Unraveling the dose-response puzzle of L.monocytogenes:A mechanistic approach  

作　　者：S.M.Ashrafur Rahman Daniel Munther Aamir Fazil Ben Smith Jianhong Wu 

机构地区：[1]Laboratory for Industrial and Applied Mathematics,Centre for Disease Modelling,Department of Mathematics and Statistics,York University,Toronto,ON M3J 1P3,Canada [2]Department of Mathematics,Cleveland State University,Cleveland,OH 44115,United States [3]National Microbiology Laboratory,Public Health Agency of Canada,Guelph,ON N1G 5B2,Canada

出　　处：《Infectious Disease Modelling》2016年第1期101-114,共14页传染病建模（英文）

基　　金：Daniel Munther acknowledges support from Cleveland State University startup funding(STARTUP42);Ashrafur Rahman's postdoctoral fellowship is supported by a research contract from the Public Heath Agency of Canada and by the NSERC CREATE project Advanced Disaster,Emergency and Rapid Response Simulations.JianhongWu's research has been funded by the Natural Sciences and Engineering Research Council of Canada and by the Canada Research Chairs program.

摘　　要：Food-borne disease outbreaks caused by Listeria monocytogenes continue to impose heavy burdens on public health in North America and globally.To explore the threat L.monocytogenes presents to the elderly,pregnant woman and immuno-compromised individuals,many studies have focused on in-host infection mechanisms and risk evaluation in terms of dose-response outcomes.However,the connection of these two foci has received little attention,leaving risk prediction with an insufficient mechanistic basis.Consequently,there is a critical need to quantifiably link in-host infection pathways with the doseresponse paradigm.To better understand these relationships,we propose a new mathematical model to describe the gastro-intestinal pathway of L.monocytogenes within the host.The model dynamics are shown to be sensitive to inoculation doses and exhibit bistability phenomena.Applying the model to guinea pigs,we show how it provides useful tools to identify key parameters and to inform critical values of these parameters that are pivotal in risk evaluation.Our preliminary analysis shows that the effect of gastroenvironmental stress,the role of commensal microbiota and immune cells are critical for successful infection of L.monocytogenes and for dictating the shape of the doseresponse curves.

关 键 词：L.monocytogenes DOSE-RESPONSE Mechanistic model Bi-stable Guinea pig 

分 类 号：H31[语言文字—英语]