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Prog Drug Res. 2007;64:239, 241-63.

Biological robustness in complex host-pathogen systems.

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The Systems Biology Institute, Suite 6A, M31 6-31-15 Jingumae, Shibuya, Tokyo 150-0001, Japan.


Infectious diseases are still the number one killer of human beings. Even in developed countries, infectious diseases continue to be a major health threat. This article explores a conceptual framework for understanding infectious diseases in the context of the complex dynamics between microbe and host, and explores theoretical strategies for anti-infectives. The central pillar of this conceptual framework is that biological robustness is a fundamental property of systems that is closely interlinked with the evolution of symbiotic host-pathogen systems. There are specific architectural features of such robust yet evolvable systems and interpretable trade-offs between robustness, fragility, resource demands, and performance. This concept applies equally to both microbes and host. Pathogens have evolved to exploit the host using various strategies as well as effective escape mechanisms. Modular pathogenicity islands (PAI) derived from horizontal gene transfer, highly variable surface molecules, and a range of other countermeasures enhance the robustness of a pathogen against attacks from the host immune system. The host has likewise evolved complex defensive mechanisms to protect itself against pathogenic threats, but the host immune system includes several trade-offs that can be exploited by pathogens and induces undesirable inflammatory reactions. Due to the complexity of the dynamics emerging from the interactions of multiple microbes and a host, effective counter-measures require an in-depth understanding of system dynamics as well as detailed molecular mechanisms of the processes that are involved.

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