The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.

Published

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.

Full Text

Duke Authors

Cited Authors

  • Tan, C; Smith, RP; Srimani, JK; Riccione, KA; Prasada, S; Kuehn, M; You, L

Published Date

  • 2012

Published In

Volume / Issue

  • 8 /

Start / End Page

  • 617 -

PubMed ID

  • 23047527

Pubmed Central ID

  • 23047527

Electronic International Standard Serial Number (EISSN)

  • 1744-4292

Digital Object Identifier (DOI)

  • 10.1038/msb.2012.49

Language

  • eng

Conference Location

  • England