Abstract
Bacteria that grow extracellularly within deep tissue sites often establish microcolonies that resist attack by host innate immune mechanisms. Using Yersinia pseudotuberculosis disease in the mouse as a model infection system, we show that individual microcolonies are separated into three subpopulations, with two groups directed toward protecting the microcolony from either cellular or humoral innate immune functions respectively. The third population profits from the activities of the first two groups, and appears to replicate in an environment largely protected from host attack. Mutations that cause dysfunctional interactions with humoral innate immune function result in destruction of the microcolony, demonstrating that the failure of one subpopulation to respond to the host has disastrous consequences for the population as a whole.