TY - JOUR
T1 - Mathematical analysis-based feasibility study of pre-emptive medicine for Staphylococcus aureus infectious disease
T2 - Early detection and antibiotic-free maintenance therapy
AU - Hamada, Hiroyuki
AU - Kurinomaru, Satoshi
AU - Ohitokata, Shogo
AU - Yang, Yakun
AU - Asamura, Kenta
AU - Deguchi, Mari
AU - Motomura, Yohei
AU - Iwasaki, Akiyuki
AU - Sekiguchi, Tatsuya
AU - Hanai, Taizo
AU - Okamoto, Masahiro
N1 - Funding Information:
This work was supported by JSPS KAKENHI Grant Number JP16K12912 . We thank members from the committee for application of new technologies to blood purification therapy in Japanese Society of Dialysis Therapy who provided insight and expertise that greatly assisted the research.
Publisher Copyright:
© 2020
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.biosystems.2020.104238
DO - 10.1016/j.biosystems.2020.104238
M3 - Article
C2 - 32861801
AN - SCOPUS:85090989244
VL - 198
JO - Currents in modern biology
JF - Currents in modern biology
SN - 0303-2647
M1 - 104238
ER -