کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2037400 1072316 2009 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Nonoptimal Microbial Response to Antibiotics Underlies Suppressive Drug Interactions
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی، ژنتیک و زیست شناسی مولکولی (عمومی)
پیش نمایش صفحه اول مقاله
Nonoptimal Microbial Response to Antibiotics Underlies Suppressive Drug Interactions
چکیده انگلیسی

SummarySuppressive drug interactions, in which one antibiotic can actually help bacterial cells to grow faster in the presence of another, occur between protein and DNA synthesis inhibitors. Here, we show that this suppression results from nonoptimal regulation of ribosomal genes in the presence of DNA stress. Using GFP-tagged transcription reporters in Escherichia coli, we find that ribosomal genes are not directly regulated by DNA stress, leading to an imbalance between cellular DNA and protein content. To test whether ribosomal gene expression under DNA stress is nonoptimal for growth rate, we sequentially deleted up to six of the seven ribosomal RNA operons. These synthetic manipulations of ribosomal gene expression correct the protein-DNA imbalance, lead to improved survival and growth, and completely remove the suppressive drug interaction. A simple mathematical model explains the nonoptimal regulation of ribosomal genes under DNA stress as a side effect of their optimal regulation in different nutrient environments. These results reveal the genetic mechanism underlying an important class of suppressive drug interactions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 139, Issue 4, 13 November 2009, Pages 707–718
نویسندگان
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