Growth productivity as a determinant of the inoculum effect for bactericidal antibiotics.
Growth productivity as a determinant of the inoculum effect for bactericidal antibiotics.
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DOI：
10.1126/sciadv.add0924
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发表时间：
2022-12-14
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
了解细菌群体抵抗抗生素的机制对进化、微生物生态学和公共卫生都有意义。接种物效应（IE），其中抗生素效力随着细菌种群密度的增加而下降，已观察到多种细菌物种和抗生素。已经提出了几种解释IE的机制，但大多数缺乏实验证据或无法解释多种抗生素的IE。我们发现，生长生产力，生长和代谢的综合作用，可以解释IE多种杀菌抗生素和细菌物种。通量平衡分析和全基因组建模的指导下，我们表明，在生长培养基中提供的碳源决定生长生产力。如果增长生产率足够高，IE就会被淘汰。我们的研究结果可能会导致在临床上减少IE的方法，有助于标准化抗生素的分析，并进一步了解细菌如何进化耐药性。生长速率和代谢之间的相互作用可以解释多种杀菌抗生素的接种效果。
Understanding the mechanisms by which populations of bacteria resist antibiotics has implications in evolution, microbial ecology, and public health. The inoculum effect (IE), where antibiotic efficacy declines as the density of a bacterial population increases, has been observed for multiple bacterial species and antibiotics. Several mechanisms to account for IE have been proposed, but most lack experimental evidence or cannot explain IE for multiple antibiotics. We show that growth productivity, the combined effect of growth and metabolism, can account for IE for multiple bactericidal antibiotics and bacterial species. Guided by flux balance analysis and whole-genome modeling, we show that the carbon source supplied in the growth medium determines growth productivity. If growth productivity is sufficiently high, IE is eliminated. Our results may lead to approaches to reduce IE in the clinic, help standardize the analysis of antibiotics, and further our understanding of how bacteria evolve resistance. Interactions between growth rate and metabolism can explain inoculum effect for multiple bactericidal antibiotics.
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细菌群落抗菌素耐药性的生态学和进化。
DOI：
10.1038/s41396-020-00832-7
发表时间：
2021-04
期刊：
The ISME journal
影响因子：
--
作者：
Bottery MJ;Pitchford JW;Friman VP
通讯作者：
Friman VP
影响因子：
6.4
作者：
Glazyrina J;Materne EM;Dreher T;Storm D;Junne S;Adams T;Greller G;Neubauer P
通讯作者：
Neubauer P
影响因子：
4.6
作者：
Bren A;Park JO;Towbin BD;Dekel E;Rabinowitz JD;Alon U
通讯作者：
Alon U
影响因子：
3.2
作者：
ANDERSEN, PS;FREES, D;MYGIND, B
通讯作者：
MYGIND, B
影响因子：
4.4
作者：
Augustin, JC;Brouillaud-Delattre, A;Carlier, V
通讯作者：
Carlier, V