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...

Full description

Bibliographic Details
Main Authors: Olivia Kosterlitz, Adamaris Muñiz Tirado, Claire Wate, Clint Elg, Ivana Bozic, Eva M Top, Benjamin Kerr
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-07-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.3001732
_version_ 1811283551517147136
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
format Article
id doaj.art-3a244c6ebc034116803fb3af710dd5d5
institution Directory Open Access Journal
issn 1544-9173
1545-7885
language English
last_indexed 2024-04-13T02:14:43Z
publishDate 2022-07-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Biology
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
work_keys_str_mv AT oliviakosterlitz estimatingthetransferratesofbacterialplasmidswithanadaptedluriadelbruckfluctuationanalysis
AT adamarismuniztirado estimatingthetransferratesofbacterialplasmidswithanadaptedluriadelbruckfluctuationanalysis
AT clairewate estimatingthetransferratesofbacterialplasmidswithanadaptedluriadelbruckfluctuationanalysis
AT clintelg estimatingthetransferratesofbacterialplasmidswithanadaptedluriadelbruckfluctuationanalysis
AT ivanabozic estimatingthetransferratesofbacterialplasmidswithanadaptedluriadelbruckfluctuationanalysis
AT evamtop estimatingthetransferratesofbacterialplasmidswithanadaptedluriadelbruckfluctuationanalysis
AT benjaminkerr estimatingthetransferratesofbacterialplasmidswithanadaptedluriadelbruckfluctuationanalysis