Two-year clinico-biological feedback in Overseas France and French-speaking territories during Covid-19 pandemic / Retour d'expériences clinico-biologiques en Outre-mer et en Francophonie après deux années de pandémie Covid-19

The French Society of Clinical Biology (SFBC) set up a working group "Biochemical markers of Covid-19" whose main objective is to review, analyse and monitor biological prescriptions according to the patient's care path. This study covers all public and private sectors of medical biology in metropolitan France and overseas and extends to the French-speaking world. We present a summary of feedbacks after 2 years of the pandemic. At the early stage of Covid-19, with regard to the regions surveyed, a common symptomatology with local zoonosis (dengue fever, zika, malaria, leptospirosis, etc.) complicates the diagnosis of Covid-19. At a more advanced stage, it is a question of managing an influx of patients suffering from acute respiratory distress syndrome. In this case, the biology is then simpler and delocalized medical biology devices have proven their effectiveness. As a result, ICU clinicians can better manage the frequent comorbidities encountered in these regions: obesity, diabetes, chronic renal failure, cardiovascular diseases.

La Société française de biologie clinique (SFBC) a mis en place un groupe de travail « Marqueurs biochimiques de Covid-19 ¼ dont l'objectif principal est de revoir, d'analyser et de suivre les prescriptions biologiques en fonction du parcours de soins du patient. Cette étude couvre tous les secteurs publics et privés de la biologie médicale en métropole et en Outre-mer et s'étend à la Francophonie. Nous présentons une synthèse des retours d'expériences après 2 ans de pandémie. Au stade précoce de la Covid-19, pour les régions interrogées, une symptomatologie commune avec des zoonoses locales (dengue, zika, paludisme, leptospirose…) complique le diagnostic de la Covid-19. À un stade plus avancé, il s'agit de gérer un afflux de patients atteints de syndrome de détresse respiratoire aiguë. La biologie est alors plus simple, et les dispositifs de biologie médicale délocalisée ont prouvé leur efficacité. De ce fait, les réanimateurs peuvent mieux gérer les comorbidités fréquentes rencontrées dans ces régions : obésité, diabète, insuffisance rénale chronique ou maladies cardiovasculaires.

[Management of a global health crisis: first COVID-19 disease feedback from Overseas and French-speaking countries medical biologists]. / Gestion d'une crise sanitaire mondiale : premiers retours d'expérience de biologistes médicaux d'Outre-mer et de francophonie face au COVID-19.

The French society of clinical biology "Biochemical markers of COVID-19" has set up a working group with the primary aim of reviewing, analyzing and monitoring the evolution of biological prescriptions according to the patient's care path and to look for markers of progression and severity of the disease. This study covers all public and private sectors of medical biology located in metropolitan and overseas France and also extends to the French-speaking world. This article presents the testimonies and data obtained for the "Overseas and French-speaking countries" sub-working group made up of 45 volunteer correspondents, located in 20 regions of the world. In view of the delayed spread of the SARS-CoV-2 virus, the overseas regions and the French-speaking regions have benefited from feedback from the first territories confronted with COVID-19. Thus, the entry of the virus or its spread in epidemic form could be avoided, thanks to the rapid closure of borders. The overseas territories depend very strongly on air and/or sea links with the metropolis or with the neighboring continent. The isolation of these countries is responsible for reagent supply difficulties and has necessitated emergency orders and the establishment of stocks lasting several months, in order to avoid shortages and maintain adequate patient care. In addition, in countries located in tropical or intertropical zones, the diagnosis of COVID-19 is complicated by the presence of various zoonoses (dengue, Zika, malaria, leptospirosis, etc.).

The final assembly of trehalose polyphleates takes place within the outer layer of the mycobacterial cell envelope.

Trehalose polyphleates (TPP) are high-molecular-weight, surface-exposed glycolipids present in a broad range of nontuberculous mycobacteria. These compounds consist of a trehalose core bearing polyunsaturated fatty acyl substituents (called phleic acids) and a straight-chain fatty acid residue and share a common basic structure with trehalose-based glycolipids produced by Mycobacterium tuberculosis TPP production starts in the cytosol with the formation of a diacyltrehalose intermediate. An acyltransferase, called PE, subsequently catalyzes the transfer of phleic acids onto diacyltrehalose to form TPP, and an MmpL transporter promotes the export of TPP or its precursor across the plasma membrane. PE is predicted to be an anchored membrane protein, but its topological organization is unknown, raising questions about the subcellular localization of the final stage of TPP biosynthesis and the chemical nature of the substrates that are translocated by the MmpL transporter. Here, using genetic, biochemical, and proteomic approaches, we established that PE of Mycobacterium smegmatis is exported to the cell envelope following cleavage of its signal peptide and that this process is required for TPP biosynthesis, indicating that the last step of TPP formation occurs in the outer layers of the mycobacterial cell envelope. These results provide detailed insights into the molecular mechanisms controlling TPP formation and transport to the cell surface, enabling us to propose an updated model of the TPP biosynthetic pathway. Because the molecular mechanisms of glycolipid production are conserved among mycobacteria, these findings obtained with PE from M. smegmatis may offer clues to glycolipid formation in M. tuberculosis.

Dissecting the mycobacterial cell envelope and defining the composition of the native mycomembrane.

The mycobacterial envelope is unique, containing the so-called mycomembrane (MM) composed of very-long chain fatty acids, mycolic acids (MA). Presently, the molecular composition of the MM remains unproven, due to the diversity of methods used for determining its composition. The plasma membranes (PM) and the native MM-containing cell walls (MMCW) of two rapid-growing mycobacterial species, Mycobacterium aurum and M. smegmatis, were isolated from their cell lysates by differential ultracentrifugation. Transmission electron microscopy and biochemical analyses demonstrated that the two membranes were virtually pure. Bottom-up quantitative proteomics study indicated a different distribution of more than 2,100 proteins between the PM and MMCW. Among these, the mannosyltransferase PimB, galactofuranosyltransferase GlfT2, Cytochrome p450 and ABC transporter YjfF, were most abundant in the PM, which also contain lipoglycans, phospholipids, including phosphatidylinositol mannosides, and only a tiny amount of other glycolipids. Antigen85 complex proteins, porins and the putative transporters MCE protein family were mostly found in MMCW fraction that contains MA esterifying arabinogalactan, constituting the inner leaflet of MM. Glycolipids, phospholipids and lipoglycans, together with proteins, presumably composed the outer leaflet of the MM, a lipid composition that differs from that deduced from the widely used extraction method of mycobacterial cells with dioctylsulfosuccinate sodium.