Journal
MOLECULAR SYSTEMS BIOLOGY
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/msb.2012.49
Keywords
antibiotic; bacteria; bistability; inoculum effect
Categories
Funding
- National Science Foundation [BES-0625213]
- National Science Foundation Career Award [CBET-0953202]
- National Institutes of Health [1P50GM081883, 1R01GM098642]
- DuPont Young Professorship
- David and Lucile Packard Fellowship
- Medtronic Fellowship
- Lane Postdoctoral Fellowship
- Pratt Fellowship
- National Science Foundation Graduate Fellowship
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [0953202] Funding Source: National Science Foundation
Ask authors/readers for more resources
The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. To gain insight into this phenomenon, we have analyzed responses of a lab strain of Escherichia coli to antibiotics that target the ribosome. We show that the IE can be explained by bistable inhibition of bacterial growth. A critical requirement for this bistability is sufficiently fast degradation of ribosomes, which can result from antibiotic-induced heat-shock response. Furthermore, antibiotics that elicit the IE can lead to 'band-pass' response of bacterial growth to periodic antibiotic treatment: the treatment efficacy drastically diminishes at intermediate frequencies of treatment. Our proposed mechanism for the IE may be generally applicable to other bacterial species treated with antibiotics targeting the ribosomes. Molecular Systems Biology 8: 617; published online 9 October 2012; doi:10.1038/msb.2012.49 Subject Categories: simulation and data analysis; microbiology & pathogens
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available