling framework. In addition to capturing the random nature of plasmid conjugation, our new methodology, the Luria-Delbrück method ("LDM"), can be used on a diverse set of bacterial systems, including cases for which current approaches are inaccurate. A notable example involves plasmid transfer between different strains or species where the rate that one type of cell donates the plasmid is not equal to the rate at which the other cell type donates. Asymmetry in these rates has the potential to bias or constrain current transfer estimates, thereby limiting our capabilities for estimating transfer in microbial communities. In contrast, the LDM overcomes obstacles of traditional methods by avoiding restrictive assumptions about growth and transfer rates for each population within the assay. Using stochastic simulations and experiments, we show that the LDM has high accuracy and precision for estimation of transfer rates compared to the most widely used methods, which can produce estimates that differ from the LDM estimate by orders of magnitude.https://doi.org/10.1371/journal.pbio.3001732 |
spellingShingle | Olivia Kosterlitz Adamaris Muñiz Tirado Claire Wate Clint Elg Ivana Bozic Eva M Top Benjamin Kerr Estimating the transfer rates of bacterial plasmids with an adapted Luria-Delbrück fluctuation analysis. PLoS Biology |
title | Estimating the transfer rates of bacterial plasmids with an adapted Luria-Delbrück fluctuation analysis. |
title_full | Estimating the transfer rates of bacterial plasmids with an adapted Luria-Delbrück fluctuation analysis. |
title_fullStr | Estimating the transfer rates of bacterial plasmids with an adapted Luria-Delbrück fluctuation analysis. |
title_full_unstemmed | Estimating the transfer rates of bacterial plasmids with an adapted Luria-Delbrück fluctuation analysis. |
title_short | Estimating the transfer rates of bacterial plasmids with an adapted Luria-Delbrück fluctuation analysis. |
title_sort | estimating the transfer rates of bacterial plasmids with an adapted luria delbruck fluctuation analysis |
url | https://doi.org/10.1371/journal.pbio.3001732 |
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