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

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

Genetic evidence for a protective role of the peritrophic matrix against intestinal bacterial infection in Drosophila melanogaster

The peritrophic matrix (PM) forms a layer composed of chitin and glycoproteins that lines the insect intestinal lumen. This physical barrier plays a role analogous to that of mucous secretions of the vertebrate digestive tract and is thought to protect the midgut epithelium from abrasive food particles and microbes. Almost nothing is known about PM functions in Drosophila, and its function as an immune barrier has never been addressed by a genetic approach. Here we show that the Drosocrystallin (Dcy) protein, a putative component of the eye lens of Drosophila, contributes to adult PM formation. A loss-of-function mutation in the dcy gene results in a reduction of PM width and an increase of its permeability. Upon bacterial ingestion a higher level of expression of antibacterial peptides was observed in dcy mutants, pointing to an influence of this matrix on bacteria sensing by the Imd immune pathway. Moreover, dcy-deficient flies show an increased susceptibility to oral infections with the entomopathogenic bacteria Pseudomonas entomophila and Serratia marcescens. Dcy mutant flies also succumb faster than wild type upon ingestion of a P. entomophila toxic extract. We show that this lethality is due in part to an increased deleterious action of Monalysin, a pore-forming toxin produced by P. entomophila. Collectively, our analysis of the dcy immune phenotype indicates that the PM plays an important role in Drosophila host defense against enteric pathogens, preventing the damaging action of pore-forming toxins on intestinal cells

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

A secondary metabolite acting as a signalling molecule controls Pseudomonas entomophila virulence

Pseudomonas entomophila is an entomopathogenic bacterium that is lethal to Drosophila melanogaster within 1-2 days of ingestion of high doses. Flies orally infected with P. entomophila rapidly succumb despite the induction of both local and systemic immune responses. Recent studies suggest that its virulence relies on its ability to cause irreversible damages to the intestinal epithelium, in contrast to what is observed with milder pathogenic bacteria such as Erwinia carotovora carotovora Ecc15 or Pseudomonas aeruginosa PA14. The GacS/GacA two-component system plays a key role in P. entomophila pathogenicity. Here, we report the identification of the pvf genes, whose products are involved in production of a secondary metabolite involved in P. entomophila virulence. A pvf mutant is impaired in its ability to persist within the gut, to trigger the fly immune responses and to inflict gut damages. The expression of several genes is affected in a pvf mutant, independently of the Gac system. Moreover, growing a pvf mutant in medium supplemented with supernatant extracts from either the wild-type strain or a gacA mutant restore its pathogenicity. Collectively, our results indicate that we identified genes involved in the synthesis of a signalling molecule that controls P. entomophila virulence independently from the Gac system

Tularemia on the rise in Switzerland? A one health approach is needed!

In the last 10 years, an increase in tularemia cases has been observed in both humans and animals in Switzerland. In these, infection with Francisella tularensis, the causative agent of the zoonotic disease tularemia, can occur through arthropod vectors or contact to infected animals or exposure to contaminated environmental sources. Currently, we are only able to postulate potential aetiologies: (i) behavioral changes of humans with more exposure to endemic habitats of infected arthropod vectors; (ii) an increased rate of tularemia infected ticks; (iii) increasing number and geographical regions of tick biotopes; (iv) increasing and/or more diverse reservoir populations; (v) increasing presence of bacteria in the environment; (vi) raised awareness and increased testing among physicians; (vii) improved laboratory techniques including molecular testing. To approach these questions, a one-health strategy is necessary. A functioning collaboration between public health, human medicine, and diagnostic and veterinary units for the control of tularemia must be established. Furthermore, the public should be included within citizen-supported-science-projects

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