The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.
The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.
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DOI：
10.1038/msb.2012.49
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发表时间：
2012
影响因子：
9.9
通讯作者：
中科院分区：
文献类型：
--
作者：
接种物效应（IE）是指随着细菌密度的增加，抗生素的效力降低。它代表了抗生素耐受性的独特策略，并且它可以使细菌感染的有效抗生素治疗的设计复杂化。为了深入了解这一现象，我们分析了实验室大肠杆菌菌株对靶向核糖体的抗生素的反应。我们表明，IE可以解释为细菌生长的抑制。这种双稳定性的一个关键要求是核糖体的降解足够快，这可能是由维生素诱导的热休克反应引起的。此外，引发IE的抗生素可导致细菌生长对周期性抗生素治疗的“带通”反应：治疗功效在治疗的中间频率下急剧降低。我们提出的IE机制可能普遍适用于用靶向核糖体的抗生素治疗的其他细菌物种。
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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影响因子：
64.5
作者：
Kohanski, Michael A.;Dwyer, Daniel J.;Collins, James J.
通讯作者：
Collins, James J.
影响因子：
4.9
作者：
Chin, Judy N.;Rybak, Michael J.;Savage, Paul B.
通讯作者：
Savage, Paul B.
影响因子：
64.5
作者：
Bollenbach T;Quan S;Chait R;Kishony R
通讯作者：
Kishony R
DOI：
10.1073/pnas.81.21.6647
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
GOFF, SA;CASSON, LP;GOLDBERG, AL
通讯作者：
GOLDBERG, AL
影响因子：
2.4
作者：
Duraisingh, MT;Jones, P;Warhurst, DC
通讯作者：
Warhurst, DC