Complex and unexpected outcomes of antibiotic therapy against a polymicrobial infection.
Complex and unexpected outcomes of antibiotic therapy against a polymicrobial infection.
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DOI：
10.1038/s41396-022-01252-5
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发表时间：
2022-09
期刊：
影响因子：
11
通讯作者：
Quinn, Robert A.
中科院分区：
文献类型：
--
作者：
Ghuneim, Lydia-Ann J.;Raghuvanshi, Ruma;Neugebauer, Kerri A.;Guzior, Douglas V.;Christian, Martin H.;Schena, Bella;Feiner, Jeremiah M.;Castillo-Bahena, Alicia;Mielke, Jenna;McClelland, Marc;Conrad, Douglas;Klapper, Isaac;Zhang, Tianyu;Quinn, Robert A.
抗生素是我们治疗复杂感染的主要方法，但我们对这些药物如何影响微生物群落的了解很少。为了更好地了解抗微生物对宿主相关微生物群落的影响，我们用11种不同的抗生素处理了囊性纤维化患者（CACF，n = 24）的培养痰微生物组，并在粘液堵塞的细支气管微观世界中进行了基于理论和数学建模的预测。我们在体外确定的经计算机模拟预测的治疗结局为：1）群落死亡，2）群落耐药性，3）病原体杀灭和4）发酵罐杀灭。然而，当应用抗生素时，未预测到的两个结果是5）总细菌负荷（TBL）变化很小的群落概况变化，和6）TBL增加。在17.8%的样本中观察到后一种结果，TBL增加大于20%，6.8%的样本增加大于40%，表明在抗生素存在下社区承载能力显著增加。迭代的数学模型表明，TBL的增加是由于厌氧发酵的pH依赖性抑制病原体的厌氧介导的释放。这些动力学在体外验证时，杀死发酵导致更高的社区承载能力相比，没有抗生素的控制。抗生素治疗期间痰液样本的宏基因组测序显示临床样本中存在类似的动力学。这项研究表明，复杂的微生物生态决定了抗生素治疗对多微生物感染的结果。
Antibiotics are our primary approach to treating complex infections, yet we have a poor understanding of how these drugs affect microbial communities. To better understand antimicrobial effects on host-associated microbial communities we treated cultured sputum microbiomes from people with cystic fibrosis (pwCF, n = 24) with 11 different antibiotics, supported by theoretical and mathematical modeling-based predictions in a mucus-plugged bronchiole microcosm. Treatment outcomes we identified in vitro that were predicted in silico were: 1) community death, 2) community resistance, 3) pathogen killing, and 4) fermenter killing. However, two outcomes that were not predicted when antibiotics were applied were 5) community profile shifts with little change in total bacterial load (TBL), and 6) increases in TBL. The latter outcome was observed in 17.8% of samples with a TBL increase of greater than 20% and 6.8% of samples with an increase greater than 40%, demonstrating significant increases in community carrying capacity in the presence of an antibiotic. An iteration of the mathematical model showed that TBL increase was due to antibiotic-mediated release of pH-dependent inhibition of pathogens by anaerobe fermentation. These dynamics were verified in vitro when killing of fermenters resulted in a higher community carrying capacity compared to a no antibiotic control. Metagenomic sequencing of sputum samples during antibiotic therapy revealed similar dynamics in clinical samples. This study shows that the complex microbial ecology dictates the outcomes of antibiotic therapy against a polymicrobial infection.
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影响因子：
4.6
作者：
Lamoureux C;Guilloux CA;Beauruelle C;Gouriou S;Ramel S;Dirou A;Le Bihan J;Revert K;Ropars T;Lagrafeuille R;Vallet S;Le Berre R;Nowak E;Héry-Arnaud G
通讯作者：
Héry-Arnaud G
影响因子：
9.2
作者：
Almeida A;Mitchell AL;Tarkowska A;Finn RD
通讯作者：
Finn RD
影响因子：
3.7
作者：
Bacci, Giovanni;Paganin, Patrizia;Mengoni, Alessio
通讯作者：
Mengoni, Alessio
影响因子：
3.1
作者：
DEANGELIS, DL;WATERHOUSE, JC;ONEILL, RV
通讯作者：
ONEILL, RV
影响因子：
6.4
作者：
Jean-Pierre F;Vyas A;Hampton TH;Henson MA;O'Toole GA
通讯作者：
O'Toole GA