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      Lipoarabinomannan as a Point-of-Care Assay for Diagnosis of Tuberculosis: How Far Are We to Use It?

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          Abstract

          Tuberculosis (TB) is still a severe public health problem; the current diagnostic tests have limitations that delay treatment onset. Lipoarabinomannan (LAM) is a glycolipid that is a component of the cell wall of the bacillus Mycobacterium tuberculosis, the etiologic agent of TB. This glycolipid is excreted as a soluble form in urine. The World Health Organization has established that the design of new TB diagnostic methods is one of the priorities within the EndTB Strategy. LAM has been suggested as a biomarker to develop diagnostic tests based on its identification in urine, and it is one of the most prominent candidates to develop point-of-care diagnostic test because urine samples can be easily collected. Moreover, LAM can regulate the immune response in the host and can be found in the serum of TB patients, where it probably affects a wide variety of host cell populations, consequently influencing the quality of both innate and adaptive immune responses during TB infection. Here, we revised the evidence that supports that LAM could be used as a tool for the development of new point-of-care tests for TB diagnosis, and we discussed the mechanisms that could contribute to the low sensitivity of diagnostic testing.

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          Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.

          Countless millions of people have died from tuberculosis, a chronic infectious disease caused by the tubercle bacillus. The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analysed in order to improve our understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions. The genome comprises 4,411,529 base pairs, contains around 4,000 genes, and has a very high guanine + cytosine content that is reflected in the biased amino-acid content of the proteins. M. tuberculosis differs radically from other bacteria in that a very large portion of its coding capacity is devoted to the production of enzymes involved in lipogenesis and lipolysis, and to two new families of glycine-rich proteins with a repetitive structure that may represent a source of antigenic variation.
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            Bacterial membrane lipids: diversity in structures and pathways.

            For many decades, Escherichia coli was the main model organism for the study of bacterial membrane lipids. The results obtained served as a blueprint for membrane lipid biochemistry, but it is clear now that there is no such thing as a typical bacterial membrane lipid composition. Different bacterial species display different membrane compositions and even the membrane composition of cells belonging to a single species is not constant, but depends on the environmental conditions to which the cells are exposed. Bacterial membranes present a large diversity of amphiphilic lipids, including the common phospholipids phosphatidylglycerol, phosphatidylethanolamine and cardiolipin, the less frequent phospholipids phosphatidylcholine, and phosphatidylinositol and a variety of other membrane lipids, such as for example ornithine lipids, glycolipids, sphingolipids or hopanoids among others. In this review, we give an overview about the membrane lipid structures known in bacteria, the different metabolic pathways involved in their formation, and the distribution of membrane lipids and metabolic pathways across taxonomical groups.
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              Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection.

              SUMMARYTuberculosis (TB) is the leading infectious cause of mortality worldwide, due in part to a limited understanding of its clinical pathogenic spectrum of infection and disease. Historically, scientific research, diagnostic testing, and drug treatment have focused on addressing one of two disease states: latent TB infection or active TB disease. Recent research has clearly demonstrated that human TB infection, from latent infection to active disease, exists within a continuous spectrum of metabolic bacterial activity and antagonistic immunological responses. This revised understanding leads us to propose two additional clinical states: incipient and subclinical TB. The recognition of incipient and subclinical TB, which helps divide latent and active TB along the clinical disease spectrum, provides opportunities for the development of diagnostic and therapeutic interventions to prevent progression to active TB disease and transmission of TB bacilli. In this report, we review the current understanding of the pathogenesis, immunology, clinical epidemiology, diagnosis, treatment, and prevention of both incipient and subclinical TB, two emerging clinical states of an ancient bacterium.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                15 April 2021
                2021
                : 12
                : 638047
                Affiliations
                [1] 1Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas , Mexico City, Mexico
                [2] 2Laboratory of Immunomicrobiology, Department of Microbiology, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional , Mexico City, Mexico
                Author notes

                Edited by: Pranabashis Haldar, University of Leicester, United Kingdom

                Reviewed by: Shibali Das, Washington University School of Medicine in St. Louis, United States; Gerald Larrouy-Maumus, Imperial College London, United Kingdom

                *Correspondence: Leslie Chavez-Galan, lchavez_galan@ 123456iner.gob.mx

                This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2021.638047
                8081860
                33935997
                5dbcd361-ac65-4eaa-9869-54a53f8dc7a2
                Copyright © 2021 Flores, Cancino and Chavez-Galan.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 December 2020
                : 22 March 2021
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 153, Pages: 16, Words: 14569
                Categories
                Microbiology
                Review

                Microbiology & Virology
                lipoarabinomannan,tuberculosis,point-of-care assay,immune response,immunoregulation

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