隐藏的抑制性相互作用在高阶药物组合中很常见。
Hidden suppressive interactions are common in higher-order drug combinations.
作者信息
Lozano-Huntelman Natalie Ann, Zhou April, Tekin Elif, Cruz-Loya Mauricio, Østman Bjørn, Boyd Sada, Savage Van M, Yeh Pamela
机构信息
Ecology and Evolutionary Biology, University of California, Los Angeles, 90095, USA.
Computational and Systems Biology, University of California, Los Angeles, 90095, USA.
出版信息
iScience. 2021 Mar 26;24(4):102355. doi: 10.1016/j.isci.2021.102355. eCollection 2021 Apr 23.
The rapid increase of multi-drug resistant bacteria has led to a greater emphasis on multi-drug combination treatments. However, some combinations can be suppressive-that is, bacteria grow faster in some drug combinations than when treated with a single drug. Typically, when studying interactions, the overall effect of the combination is only compared with the single-drug effects. However, doing so could miss "hidden" cases of suppression, which occur when the highest order is suppressive compared with a lower-order combination but not to a single drug. We examined an extensive dataset of 5-drug combinations and all lower-order-single, 2-, 3-, and 4-drug-combinations. We found that a majority of all combinations-54%-contain hidden suppression. Examining hidden interactions is critical to understanding the architecture of higher-order interactions and can substantially affect our understanding and predictions of the evolution of antibiotic resistance under multi-drug treatments.
多重耐药菌的迅速增加使得人们更加重视联合使用多种药物进行治疗。然而，有些药物组合可能具有抑制作用——也就是说，细菌在某些药物组合中的生长速度比使用单一药物时更快。通常，在研究相互作用时，仅将药物组合的总体效果与单一药物的效果进行比较。然而，这样做可能会忽略“隐藏”的抑制情况，即当高阶组合与低阶组合相比具有抑制作用，但与单一药物相比则不然时，就会出现这种情况。我们研究了一个包含5种药物组合以及所有低阶单一药物、2种、3种和4种药物组合的广泛数据集。我们发现，所有组合中有54%包含隐藏抑制作用。研究隐藏的相互作用对于理解高阶相互作用的结构至关重要，并且会极大地影响我们对多重药物治疗下抗生素耐药性演变的理解和预测。
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