Early Circulating Edema Factor in Inhalational Anthrax Infection: Does It Matter?

Anthrax toxins are critical virulence factors of Bacillus anthracis and Bacillus cereus strains that cause anthrax-like disease, composed of a common binding factor, the protective antigen (PA), and two enzymatic proteins, lethal factor (LF) and edema factor (EF). While PA is required for endocytosis and activity of EF and LF, several studies showed that these enzymatic factors disseminate within the body in the absence of PA after intranasal infection. In an effort to understand the impact of EF in the absence of PA, we used a fluorescent EF chimera to facilitate the study of endocytosis in different cell lines. Unexpectedly, EF was found inside cells in the absence of PA and showed a pole-dependent endocytosis. However, looking at enzymatic activity, PA was still required for EF to induce an increase in intracellular cAMP levels. Interestingly, the sequential delivery of EF and then PA rescued the rise in cAMP levels, indicating that PA and EF may functionally associate during intracellular trafficking, as well as it did at the cell surface. Our data shed new light on EF trafficking and the potential location of PA and EF association for optimal cytosolic delivery.

Pathogenic Bacilli as an Emerging Biothreat?

Bacillus anthracis, present as a very durable endospore in soil, causes zoonotic illness which is mainly associated with herbivores and domestic animals. Human cases are scarce and often involve populations close to infected livestock. If anthrax is no longer of public health concern in developed countries, B. anthracis is one of the top-tier biological weapon agents. It is classified by the CDC as a category A agent. Since 1994, emerging strains of Bacillus cereus have been associated with anthrax-like disease in mammals. Some clinical strains of B. cereus harbor anthrax-like plasmid genes (pXO1 and pXO2) associated with non-human primate and human infections, with the same clinical presentation of inhalation anthrax and mortality rates. Although currently restricted to certain limited areas of circulation, the emergence of these new strains of B. cereus extends the list of potential agents possibly usable for bioterrorism or as a biological weapon. It is therefore important to improve our knowledge of the phylogeny within the B. cereus sensu lato group to better understand the origin of these strains. We can then more efficiently monitor the emergence of new strains to better control the risk of infection and limit potentially malicious uses.

Differential serological and neutralizing antibody dynamics after an infection by a single SARS-CoV-2 strain.

BACKGROUND: We report here the case of two coworkers infected by the same SARS-CoV-2 strain, presenting two different immunological outcomes. CASE: One patient presented a strong IgG anti-receptor-binding domain immune response correlated with a low and rapidly decreasing titer of neutralizing antibodies. The other patient had a similar strong IgG anti-receptor-binding domain immune response but high neutralizing antibody titers. DISCUSSION AND CONCLUSION: Thus, host individual factors may be the main drivers of the immune response varying with age and clinical severity.

Micropatterned macrophage analysis reveals global cytoskeleton constraints induced by Bacillus anthracis edema toxin.

Bacillus anthracis secretes the edema toxin (ET) that disrupts the cellular physiology of endothelial and immune cells, ultimately affecting the adherens junction integrity of blood vessels that in turn leads to edema. The effects of ET on the cytoskeleton, which is critical in cell physiology, have not been described thus far on macrophages. In this study, we have developed different adhesive micropatterned surfaces (L and crossbow) to control the shape of bone marrow-derived macrophages (BMDMs) and primary peritoneal macrophages. We found that macrophage F-actin cytoskeleton adopts a specific polar organization slightly different from classical human HeLa cells on the micropatterns. Moreover, ET induced a major quantitative reorganization of F-actin within 16 h with a collapse at the nonadhesive side of BMDMs along the nucleus. There was an increase in size and deformation into a kidney-like shape, followed by a decrease in size that correlates with a global cellular collapse. The collapse of F-actin was correlated with a release of focal adhesion on the patterns and decreased cell size. Finally, the cell nucleus was affected by actin reorganization. By using this technology, we could describe many previously unknown macrophage cellular dysfunctions induced by ET. This novel tool could be used to analyze more broadly the effects of toxins and other virulence factors that target the cytoskeleton.