Révolution dans le monde de la Tuberculose

Cette étude a démontré la possibilité d'utiliser le GeneXpert MTB/RIF, non seulement pour le diagnostic initial de la tuberculose, mais surtout pour évaluer le potentiel de transmission de la maladie des patients tuberculeux. Elle a permis d’introduire pour la première fois un algorithme clinique et microbiologique de prise en charge des patients avec suspicion de tuberculose dans lequel le GeneXpert remplace la détection de BAAR par examen direct pour initier le dia-gnostique microbiologique. Ce changement diagnostique, qui sonne comme une révolution dans le monde de la tuberculose, est une valeur ajoutée indéniable en termes de gestion de flux de patients, de leur prise en charge clinique et de l’organisation du laboratoire de microbiologie

Pseudomonas entomophila: A Versatile Bacterium with Entomopathogenic Properties

Pseudomonas entomophila is unique among Pseudomonas species in being able to activate a systemic immune response in both Drosophila larvae and adults. It has been subsequently shown that oral infections with high doses of this bacterium are highly pathogenic to Drosophila and cause massive destruction of the Drosophila gut epithelium. Besides Drosophila, P. entomophila was able to kill other insects from at least three different orders, suggesting that it has a potentially wide host range and making it a promising model for the study of host pathogen interactions and for the development of bio-control agents against insect pests. In order to unravel the features contributing to P. entomophila’s pathogenic properties, its complete genome was sequenced and genetic screens were performed to identify virulence factors encoded by this bacterium. The aim of this chapter is to review the current knowledge we have on this bacterium with a particular focus on the pathogenesis it induces, its virulence effectors and their genetic regulatio

Editorial: Tuberculosis and non-tuberculous mycobacteria infections: control, diagnosis and treatment

Tuberculosis (TB), is one of the top 10 causes of death worldwide (WHO). According to the last Global TB report from the World Health Organization, 10 million persons were estimated to have had TB in 2019 worldwide, causing about 1.6 million deaths. Tuberculosis has not only a dramatic impact on the quality of life for the patients, but also has raised many socio-economic issues at a community level, especially in medium and high burden regions, such as India, China, and Indonesia. In 2014, WHO adopted the "End TB strategy" which aimed to reduce TB deaths by 90% between 2015 and 2030, to prevent new cases by 80% during the same period and to decrease the socioeconomic impact of the disease at a family level. Even though tuberculosis global incidence has decreased significantly, efforts still need to be made to reach these goals. Non-tuberculous mycobacteria (NTM), in contrast to Mycobacterium tuberculosis, are bacteria widely spread in the environment and can be found in a broad range of ecosystems such as soils and water, including drinking water systems. NTM are opportunistic pathogens associated with both pulmonary and extrapulmonary infections. This Research Topic collected articles addressing: (i) TB and NTMs associated diseases, diagnostic, control, and public health, (ii) mycobacterial genomics, (iii) and antimycobacterial drugs and resistanc

Molecular and Mass Spectrometry Detection and Identification of Causative Agents of Bloodstream Infections

Bloodstream infections (BSIs) are severe diseases associated with a high morbidity and mortality, which increases with the delay until administration of the first appropriate antibiotic (1–8). For this reason, empiric treatments made of broad-range anti-infectious compounds or made of a combination of antimicrobials are started immediately after the sampling of blood bottles. BSIs can be caused by various microorganisms. In the absence of microbiological documentation, physicians suspect a BSI on the basis of clinical symptoms, which trigger the start of empirical treatments. The clinical presentations are multiple and include fever or hypothermia, increases in heart rate, change in inflammatory variable (C-reactive protein, procalcitonin, and white blood cell count increase), and organ failure (2, 9). These symptoms are generally nonspecific and only suggest bloodstream dissemination. Empirical treatments are made of broad-spectrum antibiotics on the basis of the clinical and epidemiological data, but this does not exclude any risk of inappropriate initial treatment

Interseasonal RSV infections in Switzerland - rapid establishment of a clinician-led national reporting system (RSV EpiCH).

In anticipation of an interseasonal respiratory syncytial virus (RSV) epidemic, a clinician-led reporting system was rapidly established to capture RSV infections in Swiss hospitals, starting in January 2021. Here, we present details of the reporting system and first results to June 2021. An unusual epidemiology was observed with an interseasonal surge of RSV infections associated with COVID-19-related non-pharmacological interventions. These data allowed real-time adjustment of RSV prophylaxis guidelines and consequently underscore the need for and continuation of systematic nationwide RSV surveillance

SARS-CoV-2 N501Y Introductions and Transmissions in Switzerland from Beginning of October 2020 to February 2021—Implementation of Swiss-Wide Diagnostic Screening and Whole Genome Sequencing

The rapid spread of the SARS-CoV-2 lineages B.1.1.7 (N501Y.V1) throughout the UK, B.1.351 (N501Y.V2) in South Africa, and P.1 (B.1.1.28.1; N501Y.V3) in Brazil has led to the definition of variants of concern (VoCs) and recommendations for lineage specific surveillance. In Switzerland, during the last weeks of December 2020, we established a nationwide screening protocol across multiple laboratories, focusing first on epidemiological and microbiological definitions. In January 2021, we validated and implemented an N501Y-specific PCR to rapidly screen for VoCs, which are then confirmed using amplicon sequencing or whole genome sequencing (WGS). A total of 13,387 VoCs have been identified since the detection of the first Swiss case in October 2020, with 4194 being B.1.1.7, 172 B.1.351, and 7 P.1. The remaining 9014 cases of VoCs have been described without further lineage specification. Overall, all diagnostic centers reported a rapid increase of the percentage of detected VOCs, with a range of 6 to 46% between 25 to 31 of January 2021 increasing towards 41 to 82% between 22 to 28 of February. A total of 739 N501Y positive genomes were analysed and show a broad range of introduction events to Switzerland. In this paper, we describe the nationwide coordination and implementation process across laboratories, public health institutions, and researchers, the first results of our N501Y-specific variant screening, and the phylogenetic analysis of all available WGS data in Switzerland, that together identified the early introduction events and subsequent community spreading of the VoCs

Bacillus sphaericus Binary Toxin Elicits Host Cell Autophagy as a Response to Intoxication

Bacillus sphaericus strains that produce the binary toxin (Bin) are highly toxic to Culex and Anopheles mosquitoes, and have been used since the late 1980s as a biopesticide for the control of these vectors of infectious disease agents. The Bin toxin produced by these strains targets mosquito larval midgut epithelial cells where it binds to Cpm1 (Culex pipiens maltase 1) a digestive enzyme, and causes severe intracellular damage, including a dramatic cytoplasmic vacuolation. The intoxication of mammalian epithelial MDCK cells engineered to express Cpm1 mimics the cytopathologies observed in mosquito enterocytes following Bin ingestion: pore formation and vacuolation. In this study we demonstrate that Bin-induced vacuolisation is a transient phenomenon that affects autolysosomes. In addition, we show that this vacuolisation is associated with induction of autophagy in intoxicated cells. Furthermore, we report that after internalization, Bin reaches the recycling endosomes but is not localized either within the vacuolating autolysosomes or within any other degradative compartment. Our observations reveal that Bin elicits autophagy as the cell's response to intoxication while protecting itself from degradation through trafficking towards the recycling pathways

Monalysin, a Novel ß-Pore-Forming Toxin from the Drosophila Pathogen Pseudomonas entomophila, Contributes to Host Intestinal Damage and Lethality

Pseudomonas entomophila is an entomopathogenic bacterium that infects and kills Drosophila. P. entomophila pathogenicity is linked to its ability to cause irreversible damages to the Drosophila gut, preventing epithelium renewal and repair. Here we report the identification of a novel pore-forming toxin (PFT), Monalysin, which contributes to the virulence of P. entomophila against Drosophila. Our data show that Monalysin requires N-terminal cleavage to become fully active, forms oligomers in vitro, and induces pore-formation in artificial lipid membranes. The prediction of the secondary structure of the membrane-spanning domain indicates that Monalysin is a PFT of the ß-type. The expression of Monalysin is regulated by both the GacS/GacA two-component system and the Pvf regulator, two signaling systems that control P. entomophila pathogenicity. In addition, AprA, a metallo-protease secreted by P. entomophila, can induce the rapid cleavage of pro-Monalysin into its active form. Reduced cell death is observed upon infection with a mutant deficient in Monalysin production showing that Monalysin plays a role in P. entomophila ability to induce intestinal cell damages, which is consistent with its activity as a PFT. Our study together with the well-established action of Bacillus thuringiensis Cry toxins suggests that production of PFTs is a common strategy of entomopathogens to disrupt insect gut homeostasis

External quality assessment of SARS-CoV-2-sequencing: An ESGMD-SSM pilot trial across 15 European laboratories

Objective: This first pilot on external quality assessment (EQA) of SARS-CoV-2 whole genome sequencing, initiated by the ESCMID Study Group for Genomic and Molecular Diagnostics (ESGMD) and Swiss Society for Microbiology (SSM), aims to build a framework between laboratories in order to improve pathogen surveillance sequencing.Methods: Ten samples with varying viral loads were sent out to 15 clinical laboratories who had free choice of sequencing methods and bioinformatic analyses. The key aspects on which the individual centres were compared on were identification of 1) SNPs and indels, 2) Pango lineages, and 3) clusters between samples.Results: The participating laboratories used a wide array of methods and analysis pipelines. Most were able to generate whole genomes for all samples. Genomes were sequenced to varying depth (up to 100-fold difference across centres). There was a very good consensus regarding the majority of reporting criteria, but there were a few discrepancies in lineage and cluster assignment. Additionally, there were inconsistencies in variant calling. The main reasons for discrepancies were missing data, bioinformatic choices, and interpretation of data.Conclusions: The pilot EQA was an overall success. It was able to show the high quality of participating labs and provide valuable feedback in cases where problems occurred, thereby improving the sequencing setup of laboratories. A larger follow-up EQA should, however, improve on defining the variables and format of the report. Additionally, contamination and/or minority variants should be a further aspect of assessment.</p