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. © 2012 EMBO and Macmillan Publishers Limited. All rights reserved.
CITATION STYLE
Tan, C., Phillip Smith, R., Srimani, J. K., Riccione, K. A., Prasada, S., Kuehn, M., & You, L. (2012). The inoculum effect and band-pass bacterial response to periodic antibiotic treatment. Molecular Systems Biology, 8. https://doi.org/10.1038/msb.2012.49
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