ROLEEXOSPORIUM

The contribution of the exosporium of Bacillus anthracis to survival

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 Obiettivo del progetto (Objective)

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.

Introduzione (Teaser)

An exosporium is a thin covering lying over a spore coat. It acts like a filter and helps mount resistance to many toxic molecules.

Descrizione progetto (Article)

The existence of the exosporium alone protects inner cell structures by masking inflammatory signals in the spore coat, and further contributes to intracellular survival by inhibiting the activity of antibacterial radicals.

The exosporium is present in Bacillus anthracis, a spore-forming bacterium, all members of the Bacillus cereus group and some clostridia, such as Clostridium difficile. The latter forms a spore similar in structure to that of the complex B. anthracis. Researchers are working to discover the function of the coat lining structure in the survival of these spores.

'The contribution of the exosporium of Bacillus anthracis to survival' (Roleexosporium) is a project aiming to determine how the exosporium facilitates survival of B. anthracis, contributes to biocide resistance, and also to virulence and in vivo germination. Work on the third objective was undertaken together with colleagues in the US. To date, a fully functional research laboratory for these studies has been established at the UK's Cardiff University.

Preliminary studies have successfully characterised the properties of wild-type spores and determined their ability to germinate in response to various triggers. Researchers will compare these results with those obtained in studies of exosporium-deficient spores. Notably, within the first 18 months of the project, Roleexosporium researchers developed a fully defined minimal medium capable of supporting the growth of B. anthracis.

In investigating how exosporium contributes to biocide resistance, preliminary studies found that sonicated (physically altered) spores were far more sensitive to the chlorine-releasing biocide Chlorox than their wild-type counterparts. This suggests that the exosporium acts as a physical barrier and reacts with the biocide before it can invade molecules in the spore's core.

Other studies have been undertaken to characterise the intracellular survival of B. anthracis spores after uptake by macrophages, white blood cells that work to eradicate pathogens. Performed in collaboration with US colleagues, this work highlights the important role that bacterial arginase has in directing the immune response of infected cells. The study is described in a manuscript that has been accepted for publication by the Current Microbiology journal.