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Very early blood diffusion of the active lethal and edema factors of Bacillus anthracis after intranasal infection

Rougeaux, C;Becher, F;Goossens, PL;Tournier, JN;

Lethal and edema toxins are critical virulence factors of Bacillus anthracis. Few data are available on their presence in the early stage of intranasal infection. To investigate the diffusion of edema and lethal factors (EF and LF respectively), we use sensitive quantitative methods to measure their enzymatic activities in mice intranasally challenged with a wild type B. anthracis strain or with an isogenic mutant deficient for the protective antigen (PA). 1 hour after mouse challenge, while only 7% of mice presented bacteremia, LF and EF were detected in the blood of 100% and 42% of mice respectively. PA facilitated the diffusion of LF and EF into the blood compartment. Toxins played a significant role in the systemic dissemination of B. anthracis in the blood, spleen and liver. A mouse model of intoxination further confirmed that LT and ET could diffuse rapidly in the circulation, independently of bacteria. In this inhalational model, toxins have disseminated rapidly in the blood, playing a significant and novel role in the early systemic diffusion of bacteria, demonstrating that they may represent a very early target for the diagnosis and the treatment of anthrax. The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.