دورية أكاديمية
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Crucial role for central carbon metabolism in the bacterial L-form switch and killing by β-lactam antibiotics.

التفاصيل البيبلوغرافية
العنوان: Crucial role for central carbon metabolism in the bacterial L-form switch and killing by β-lactam antibiotics.
المؤلفون: Kawai Y; Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle upon Tyne, UK. yoshikazu.kawai@ncl.ac.uk., Mercier R; Laboratoire de Chimie Bactérienne, UMR 7283, Institut de Microbiologie de la Méditerranée, CNRS-Aix-Marseille University, Marseille, France., Mickiewicz K; Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle upon Tyne, UK., Serafini A; Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, UK., Sório de Carvalho LP; Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, UK., Errington J; Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle upon Tyne, UK. jeff.errington@ncl.ac.uk.
المصدر: Nature microbiology [Nat Microbiol] 2019 Oct; Vol. 4 (10), pp. 1716-1726. Date of Electronic Publication: 2019 Jul 08.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101674869 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2058-5276 (Electronic) Linking ISSN: 20585276 NLM ISO Abbreviation: Nat Microbiol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Publishing Group, [2016]-
مواضيع طبية MeSH: Bacillus subtilis/*drug effects , Bacillus subtilis/*metabolism , Carbon/*metabolism , L Forms/*drug effects , L Forms/*metabolism , beta-Lactams/*pharmacology, Bacillus subtilis/genetics ; Bacillus subtilis/growth & development ; Cell Wall/drug effects ; Cell Wall/metabolism ; Electron Transport/genetics ; Enterococcus faecium/drug effects ; Enterococcus faecium/growth & development ; Enterococcus faecium/metabolism ; Gluconeogenesis ; L Forms/genetics ; L Forms/growth & development ; Muramidase/pharmacology ; Mutation ; Penicillin G/pharmacology ; Peptidoglycan/drug effects ; Peptidoglycan/metabolism ; Phosphoenolpyruvate Sugar Phosphotransferase System/genetics ; Reactive Oxygen Species/metabolism ; Reactive Oxygen Species/toxicity
مستخلص: The peptidoglycan cell wall is an essential structure for the growth of most bacteria. However, many are capable of switching into a wall-deficient L-form state in which they are resistant to antibiotics that target cell wall synthesis under osmoprotective conditions, including host environments. L-form cells may have an important role in chronic or recurrent infections. The cellular pathways involved in switching to and from the L-form state remain poorly understood. This work shows that the lack of a cell wall, or blocking its synthesis with β-lactam antibiotics, results in an increased flux through glycolysis. This leads to the production of reactive oxygen species from the respiratory chain, which prevents L-form growth. Compensating for the metabolic imbalance by slowing down glycolysis, activating gluconeogenesis or depleting oxygen enables L-form growth in Bacillus subtilis, Listeria monocytogenes and Staphylococcus aureus. These effects do not occur in Enterococcus faecium, which lacks the respiratory chain pathway. Our results collectively show that when cell wall synthesis is blocked under aerobic and glycolytic conditions, perturbation of cellular metabolism causes cell death. We provide a mechanistic framework for many anecdotal descriptions of the optimal conditions for L-form growth and non-lytic killing by β-lactam antibiotics.
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; 670980 International ERC_ European Research Council; FC001060 United Kingdom ARC_ Arthritis Research UK
المشرفين على المادة: 0 (Peptidoglycan)
0 (Reactive Oxygen Species)
0 (beta-Lactams)
7440-44-0 (Carbon)
EC 2.7.1.- (Phosphoenolpyruvate Sugar Phosphotransferase System)
EC 3.2.1.17 (Muramidase)
Q42T66VG0C (Penicillin G)
تواريخ الأحداث: Date Created: 20190710 Date Completed: 20200120 Latest Revision: 20240607
رمز التحديث: 20240607
مُعرف محوري في PubMed: PMC6755032
DOI: 10.1038/s41564-019-0497-3
PMID: 31285586
قاعدة البيانات: MEDLINE
الوصف
تدمد:2058-5276
DOI:10.1038/s41564-019-0497-3