新東京大学大学院領域創成科学研究科
Why do we die from infection? Evidence for suicidal defense strategy

Abstract.

Why do we sometimes die easily from microbial infection? Ichizo Kobayashi’s group at Department of Medical Genome Science in Graduate School of Frontier Sciences examined the following hypothesis. If a member of a host population dies immediately upon infection aborting pathogen reproduction, this death can protect the host population from secondary infections. The group verified this Suicidal Defense Against Infection hypothesis in large-scale infection experiments linked to computer simulation. These results provide a novel concept for pathogen virulence.

Content.

Why do we sometimes die easily from microbial infection? Expression of virulence and host death will decrease opportunity of pathogen reproduction. Even under such a situation, why do some pathogens show high virulence?

Previously proposed concepts have focused on the pathogen’s strategy such as incomplete adaptation after host jump and within-host competition.

Kobayashi’s group proposed a hypothesis focused on the host strategy (Figure). Usually an infected individual allows multiplication of the pathogen, which infects the other individuals in the population and spread in an epidemic (Figure, left). However, if a member of a host population dies immediately upon infection aborting pathogen reproduction, this death can protect the host population from secondary infections (Figure, right).

The group verified this Suicidal Defense Against Infection hypothesis by developing an experimental infection system involving a large (100,000,000 individuals) population, which was linked to game-theory-based mathematical modeling and a large-scale computer simulation.

In the experiments, E. coli was used as the host and bacteriophage was used as the pathogen. Two lines of the host were prepared: one that allows pathogen multiplication upon infection (S host) (Figure left) and the other that commits suicide immediately upon infection (A host) (Figure right). A host and S host were mixed in a varying ratio and received the pathogen. After incubation for hours, the ratio of the two hosts (A/S) was monitored. 

Two environments were used for the infection. One is well-mixed liquid and corresponds to the absence of spatial structure. Here every participant can interact with another at an equal frequency. The other is within solid agar and corresponds to the presence of spatial structure. Here a participant will preferentially interact with its neighbor. 

In the presence of spatial structure, the host ratio (A/S) increased by two orders of magnitude. This indicates that the Suicidal Defense Against Infection strategy can be successful.

This result was reproduced by a large-scale simulation based on a mathematical model of the evolutionary game theory (non-linear dynamics). In the simulation, infection was reproduced in a double grid with 100000000 squares.

These results lead to a novel concept in microbial virulence, which is of importance in medicine. The analysis system may be useful in analyzing problems in epidemiology of infection.

This work was carried out by the following researchers.
Masaki Fukuyoa,b, Akira Sasakic.d, Ichizo Kobayashia.e.f.

a: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Japan,
b: Research Fellow of the Japan Society for the Promotion of Science (JSPS),
c: Department of Evolutionary Studies of Biosystems (Sokendai-Hayama), The
Graduate University for Advanced Studies (Sokendai), Hayama, Japan,
d: Evolution and Ecology Program,International Institute for Applied Systems Analysis, Laxenburg, Austria,
e: Institute of Medical Science, University of Tokyo, Japan,
f: Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Japan.

Publication:

Scientific Reports (January 30. 2012)
Success of a suicidal defense strategy against infection in a structured habitat.
Masaki Fukuyo, Akira Sasaki, Ichizo Kobayashi.

Inquiry:

Ichizo KOBAYASHI, Ph.D.
Professor, UNIVERSITY OF TOKYO
Department of Medical Genome Sciences,
GRADUATE SCHOOL OF FRONTIER SCIENCE
& INSTITUTE OF MEDICAL SCIENCE
       4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 JAPAN
       PHONE:  Japan (81) 3-5449-5326
       FAX:  Japan (81) 3-5449-5422
       E-mail: ikobaya@ims.u-tokyo.ac.jp
       http://www.ims.u-tokyo.ac.jp/ikobaya

Glossary:

Host: An organism infected with a microorganism.

Attachment

The figure inserted above can be downloaded in the following URL.
http://www.ims.u-tokyo.ac.jp/ikobaya/images/hiEn.png

 

 

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