Publication Date:
2013-11-30
Description:
To predict the emergence of antibiotic resistance, quantitative relations must be established between the fitness of drug-resistant organisms and the molecular mechanisms conferring resistance. These relations are often unknown and may depend on the state of bacterial growth. To bridge this gap, we have investigated Escherichia coli strains expressing resistance to translation-inhibiting antibiotics. We show that resistance expression and drug inhibition are linked in a positive feedback loop arising from an innate, global effect of drug-inhibited growth on gene expression. A quantitative model of bacterial growth based on this innate feedback accurately predicts the rich phenomena observed: a plateau-shaped fitness landscape, with an abrupt drop in the growth rates of cultures at a threshold drug concentration, and the coexistence of growing and nongrowing populations, that is, growth bistability, below the threshold.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059556/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059556/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deris, J Barrett -- Kim, Minsu -- Zhang, Zhongge -- Okano, Hiroyuki -- Hermsen, Rutger -- Groisman, Alexander -- Hwa, Terence -- 1 U54 CA143803/CA/NCI NIH HHS/ -- R01 GM095903/GM/NIGMS NIH HHS/ -- R01-GM095903/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 29;342(6162):1237435. doi: 10.1126/science.1237435.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of California at San Diego, La Jolla, CA 92093-0374, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24288338" target="_blank"〉PubMed〈/a〉
Keywords:
*Adaptation, Physiological
;
Chloramphenicol/metabolism/pharmacology
;
Chloramphenicol O-Acetyltransferase/biosynthesis
;
*Drug Resistance, Bacterial
;
Escherichia coli/*drug effects/genetics/*growth & development
;
Gene Expression Regulation, Bacterial/drug effects
;
*Genetic Fitness
;
Models, Biological
;
Protein Biosynthesis/drug effects
;
Protein Synthesis Inhibitors/metabolism/*pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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