The exosporium is not unique to Bacillus anthracis and is present in all members of the B.cereus group and some clostridia. The function this complex structure plays in the survival of these spores is as yet unknown. One possibility is that it acts as a physical barrier passively reacting with biocides before they have the chance to reach essential molecules located within the spore core. We propose to determine the contribution the exosporium makes to environmental survival and biocide resistance. In addition the exosporium contributes to intracellular survival by masking inflammatory signals located in the spore coat thus preventing the infected macrophage from mounting a pro-inflammatory immune response. In addition to playing a passive role in survival we recently reported the presence of biologically active enzymes such as alanine racemase within the exosporium which prevent germination under sub-optimal conditions encountered in soil and infection. This is an extremely novel concept as the spore has long been thought of as an inert particle who’s intrinsic resistance to environmental insult enables it to lie dormant until conditions are conducive to growth. In addition to regulating germination the exosporium contains enzymes such as superoxide dismutase and an arginase which contribute to the intracellular survival of the organism by inhibiting the activity of antibacterial radicals. By understanding the contribution the exosporium makes to intracellular survival we will be able to design therapeutics which enhance the ability of the macrophage to kill the organism. This proposal represents the continuation of a program of research initiated by the applicant while working in the U.S. Its funding will enable the researcher to establish his own research effort in the UK by building on the earlier data and will continue the links forged with US colleagues which to date has yielded five publications.