دورية أكاديمية

Phenotypic resistant single-cell characteristics under recurring ampicillin antibiotic exposure in Escherichia coli .

التفاصيل البيبلوغرافية
العنوان: Phenotypic resistant single-cell characteristics under recurring ampicillin antibiotic exposure in Escherichia coli .
المؤلفون: Kollerová S; Department of Biology, University of Southern Denmark, Odense, Denmark., Jouvet L; Department of Biology, University of Southern Denmark, Odense, Denmark., Smelková J; Department of Biology, University of Southern Denmark, Odense, Denmark., Zunk-Parras S; Biological Institute, Freie Universität Berlin, Berlin, Germany., Rodríguez-Rojas A; Biological Institute, Freie Universität Berlin, Berlin, Germany., Steiner UK; Department of Biology, University of Southern Denmark, Odense, Denmark.; Biological Institute, Freie Universität Berlin, Berlin, Germany.
المصدر: MSystems [mSystems] 2024 Jul 23; Vol. 9 (7), pp. e0025624. Date of Electronic Publication: 2024 Jun 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101680636 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2379-5077 (Electronic) Linking ISSN: 23795077 NLM ISO Abbreviation: mSystems Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Society for Microbiology, [2016]-
مواضيع طبية MeSH: Ampicillin*/pharmacology , Escherichia coli*/drug effects , Escherichia coli*/genetics , Anti-Bacterial Agents*/pharmacology , Phenotype* , Drug Resistance, Bacterial*/genetics , Drug Resistance, Bacterial*/drug effects , Single-Cell Analysis*, Microbial Sensitivity Tests
مستخلص: Non-heritable, phenotypic drug resistance toward antibiotics challenges antibiotic therapies. Characteristics of such phenotypic resistance have implications for the evolution of heritable resistance. Diverse forms of phenotypic resistance have been described, but phenotypic resistance characteristics remain less explored than genetic resistance. Here, we add novel combinations of single-cell characteristics of phenotypic resistant E. coli cells and compare those to characteristics of susceptible cells of the parental population by exposure to different levels of recurrent ampicillin antibiotic. Contrasting expectations, we did not find commonly described characteristics of phenotypic resistant cells that arrest growth or near growth. We find that under ampicillin exposure, phenotypic resistant cells reduced their growth rate by about 50% compared to growth rates prior to antibiotic exposure. The growth reduction is a delayed alteration to antibiotic exposure, suggesting an induced response and not a stochastic switch or caused by a predetermined state as frequently described. Phenotypic resistant cells exhibiting constant slowed growth survived best under ampicillin exposure and, contrary to expectations, not only fast-growing cells suffered high mortality triggered by ampicillin but also growth-arrested cells. Our findings support diverse modes of phenotypic resistance, and we revealed resistant cell characteristics that have been associated with enhanced genetically fixed resistance evolution, which supports claims of an underappreciated role of phenotypic resistant cells toward genetic resistance evolution. A better understanding of phenotypic resistance will benefit combatting genetic resistance by developing and engulfing effective anti-phenotypic resistance strategies.
Importance: Antibiotic resistance is a major challenge for modern medicine. Aside from genetic resistance to antibiotics, phenotypic resistance that is not heritable might play a crucial role for the evolution of antibiotic resistance. Using a highly controlled microfluidic system, we characterize single cells under recurrent exposure to antibiotics. Fluctuating antibiotic exposure is likely experienced under common antibiotic therapies. These phenotypic resistant cell characteristics differ from previously described phenotypic resistance, highlighting the diversity of modes of resistance. The phenotypic characteristics of resistant cells we identify also imply that such cells might provide a stepping stone toward genetic resistance, thereby causing treatment failure.
Competing Interests: The authors declare no conflict of interest.
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معلومات مُعتمدة: 430170797 Deutsche Forschungsgemeinschaft (DFG); 430174701 Deutsche Forschungsgemeinschaft (DFG)
فهرسة مساهمة: Keywords: antibiotic resistance; microfluidics; persistence; phenotypic resistance; single-cell; tolerance; β-lactam antibiotics
المشرفين على المادة: 7C782967RD (Ampicillin)
0 (Anti-Bacterial Agents)
تواريخ الأحداث: Date Created: 20240626 Date Completed: 20240723 Latest Revision: 20240725
رمز التحديث: 20240726
مُعرف محوري في PubMed: PMC11264686
DOI: 10.1128/msystems.00256-24
PMID: 38920373
قاعدة البيانات: MEDLINE
الوصف
تدمد:2379-5077
DOI:10.1128/msystems.00256-24