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Data from: More evolvable bacteriophages better suppress their host

Cite this dataset

Meyer, Justin (2024). Data from: More evolvable bacteriophages better suppress their host [Dataset]. Dryad. https://doi.org/10.5061/dryad.tmpg4f56w

Abstract

The number of multidrug-resistant strains of bacteria is increasing rapidly, while the number of new antibiotic discoveries has stagnated. This trend has caused a surge in interest in bacteriophages as anti-bacterial therapeutics, in part because there is near limitless diversity of phages to harness. While this diversity provides an opportunity, it also creates the dilemma of having to decide which criteria to use to select phages. Here we test whether a phage’s ability to coevolve with its host (evolvability) should be considered and how this property compares to two previously proposed criteria: fast reproduction and thermostability. To do this, we compared the suppressiveness of three phages that vary by a single amino acid yet differ in these traits such that each strain maximized two of three characteristics. Our studies revealed that both evolvability and reproductive rate are independently important. The phage most able to suppress bacterial populations was the strain with high evolvability and reproductive rate, yet this phage was unstable. Phages varied due to differences in the types of resistance evolved against them and their ability to counteract resistance. When conditions were shifted to exaggerate the importance of thermostability, one of the stable phages was most suppressive in the short-term, but not over the long-term. Our results demonstrate the utility of biological therapeutics’ capacities to evolve and adjust in action to resolve complications like resistance evolution. Furthermore, evolvability is a property that can be engineered into phage therapeutics to enhance their effectiveness.

README: Data from: More evolvable bacteriophages better suppress their host

https://doi.org/10.5061/dryad.tmpg4f56w

The majority of the data are derived from measuring phage and bacterial population dynamics through enumerating densities over time via direct colony or plaque counts. There are a few exceptions. Figure 1 data was previously published (see link in 'Sharing/Access information' section and Table S1). Figure 3D data are frequencies of different colony morphologies enumerated by counting colonies of different phenotypes on indicator plates. Figure S4 is of growth rates which are based on counting density changes of plaque forming units over time.  

Description of the data and file structure

Bacterial titers reported in Figure 2  are phage titers for Figure S1 are provided in a single file '(080121)Figure2-counts(FINAL).csv'. Bacterial and phage densities are provided in a column 'Titers', which are computed through multiplying the adjacent three columns 'dilution counted', 'plating factor', and '#colonies/plaques'. The other columns provide details on the date the data were collected, the day of the suppression experiment in which the microbial samples were isolated, whether bacteria or phage were plated, and which replicate the values were from. 'NA' indicates missing data, the day '0' densities were estimated from a dilution of a phage stock and are provided in Table S2. 

The no-phage or wild type bacterial control was run at a separate time upon a reviewers request, so this data are provided in a separate file 'Fig2A*WT*Ctrl_JH.csv'. Here only the density calculations are provided, rows indicate reps, and columns indicate the time in which the samples were taken in terms of days. 

Figure 3 data are provided in 'Fig3_Data_JH'. Plaque forming units are provided for three separate phages ('C' stable, evolvable', 'L' fast-evolvable. 'R' stable, fast) on bacterial lawns created from 6 different different bacterial isolates (1 from each replicate of Figure 2 replicate populations) from days 1, 2, and 3. Figure 3D data are provided as well, these were calculations of the frequencies of different bacterial colony morphologies (proportion red). These were computed from the 'Raw Data for Proportions' columns 'White' and 'Red', their colony colors. 'All white' means only the white morphology was observed. The 'Plate' column indicates the type of tetrazolium indicator plate where the colonies were observed. 'Sample' indicates the phage the bacteria were co-cultured with (C, L, and R) and replicate number (1-6).

Data for Figure 4 and Figure S3 are provided in '(010722)Figure4-counts(FINAL).csv' and follow the same format as '(080121)Figure2-counts(FINAL).csv'.

Data for Figure 5 and Figure S4 are provided in '(030922)Figure5-counts(FINAL).csv' and follow the same format as '(080121)Figure2-counts(FINAL).csv'.

Growth rates provided in Figure S4 are provided in 'Figure S4 L,LOmpf,C,COmpf_Growthrates.csv'. Three replicate measurements (rows) for four different phages (columns). 

Sharing/Access information

Data for the first figure was derived from the following source. Please note though, the actual values were re-reported in Table S1 of 'More evolvable bacteriophages better suppress their host'. 

Code/Software

R 2020 version was used for graphing and statistics, AlphaFold was used to predict the J protein structure, and Chimera to create Figure 1.  

Methods

Most data were gained through basic microbiology techniques: colony counts on agar plates, plaque forming units on soft agar pverlay plates, and genotype identification on indicator plates.

Funding

Howard Hughes Medical Institute, Emerging Pathogens Initiative