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Beyond the spore, the exosporium sugar anthrose impacts vegetative Bacillus anthracis gene regulation in cis and trans

Two diagrams are shown to detail the differences in subcutaneous anthrax infection. The left panel demonstrates anthrose positive spores of anthrax. The right demonstrates anthrose negative spores of anthrax.
Figure 9: Shows how, in the course of subcutaneous infection, anthrose positive anthrax spores germinate and secrete toxin to enable local infections to spread systemically according to the jail-break hypothesis of dissemination (Fig. 9A). In contrast, anthrose negative spores do not germinate as fast and interact more efficiently with professional phagocytes at the site of inoculation, permitting phagocyte-assisted dissemination to secondary tissues as outlined in the trojan horse model of anthrax dissemination.

NORRIS, METRAILER, JIRANANTASAK, BLACKBURN – Beyond the spore, the exosporium sugar anthrose impacts vegetative Bacillus anthracis gene regulation in cis and trans

Michael Norris, Andrew Bluhm, Morgan Metrailer, Treenate Jiranantasak, Alexander Kirpich, Ted Hadfield, Jose Miguel Ponciano, Jason Blackburn

Article first published online: 28 March 2023

DOI: https://doi.org/10.1038/s41598-023-32162-x

ABSTRACT: The Bacillus anthracis exosporium nap is the outermost portion of spore that interacts with the environment and host systems. Changes to this layer have the potential to impact wide-ranging physiological and immunological processes. The unique sugar, anthrose, normally coats the exosporium nap at its most distal points. We previously identified additional mechanisms rendering B. anthracis anthrose negative. In this work, several new ant − B. anthracis strains are identified and the impact of anthrose negativity on spore physiology is investigated. We demonstrate that live-attenuated Sterne vaccines as well as culture filtrate anthrax vaccines generate antibodies targeting non-protein components of the spore. The role of anthrose as a vegetative B. anthracis Sterne signaling molecule is implicated by luminescent expression strain assays, RNA-seq experiments, and toxin secretion analysis by western blot. Pure anthrose and the sporulation-inducing nucleoside analogue decoyinine had similar effects on toxin expression. Co-culture experiments demonstrated gene expression changes in B. anthracis depend on intracellular anthrose status (cis) in addition to anthrose status of extracellular interactions (trans). These findings provide a mechanism for how a unique spore-specific sugar residue affects physiology, expression and genetics of vegetative B. anthracis with impacts on the ecology, pathogenesis, and vaccinology of anthrax.

Read the full publication in Scientific Reports.