We will be serving as the Guest Editor for this very interesting Special Issue on "Non-Invasive Device-Mediated Drug Delivery to the Brain Across the Blood-Brain Barrier" ....
Abstract
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.
Results
One hour after mouse challenge, although only 7% of mice presented bacteremia, LF and EF were detected in the blood of 100% and 42% of mice, respectively. Protective antigen 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.
Conclusions
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 enzymatically active components of B anthracis toxins and bacteria can diffuse very early in the blood during inhalational anthrax model, paving the way for an ultra-precocious diagnosis and the setup of an early and effective treatment.
Contamination with microorganisms occurs in laboratories but is also of high concern in the context of bioterrorism. Decontamination is a cornerstone that promotes good laboratory practices and ...occupational health and safety. Among the most resistant structures formed by microorganisms are spores, produced notably by Clostridium and Bacillus species. Here, we compared six products containing four different molecules (sodium hypochlorite, hydrogen peroxide, peracetic acid, and calcium hypochlorite) on B. anthracis Sterne spores. We first selected the most efficient product based on its activity against spore suspensions using French and European standards. Four products showed sporicidal activity, of which only two did so in a time frame consistent with good laboratory practices. Then, we tested one of these two products under laboratory conditions on fully virulent B. anthracis spores, during common use and after contamination through a spill of a highly concentrated spore suspension. We, thus, robustly validated a decontaminant based on calcium hypochlorite not only on its ability to kill spores but also on its effectiveness under laboratory conditions. At the end, we were able to assure a complete disinfection in 1 minute after spillover and in 2 minutes for common use.
Abstract
Background
On May 6, 2022, a powerful outbreak of monkeypox virus (MPXV) had been reported outside of Africa, with many continuing new cases being reported around the world. Analysis of ...mutations among the 2 different lineages present in the 2021 and 2022 outbreaks revealed the presence of G->A mutations occurring in the 5′GpA context, indicative of APOBEC3 cytidine deaminase activity.
Methods
By using a sensitive polymerase chain reaction (differential DNA denaturation PCR) method allowing differential amplification of AT-rich DNA, we analyzed the level of APOBEC3-induced MPXV editing in infected cells and in patients.
Results
We demonstrate that G->A hypermutated MPXV genomes can be recovered experimentally from APOBEC3 transfection followed by MPXV infection. Here, among the 7 human APOBEC3 cytidine deaminases (A3A-A3C, A3DE, A3F–A3H), only APOBEC3F was capable of extensively deaminating cytidine residues in MPXV genomes. Hyperedited genomes were also recovered in ∼42% of analyzed patients. Moreover, we demonstrate that substantial repair of these mutations occurs. Upon selection, corrected G->A mutations escaping drift loss contribute to the MPXV evolution observed in the current epidemic.
Conclusions
Stochastic or transient overexpression of the APOBEC3F gene exposes the MPXV genome to a broad spectrum of mutations that may be modeling the mutational landscape after multiple cycles of viral replication.
We analyzed the level of APOBEC3-induced MPXV editing in infected cells and in patients. We demonstrated that G->A hypermutated MPXV genomes can be recovered from APOBEC3F transfection followed by MPXV infection. Hyperedited genomes were also recovered in ∼42% of patients.
The eradication of infectious diseases has been achieved only once in history, in 1980, with smallpox. Since 1988, significant effort has been made to eliminate poliomyelitis viruses, but eradication ...is still just out of reach. As the goal of viral disease eradication approaches, the ability to recreate historically eradicated viruses using synthetic biology has the potential to jeopardize the long-term sustainability of eradication. However, the emergence of the severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 pandemic has highlighted our ability to swiftly and resolutely respond to a potential outbreak. This virus has been synthetized faster than any other in the past and is resulting in vaccines before most attenuated candidates reach clinical trials. Here, synthetic biology has the opportunity to demonstrate its truest potential to the public and solidify a footing in the world of vaccines.
In vivo microscopy has recently become a gold standard in lung immunology studies involving small animals, largely benefiting from the democratization of multiphoton microscopy allowing for deep ...tissue imaging. This technology represents currently our only way of exploring the lungs and inferring what happens in human respiratory medicine. The interest of lung in vivo microscopy essentially relies upon its relevance as a study model, fulfilling physiological requirements in comparison with in vitro and ex vivo experiments. However, strategies developed in order to overcome movements of the thorax caused by breathing and heartbeats remain the chief drawback of the technique and a major source of invasiveness. In this context, minimizing invasiveness is an unavoidable prerequisite for any improvement of lung in vivo microscopy. This review puts into perspective the main techniques enabling lung in vivo microscopy, providing pros and cons regarding invasiveness.
In vivo microscopy of the lungs in small laboratory animals greatly suffers from movements coming from both breathing and a beating heart. In order to overcome this pitfall, existing techniques often rely on highly invasive procedures, which are likely to produce unsolicited reactions eventually leading to biased results. This review examines these techniques, putting into perspective their pros and cons regarding invasiveness as well as recently described approaches helping to reduce it.
Inflammatory lesions after Influenza A viruses (IAV) are potential therapeutic target for which better understanding of post-infection immune mechanisms is required. Most studies to evaluate innate ...immune reactions induced by IAV are based on quantitative/functional methods and anatomical exploration is most often non-existent. We aimed to study pulmonary damage and macrophage recruitment using two-photon excitation microscopy (TPEM) after IAV infection.
We infected C57BL/6 CD11c
YFP mice with A/Puerto Ricco/8/34 H1N1. We performed immune cell analysis, including flow cytometry, cytokine concentration assays, and TPEM observations after staining with anti-F4/80 antibody coupled to BV421. We adapted live lung slice (LLS) method for
intravital microscopy to analyze cell motility.
TPEM provided complementary data to flow cytometry and cytokine assays by allowing observation of bronchial epithelium lesions and spreading of local infection. Addition of F4/80-BV421 staining allowed us to precisely determine timing of recruitment and pulmonary migration of macrophages.
LLS preserved cellular viability, allowing us to observe acceleration of macrophage motility.
After IAV infection, we were able to explore structural consequences and successive waves of innate immune cell recruitment. By combining microscopy, flow cytometry and chemokine measurements, we describe novel and precise scenario of innate immune response against IAV.
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