Journal
Elife
Publication Date
2021
Volume
10
First Page
e66657
Document Type
Open Access Publication
DOI
10.7554/eLife.66657
Rights and Permissions
eLife 2021;10:e66657 DOI: 10.7554/eLife.66657. © 2021, Miller et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Recommended Citation
Miller, Justin J.; Shah, Ishaan T.; Hatten, Jayda; Barekatain, Yasaman; Mueller, Elizabeth A.; Moustafa, Ahmed M.; Edwards, Rachel L.; Dowd, Cynthia S.; Planet, Paul J.; Muller, Florian L.; Jez, Joseph M.; and Odom John, Audrey R., "Structure-guided microbial targeting of antistaphylococcal prodrugs." Elife. 10, e66657 (2021).
https://digitalcommons.wustl.edu/open_access_pubs/10524
Figures and figure supplements.pdf (10182 kB)
elife-66657-transrepform-v2.docx (246 kB)
Transparent reporting form
elife-66657-video1.mp4 (973 kB)
In vivo activation rates depend on ester promoiety selection. Time series of fluorogenic ester substrate 1O activation. Substrate added at t = 10 min. Experiments were performed in biological duplicate.
elife-66657-video2.mp4 (498 kB)
In vivo activation rates depend on ester promoiety selection. Time series of fluorogenic ester substrate 3C activation. Substrate added at t = 10 min. Experiments were performed in biological duplicate.
elife-66657-video3.mp4 (630 kB)
In vivo activation rates depend on ester promoiety selection. Time series of fluorogenic ester substrate 5O activation. Substrate added at t = 10 min. Experiments were performed in biological duplicate.
elife-66657-video4.mp4 (478 kB)
In vivo activation rates depend on ester promoiety selection. Time series of fluorogenic ester substrate 9C activation. Substrate added at t = 10 min. Experiments were performed in biological duplicate.
elife-66657-fig2-data1-v2.xlsx (12 kB)
Figure 2—source data 1 S. aureus transposon mutants tested and POM-HEX sensitivity. Half-maximal inhibitory concentration (IC50) values for POM-HEX against predicted prodrug activating esterases. IC50 values are the result of three independent biological experiments with technical duplicates. p-values calculated as a one-way ANOVA with Dunnett’s correction for multiple comparisons.
elife-66657-fig2-data2-v2.xlsx (12 kB)
Figure 2—source data 2 S. aureus Newman resistant isolate SNPs and POM-HEX sensitivity. Genotype and phenotype of POM-HEX resistant S. aureus. Displayed are the whole-genome sequencing mutations that have been verified. Called mutations that were not observed via confirmatory Sanger sequencing are excluded. IC50 values are the result of three independent biologic replicates with technical duplicates.
elife-66657-fig2-data3-v2.xlsx (11 kB)
Figure 2—source data 3 S. aureus transposon mutants with genes identified by whole-genome sequencing and POM-HEX sensitivity. Half-maximal inhibitory concentration (IC50) values for POM-HEX against transposon mutations in genes identified by whole-genome sequencing. Assays performed in biological triplicate with technical duplicates. p-value calculated as a one-way ANOVA with Dunnett correction for multiple comparisons.
elife-66657-fig2-data4-v2.xlsx (9 kB)
Figure 2—source data 4 Accession numbers for the isolates used in WhatsGNU analysis.
elife-66657-fig3-data1-v2.xlsx (32 kB)
(1) Michaelis–Menten parameters for SaFrmB. Displayed are the results of three independent biological replicates in technical duplicate. (2) Michaelis–Menten parameters for SaGloB. Displayed are the results of three independent biological replicates in technical duplicate.
elife-66657-fig4-data1-v2.xlsx (9 kB)
Summary of crystallographic data collection and refinement statistics.
elife-66657-fig5-data1-v2.xlsx (9 kB)
Summary of crystallographic data collection and refinement statistics.
elife-66657-fig6-data1-v2.xlsx (21 kB)
(1) Michaelis–Menten parameters for human sera. Displayed are the results of three independent biological replicates in technical duplicate. (2) Michaelis–Menten parameters for mouse sera. Displayed are the results of three independent biological replicates in technical duplicate.
elife-66657-transrepform-v2.docx (246 kB)
Transparent reporting form
elife-66657-video1.mp4 (973 kB)
In vivo activation rates depend on ester promoiety selection. Time series of fluorogenic ester substrate 1O activation. Substrate added at t = 10 min. Experiments were performed in biological duplicate.
elife-66657-video2.mp4 (498 kB)
In vivo activation rates depend on ester promoiety selection. Time series of fluorogenic ester substrate 3C activation. Substrate added at t = 10 min. Experiments were performed in biological duplicate.
elife-66657-video3.mp4 (630 kB)
In vivo activation rates depend on ester promoiety selection. Time series of fluorogenic ester substrate 5O activation. Substrate added at t = 10 min. Experiments were performed in biological duplicate.
elife-66657-video4.mp4 (478 kB)
In vivo activation rates depend on ester promoiety selection. Time series of fluorogenic ester substrate 9C activation. Substrate added at t = 10 min. Experiments were performed in biological duplicate.
elife-66657-fig2-data1-v2.xlsx (12 kB)
Figure 2—source data 1 S. aureus transposon mutants tested and POM-HEX sensitivity. Half-maximal inhibitory concentration (IC50) values for POM-HEX against predicted prodrug activating esterases. IC50 values are the result of three independent biological experiments with technical duplicates. p-values calculated as a one-way ANOVA with Dunnett’s correction for multiple comparisons.
elife-66657-fig2-data2-v2.xlsx (12 kB)
Figure 2—source data 2 S. aureus Newman resistant isolate SNPs and POM-HEX sensitivity. Genotype and phenotype of POM-HEX resistant S. aureus. Displayed are the whole-genome sequencing mutations that have been verified. Called mutations that were not observed via confirmatory Sanger sequencing are excluded. IC50 values are the result of three independent biologic replicates with technical duplicates.
elife-66657-fig2-data3-v2.xlsx (11 kB)
Figure 2—source data 3 S. aureus transposon mutants with genes identified by whole-genome sequencing and POM-HEX sensitivity. Half-maximal inhibitory concentration (IC50) values for POM-HEX against transposon mutations in genes identified by whole-genome sequencing. Assays performed in biological triplicate with technical duplicates. p-value calculated as a one-way ANOVA with Dunnett correction for multiple comparisons.
elife-66657-fig2-data4-v2.xlsx (9 kB)
Figure 2—source data 4 Accession numbers for the isolates used in WhatsGNU analysis.
elife-66657-fig3-data1-v2.xlsx (32 kB)
(1) Michaelis–Menten parameters for SaFrmB. Displayed are the results of three independent biological replicates in technical duplicate. (2) Michaelis–Menten parameters for SaGloB. Displayed are the results of three independent biological replicates in technical duplicate.
elife-66657-fig4-data1-v2.xlsx (9 kB)
Summary of crystallographic data collection and refinement statistics.
elife-66657-fig5-data1-v2.xlsx (9 kB)
Summary of crystallographic data collection and refinement statistics.
elife-66657-fig6-data1-v2.xlsx (21 kB)
(1) Michaelis–Menten parameters for human sera. Displayed are the results of three independent biological replicates in technical duplicate. (2) Michaelis–Menten parameters for mouse sera. Displayed are the results of three independent biological replicates in technical duplicate.
