, "la maladie du charbon", Toxins, and Institut Pasteur.

Institut Pasteur and have enjoyed a relationship lasting almost 120 years, starting from its foundation and the pioneering work of Louis Pasteur in the nascent fields of microbiology and vaccination, and blooming after 1986 following the molecular biology/genetic revolution. This contribution will give a historical overview of these two research eras, taking advantage of the archives conserved at Institut Pasteur. The first era mainly focused on the production, characterisation, surveillance and improvement of veterinary anthrax vaccines; the concepts and technologies with which to reach a deep understanding of this research field were not yet available.

[Unconventional Laveran].

Charles Louis Alphonse Laveran - 18 June 1845 - 18 May 1922: first French Nobel Prize in Medicine, "in recognition of his work on the role played by protozoa in causing diseases". One hundred years after his death, only written records remain of his work and life. The witnesses to this period are no more.

Early expression of capsule during Bacillus anthracis germination.

Bacillus anthracis is a spore-forming bacterium that produces two major virulence factors, a tripartite toxin with two enzymatic toxic activities and a pseudo-proteic capsule. One of the main described functions of the poly-gamma-d-glutamate capsule is to enable B. anthracis bacilli to escape phagocytosis.

Management and characteristics of patients suffering from infection in primary care.

Background: infection (CDI) is rising and increases patient healthcare costs due to extended hospitalisation, tests and medications. Management of CDI in French primary care is poorly reported.

Objectives: To characterise patients suffering from CDI, managed in primary care and describe their clinical outcomes.

Analyzing the Relationship Between the Activation of the Edema Factor and Its Interaction With Calmodulin.

Molecular dynamics (MD) simulations have been recorded on the complex between the edema factor (EF) of and calmodulin (CaM), starting from a structure with the orthosteric inhibitor adefovir bound in the EF catalytic site. The starting structure has been destabilized by alternately suppressing different co-factors, such as adefovir ligand or ions, revealing several long-distance correlations between the conformation of CaM, the geometry of the CaM/EF interface, the enzymatic site and the overall organization of the complex. An allosteric communication between CaM/EF interface and the EF catalytic site, highlighted by these correlations, was confirmed by several bioinformatics approaches from the literature.

Very Early Blood Diffusion of the Active Lethal and Edema Factors of Bacillus anthracis After Intranasal Infection.

Background: 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.

Methods: To investigate the diffusion of edema factor (EF) and lethal factor (LF), 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.

Questionable Efficacy of Therapeutic Antibodies in the Treatment of Anthrax.

Inhalational anthrax caused by , a spore-forming Gram-positive bacterium, is a highly lethal infection. Antibodies targeting the protective antigen (PA) binding component of the toxins have recently been authorized as an adjunct to antibiotics, although no conclusive evidence demonstrates that anthrax antitoxin therapy has any significant benefit. We discuss here the rational basis of anti-PA development regarding the pathogenesis of the disease.

Corrigendum: Heterogeneous Family of Cyclomodulins: Smart Weapons That Allow Bacteria to Hijack the Eukaryotic Cell Cycle and Promote Infections.

[This corrects the article on p. 208 in vol. 7, PMID: 28589102.

Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on the bactericidal activity of membrane active oligourea foldamers.

Membrane-active foldamers have recently emerged as potential mimics of antimicrobial peptides (AMPs). Amphiphilic cationic helical N,N'-linked oligoureas are one such class of AMP mimics with activities in vitro against a broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating bacillus and causing agent of anthrax. Here we have used site-selective chemical modifications of the oligourea backbone to gain additional insight into the relationship between structure and function and modulate anthracidal activity.

Heterogeneous Family of Cyclomodulins: Smart Weapons That Allow Bacteria to Hijack the Eukaryotic Cell Cycle and Promote Infections.

Some bacterial pathogens modulate signaling pathways of eukaryotic cells in order to subvert the host response for their own benefit, leading to successful colonization and invasion. Pathogenic bacteria produce multiple compounds that generate favorable conditions to their survival and growth during infection in eukaryotic hosts. Many bacterial toxins can alter the cell cycle progression of host cells, impairing essential cellular functions and impeding host cell division.

Mechanisms of Invariant NKT Cell Activity in Restraining Bacillus anthracis Systemic Dissemination.

Exogenous activation of invariant NKT (iNKT) cells by the superagonist α-galactosylceramide (α-GalCer) can protect against cancer, autoimmune diseases, and infections. In the current study, we investigated the effect of α-GalCer against Bacillus anthracis infection, the agent of anthrax. Using an experimental model of s.

Proteolytically Stable Foldamer Mimics of Host-Defense Peptides with Protective Activities in a Murine Model of Bacterial Infection.

The synthesis of bioinspired unnatural backbones leading to foldamers can provide effective peptide mimics with improved properties in a physiological environment. This approach has been applied to the design of structural mimics of membrane active antimicrobial peptides (AMPs) for which activities in vitro have been reported. Yet activities and pharmacokinetic properties in vivo in animal models have remained largely unexplored.

In vivo dynamics of active edema and lethal factors during anthrax.

Lethal and edema toxins are critical virulence factors of Bacillus anthracis. However, little is known about their in vivo dynamics of production during anthrax. In this study, we unraveled for the first time the in vivo kinetics of production of the toxin components EF (edema factor) and LF (lethal factor) during cutaneous infection with a wild-type toxinogenic encapsulated strain in immuno-competent mice.

Physical Sequestration of Bacillus anthracis in the Pulmonary Capillaries in Terminal Infection.

The lung is the terminal target of Bacillus anthracis before death, whatever the route of infection (cutaneous, inhalational, or digestive). During a cutaneous infection in absence of toxins, we observed encapsulated bacteria colonizing the alveolar capillary network, bacteria and hemorrhages in alveolar and bronchiolar spaces, and hypoxic foci in the lung (endothelial cells) and brain (neurons and neuropil). Circulating encapsulated bacteria were as chains of approximately 13 µm in length.

Crossing of the epithelial barriers by Bacillus anthracis: the Known and the Unknown.

Anthrax, caused by Bacillus anthracis, a Gram-positive spore-forming bacterium, is initiated by the entry of spores into the host body. There are three types of human infection: cutaneous, inhalational, and gastrointestinal. For each form, B.

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.

Capsules, toxins and AtxA as virulence factors of emerging Bacillus cereus biovar anthracis.

Emerging B. cereus strains that cause anthrax-like disease have been isolated in Cameroon (CA strain) and Côte d'Ivoire (CI strain). These strains are unusual, because their genomic characterisation shows that they belong to the B.

Identification and validation of specific markers of Bacillus anthracis spores by proteomics and genomics approaches.

Bacillus anthracis is the causative bacteria of anthrax, an acute and often fatal disease in humans. The infectious agent, the spore, represents a real bioterrorism threat and its specific identification is crucial. However, because of the high genomic relatedness within the Bacillus cereus group, it is still a real challenge to identify B.

In vivo germination of Bacillus anthracis spores during murine cutaneous infection.

Background: Germination is a key step for successful Bacillus anthracis colonization and systemic dissemination. Few data are available on spore germination in vivo, and the necessity of spore and host cell interactions to initiate germination is unclear.

Methods: To investigate the early interactions between B.

Cell-wall preparation containing poly-γ-D-glutamate covalently linked to peptidoglycan, a straightforward extractable molecule, protects mice against experimental anthrax infection.

Bacillus anthracis is the causative agent of anthrax that is characterized by septicemia and toxemia. Many vaccine strategies were described to counteract anthrax infection. In contrast with veterinary live vaccines, currently human vaccines are acellular with the protective antigen, a toxin component, as the main constituent.

Mechanisms of NK cell-macrophage Bacillus anthracis crosstalk: a balance between stimulation by spores and differential disruption by toxins.

NK cells are important immune effectors for preventing microbial invasion and dissemination, through natural cytotoxicity and cytokine secretion. Bacillus anthracis spores can efficiently drive IFN-γ production by NK cells. The present study provides insights into the mechanisms of cytokine and cellular signaling that underlie the process of NK-cell activation by B.

cAMP signaling by anthrax edema toxin induces transendothelial cell tunnels, which are resealed by MIM via Arp2/3-driven actin polymerization.

RhoA-inhibitory bacterial toxins, such as Staphylococcus aureus EDIN toxin, induce large transendothelial cell macroaperture (TEM) tunnels that rupture the host endothelium barrier and promote bacterial dissemination. Host cells repair these tunnels by extending actin-rich membrane waves from the TEM edges. We reveal that cyclic-AMP signaling produced by Bacillus anthracis edema toxin (ET) also induces TEM formation, which correlates with increased vascular permeability.