Network analytics approach towards identifying potential antivirulence drug targets within the Staphylococcus aureus staphyloxanthin biosynthetic network
Network analytics approach towards identifying potential antivirulence drug targets within the Staphylococcus aureus staphyloxanthin biosynthetic network
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DOI：
10.1016/j.abb.2018.03.010
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发表时间：
2018-05-01
影响因子：
3.9
通讯作者：
Imai, Kenichi
中科院分区：
文献类型：
--
作者：
Cueno, Marni E.;Imai, Kenichi
金黄色葡萄球菌与人类中的几种临床显著感染相关，并且与耐药菌株相关的感染频率正在增加。抗病毒策略将药物的目标从细菌生长转移到感染过程，从而导致细菌耐药菌株发展的进化压力较小。葡萄黄质（STX）是由葡萄球菌（S.金黄色葡萄球菌和这种类胡萝卜素作为细菌的重要毒力因子发挥作用。在这项研究中，我们阐明了网络分析是否可以作为一种可行的工具来识别STX生物合成网络中的重要组分，而这些组分反过来又可以作为可能的抗毒力药物靶标。为了确认，我们将我们的结果与能够抑制STX生物合成的已知药物相关联。在整个研究中，我们确定crtN（1）活性和4，4 '-diaponeurosporene量是STX生物合成网络中的重要组成部分，此外，网络分析可以帮助确定STX生物合成网络中的抗病毒药靶点。同样，我们发现网络分析能够同时识别多个潜在目标。因此，我们建议开发一种有效的抗沙门氏菌的药物。金黄色葡萄球菌STX生物合成可能涉及靶向crtN（1）活性、4，4 '-二孢囊孢烯水平或这两种组分。
Staphylococcus aureus is associated with several clinically significant infections among humans and infections associated with antibiotic-resistant strains are growing in frequency. Antivirulence strategies shift the target of drugs from bacterial growth to the infection process resulting to milder evolutionary pressure for the development of bacterial resistant strains. Staphyloxanthin (STX) is a yellowish-orange carotenoid pigment synthesized by S. aureus and this carotenoid functions as an important virulence factor for the bacteria. In this study, we elucidated whether network analytics can be used as a viable tool to identify significant components in the STX biosynthetic network which in-turn could serve as possible antivirulence drug targets. For confirmation, we correlated our results to known drugs that were able to inhibit STX biosynthesis. Throughout this study, we established that crtN(1) activity and 4,4'-diaponeurosporene amounts are significant components in the STX biosynthetic network and, moreover, network analytics can aid in identifying antivirulence drug targets within the STX biosynthetic network. Similarly, we found that network analytics is capable of identifying multiple potential targets simultaneously. Taken together, we propose that an effective antivirulence drug against S. aureus STX biosynthesis would involve targeting crtN(1) activity, 4,4'-diaponeurosporene levels, or both components.