Global efforts are being made to achieve the clinical implementation of pre-emptive medicine for Staphylococcus aureus (S. aureus) infectious disease, which will realize both early detection at the pre-symptom stage and bacteriostatic therapy by antibiotic-free medicine in a future. Several research groups proposed the intercellular signal transduction factor (auto-inducing peptide: AIP) antibody, the synthesised AIP analogues and a cyclic depsipeptide with high constitutional similarity to AIP as a candidate of the pre-emptive medicine for S. aureus infectious disease. In this paper, to evaluate a validity of them, we mathematically explored both a pre-symptom associated with the pathogenic expression process of S. aureus and several therapeutic targets that delay or suppress the appearance of the pre-symptom. The stochastic mathematical analysis identified a peak of fluctuation in intracellular AgrD concentration as the pre-symptom. Moreover, employing parameter sensitivity analysis, the enhancement of binding inhibition between AgrC receptor and AIP was identified as effective therapeutic target. Based on these findings, we evaluated a feasibility of above-mentioned candidates, and concluded that the continuous application of AgrC receptor antagonists, such as the synthesised AIP analogues and a cyclic depsipeptide with high constitutional similarity to AIP, is useful as pre-emptive medicine for S. aureus infectious disease.

全球正在努力实现金黄色葡萄球菌（S. aureus）传染病抢先药物的临床应用，未来将实现症状前早期发现和无抗生素药物抑菌治疗。多个研究小组提出细胞间信号转导因子（自动诱导肽：AIP）抗体、合成的AIP类似物和与AIP具有高度相似性的环状缩酚肽作为金黄色葡萄球菌感染性疾病的先发制人候选药物。在本文中，为了评估它们的有效性，我们从数学上探讨了与金黄色葡萄球菌致病性表达过程相关的前症状以及一些延迟或抑制症状前出现的治疗靶点。随机数学分析将细胞内 AgrD 浓度波动的峰值确定为前症状。此外，采用参数敏感性分析，AgrC 受体与 AIP 之间结合抑制的增​​强被确定为有效的治疗靶点。基于这些发现，我们评估了上述候选药物的可行性，并得出结论，持续应用 AgrC 受体拮抗剂，例如合成的 AIP 类似物和与 AIP 具有高度相似性的环状缩酚肽，可用作抢先药物用于金黄色葡萄球菌传染病。