Chemical proteomics reveals mechanisms of bacterial response to ROS mediated by antibiotics
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ABSTRACT:
ORGANISM(S): Escherichia Coli
SUBMITTER: 
Jing Yang
PROVIDER: PXD046916 | iProX | Tue Nov 14 00:00:00 GMT 2023
REPOSITORIES: iProX
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Project description:Tan2012 - Antibiotic Treatment, Inoculum Effect
The efficacy of many antibiotics decreases with increasing bacterial density, a phenomenon called the ‘inoculum effect’ (IE). This study reveals that, for ribosome-targeting antibiotics, IE is due to bistable inhibition of bacterial growth, which reduces the efficacy of certain treatment frequencies.
This model is described in the article:
The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.
Tan C, Phillip Smith R, Srimani JK, Riccione KA, Prasada S, Kuehn M, You L.
Mol Syst Biol. 2012 Oct 9; 8:617
Abstract:
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.
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