The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.
Journal Article (Journal Article)
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.
- Published version (via Digital Object Identifier)
- Pubmed Central version
- Open Access Copy from Duke
- Link to Item
- Tan, C; Smith, RP; Srimani, JK; Riccione, KA; Prasada, S; Kuehn, M; You, L
Volume / Issue
- 8 /
Start / End Page
- 617 -
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)