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

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.

SUBMITTER: Tan C

PROVIDER: S-EPMC3472685 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Tan Cheemeng C Smith Robert Phillip RP Srimani Jaydeep K JK Riccione Katherine A KA Prasada Sameer S Kuehn Meta M You Lingchong L

Molecular systems biology 20120101

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 ...[more]

PMID: 23047527

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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. This model is hosted on BioModels Database and identified by: MODEL1208300000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Background First-pass reperfusion (FPR) is associated with favorable outcome after endovascular treatment. It is unknown whether this effect is independent of patient characteristics and whether FPR has better outcomes compared with excellent reperfusion (Expanded Thrombolysis in Cerebral Infarction [eTICI] 2C-3) after multiple-passes reperfusion. We aimed to evaluate the association between FPR and outcome with adjustment for patient, imaging, and treatment characteristics to single out the contribution of FPR. Methods and Results FPR was defined as eTICI 2C-3 after 1 pass. Multivariable regression models were used to investigate characteristics associated with FPR and to investigate the effect of FPR on outcomes. We included 2686 patients of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry. Factors associated with FPR were as follows: history of hyperlipidemia (adjusted odds ratio [OR], 1.05; 95% CI, 1.01-1.10), middle cerebral artery versus intracranial carotid artery occlusion (adjusted OR, 1.11; 95% CI, 1.06-1.16), and aspiration versus stent thrombectomy (adjusted OR, 1.07; 95% CI, 1.03-1.11). Interventionist experience increased the likelihood of FPR (adjusted OR, 1.03 per 50 patients previously treated; 95% CI, 1.01-1.06). Adjusted for patient, imaging, and treatment characteristics, FPR remained associated with a better 24-hour National Institutes of Health Stroke Scale (NIHSS) score (-37%; 95% CI, -43% to -31%) and a better modified Rankin Scale (mRS) score at 3 months (adjusted common OR, 2.16; 95% CI, 1.83-2.54) compared with no FPR (multiple-passes reperfusion+no excellent reperfusion), and compared with multiple-passes reperfusion alone (24-hour NIHSS score, (-23%; 95% CI, -31% to -14%), and mRS score (adjusted common OR, 1.45; 95% CI, 1.19-1.78)). Conclusions FPR compared with multiple-passes reperfusion is associated with favorable outcome, independently of patient, imaging, and treatment characteristics. Factors associated with FPR were the experience of the interventionist, history of hyperlipidemia, location of occluded artery, and use of an aspiration device compared with stent thrombectomy.

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

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

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