Imperial College London
Portrait Picture

Professor Reiko J. Tanaka

Faculty of Engineering, Department of Bioengineering

Professor of Computational Systems Biology & Medicine
 
 
 
//

Contact

 

+44 (0)20 7594 6374r.tanaka Website

 
 
//

Location

 

RSM 3.10Royal School of MinesSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Dominguez-Huettinger:2017:10.3389/fphys.2017.00115,
author = {Dominguez-Huettinger, E and Boon, NJ and Clarke, TB and Tanaka, RJ},
doi = {10.3389/fphys.2017.00115},
journal = {FRONTIERS IN PHYSIOLOGY},
title = {Mathematical Modeling of Streptococcus pneumoniae Colonization, Invasive Infection and Treatment},
url = {http://dx.doi.org/10.3389/fphys.2017.00115},
volume = {8},
year = {2017}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Streptococcus pneumoniae (Sp) is a commensal bacterium that normally resides on the upper airway epithelium without causing infection. However, factors such as co-infection with influenza virus can impair the complex Sp-host interactions and the subsequent development of many life-threatening infectious and inflammatory diseases, including pneumonia, meningitis or even sepsis. With the increased threat of Sp infection due to the emergence of new antibiotic resistant Sp strains, there is an urgent need for better treatment strategies that effectively prevent progression of disease triggered by Sp infection, minimizing the use of antibiotics. The complexity of the host-pathogen interactions has left the full understanding of underlying mechanisms of Sp-triggered pathogenesis as a challenge, despite its critical importance in the identification of effective treatments. To achieve a systems-level and quantitative understanding of the complex and dynamically-changing host-Sp interactions, here we developed a mechanistic mathematical model describing dynamic interplays between Sp, immune cells, and epithelial tissues, where the host-pathogen interactions initiate. The model serves as a mathematical framework that coherently explains various in vitro and in vitro studies, to which the model parameters were fitted. Our model simulations reproduced the robust homeostatic Sp-host interaction, as well as three qualitatively different pathogenic behaviors: immunological scarring, invasive infection and their combination. Parameter sensitivity and bifurcation analyses of the model identified the processes that are responsible for qualitative transitions from healthy to such pathological behaviors. Our model also predicted that the onset of invasive infection occurs within less than 2 days from transient Sp challenges. This prediction provides arguments in favor of the use of vaccinations, since adaptive immune responses cannot be developed de novo in such a short time. We furthe
AU  - Dominguez-Huettinger,E
AU  - Boon,NJ
AU  - Clarke,TB
AU  - Tanaka,RJ
DO  - 10.3389/fphys.2017.00115
PY  - 2017///
SN  - 1664-042X
TI  - Mathematical Modeling of Streptococcus pneumoniae Colonization, Invasive Infection and Treatment
T2  - FRONTIERS IN PHYSIOLOGY
UR  - http://dx.doi.org/10.3389/fphys.2017.00115
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000395104400001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/45885
VL  - 8
ER  -
Download