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4-Hydroxy-2-nonenal antimicrobial toxicity is neutralized by an intracellular pathogen

التفاصيل البيبلوغرافية
العنوان: 4-Hydroxy-2-nonenal antimicrobial toxicity is neutralized by an intracellular pathogen
المؤلفون: Hannah Tabakh, Adelle P McFarland, Maureen K Thomason, Alex J Pollock, Rochelle C Glover, Shivam A Zaver, Joshua J Woodward
المصدر: eLife, Vol 10 (2021)
بيانات النشر: eLife Sciences Publications Ltd, 2021.
سنة النشر: 2021
المجموعة: LCC:Medicine
LCC:Science
LCC:Biology (General)
مصطلحات موضوعية: Listeria monocytogenes, 4-HNE, reactive oxygen species, bacterial pathogenesis, Medicine, Science, Biology (General), QH301-705.5
الوصف: Pathogens encounter numerous antimicrobial responses during infection, including the reactive oxygen species (ROS) burst. ROS-mediated oxidation of host membrane poly-unsaturated fatty acids (PUFAs) generates the toxic alpha-beta carbonyl 4-hydroxy-2-nonenal (4-HNE). Although studied extensively in the context of sterile inflammation, research into 4-HNE’s role during infection remains limited. Here, we found that 4-HNE is generated during bacterial infection, that it impacts growth and survival in a range of bacteria, and that the intracellular pathogen Listeria monocytogenes induces many genes in response to 4-HNE exposure. A component of the L. monocytogenes 4-HNE response is the expression of the genes lmo0103 and lmo0613, deemed rha1 and rha2 (reductase of host alkenals), respectively, which code for two NADPH-dependent oxidoreductases that convert 4-HNE to the product 4-hydroxynonanal (4-HNA). Loss of these genes had no impact on L. monocytogenes bacterial burdens during murine or tissue culture infection. However, heterologous expression of rha1/2 in Bacillus subtilis significantly increased bacterial resistance to 4-HNE in vitro and promoted bacterial survival following phagocytosis by murine macrophages in an ROS-dependent manner. Thus, Rha1 and Rha2 are not necessary for 4-HNE resistance in L. monocytogenes but are sufficient to confer resistance to an otherwise sensitive organism in vitro and in host cells. Our work demonstrates that 4-HNE is a previously unappreciated component of ROS-mediated toxicity encountered by bacteria within eukaryotic hosts.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2050-084X
Relation: https://elifesciences.org/articles/59295; https://doaj.org/toc/2050-084X
DOI: 10.7554/eLife.59295
URL الوصول: https://doaj.org/article/5b6464932a2b4088bf71ee2e3debd3d5
رقم الأكسشن: edsdoj.5b6464932a2b4088bf71ee2e3debd3d5
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2050084X
DOI:10.7554/eLife.59295