دورية أكاديمية
أعرض في EDS

Evolutionary action of mutations reveals antimicrobial resistance genes in Escherichia coli.

التفاصيل البيبلوغرافية
العنوان: Evolutionary action of mutations reveals antimicrobial resistance genes in Escherichia coli.
المؤلفون: Marciano DC; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. david.marciano@bcm.edu., Wang C; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Hsu TK; The Verna and Marrs McLean Department of Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA., Bourquard T; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Atri B; Structural and Computational Biology & Molecular Biophysics Program, Baylor College of Medicine, Houston, TX, 77030, USA.; Clara Analytics Inc., 451 El Camino Real #201, Santa Clara, CA, 95050, USA., Nehring RB; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.; The Verna and Marrs McLean Department of Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, 77030, USA.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA., Abel NS; Department of Pharmacology, Baylor College of Medicine, Houston, TX, 77030, USA., Bowling EA; The Verna and Marrs McLean Department of Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA., Chen TJ; Integrative Molecular & Biomedical Biosciences Program, Baylor College of Medicine, Houston, TX, 77030, USA., Lurie PD; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Katsonis P; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Rosenberg SM; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.; The Verna and Marrs McLean Department of Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, 77030, USA.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.; Integrative Molecular & Biomedical Biosciences Program, Baylor College of Medicine, Houston, TX, 77030, USA., Herman C; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, 77030, USA.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA., Lichtarge O; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. lichtarge@bcm.edu.; Structural and Computational Biology & Molecular Biophysics Program, Baylor College of Medicine, Houston, TX, 77030, USA. lichtarge@bcm.edu.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA. lichtarge@bcm.edu.; Computational and Integrative Biomedical Research Center, Baylor College of Medicine, Houston, TX, 77030, USA. lichtarge@bcm.edu.
المصدر: Nature communications [Nat Commun] 2022 Jun 09; Vol. 13 (1), pp. 3189. Date of Electronic Publication: 2022 Jun 09.
نوع المنشور: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Anti-Bacterial Agents*/pharmacology , Drug Resistance, Bacterial*/genetics , Escherichia coli*/drug effects , Escherichia coli*/genetics , Escherichia coli Proteins*/genetics, Ciprofloxacin/pharmacology ; Colistin/pharmacology ; Microbial Sensitivity Tests ; Mutation
مستخلص: Since antibiotic development lags, we search for potential drug targets through directed evolution experiments. A challenge is that many resistance genes hide in a noisy mutational background as mutator clones emerge in the adaptive population. Here, to overcome this noise, we quantify the impact of mutations through evolutionary action (EA). After sequencing ciprofloxacin or colistin resistance strains grown under different mutational regimes, we find that an elevated sum of the evolutionary action of mutations in a gene identifies known resistance drivers. This EA integration approach also suggests new antibiotic resistance genes which are then shown to provide a fitness advantage in competition experiments. Moreover, EA integration analysis of clinical and environmental isolates of antibiotic resistant of E. coli identifies gene drivers of resistance where a standard approach fails. Together these results inform the genetic basis of de novo colistin resistance and support the robust discovery of phenotype-driving genes via the evolutionary action of genetic perturbations in fitness landscapes.
(© 2022. The Author(s).)
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معلومات مُعتمدة: R01 CA250905 United States CA NCI NIH HHS; U01 AG068214 United States AG NIA NIH HHS; R01 AG061105 United States AG NIA NIH HHS; DP1 AG072751 United States AG NIA NIH HHS; R35 GM122598 United States GM NIGMS NIH HHS; DP1 AI152073 United States AI NIAID NIH HHS; R01 GM066099 United States GM NIGMS NIH HHS; R01 AG074009 United States AG NIA NIH HHS
المشرفين على المادة: 0 (Anti-Bacterial Agents)
0 (Escherichia coli Proteins)
5E8K9I0O4U (Ciprofloxacin)
Z67X93HJG1 (Colistin)
تواريخ الأحداث: Date Created: 20220610 Date Completed: 20220613 Latest Revision: 20240515
رمز التحديث: 20240515
مُعرف محوري في PubMed: PMC9184624
DOI: 10.1038/s41467-022-30889-1
PMID: 35680894
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-022-30889-1