The new approaches that are needed to deal with this increasing threat will come from the integration of two of the most active areas of biomedical research: the molecular and cellular basis of microbial pathogenesis, and the nature and manipulation of immune defence. In this month's Insight, we examine how bacteria attack and survive in the host, the mechanisms that the host uses to defend itself, and the therapeutic strategies that can be used to buttress these defences. As this is such a large and complex topic, we focus on bacterial disease; important health hazards such as HIV infection and malaria will be addressed in future Insights.
On page 760, Barry Bloom presents an overview of the topic, illustrating the complexity and diversity that arises from the particularity of microbial pathogens. The changing patterns of infectious disease globally and the evolving response strategies are discussed by Mitchell Cohen on page 762. Michael Donnenberg discusses on page 768 the myriad strategies by which enteric pathogens establish infection and survive in the face of an intense onslaught from the host immune response. On page 775, Chris Walsh extends this theme by examining the sophisticated methods that bacteria use to combat antibiotics. Walsh also describes new approaches to the development of novel antibiotics. Several exciting and recent findings have catapulted the innate immune system, which constitutes the first line of defence against infectious disease, from relative obscurity to the forefront of the fight against bacteria. Principal among these findings is the triggering of innate immunity Toll-like receptors on the surface of extracellular bacteria, a subject covered by Alan Aderem and Richard Ulevitch on page 782. Se-Ho Park and Albert Bendelac examine another recent surprise on page 788, namely the ability of mycobacterial lipids to trigger T-cell responses through presentation on non- classical class I molecules. Difficulties in generating vaccines against intracellular pathogens, and strategies to overcome these difficulties are explored on page 793 by Robert Seder and Adrian Hill . Finally, on page 799 Claire Fraser and co-workers update microbial genome sequencing and discuss how our increasing knowledge will provide new approaches to the diagnosis and treatment of infectious disease.
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