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      Mycoplasma pneumoniae Infections: Pathogenesis and Vaccine Development

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          Abstract

          Mycoplasma pneumoniae is a major causative agent of community-acquired pneumonia which can lead to both acute upper and lower respiratory tract inflammation, and extrapulmonary syndromes. Refractory pneumonia caused by M. pneumonia can be life-threatening, especially in infants and the elderly. Here, based on a comprehensive review of the scientific literature related to the respective area, we summarize the virulence factors of M. pneumoniae and the major pathogenic mechanisms mediated by the pathogen: adhesion to host cells, direct cytotoxicity against host cells, inflammatory response-induced immune injury, and immune evasion. The increasing rate of macrolide-resistant strains and the harmful side effects of other sensitive antibiotics (e.g., respiratory quinolones and tetracyclines) in young children make it difficult to treat, and increase the health risk or re-infections. Hence, there is an urgent need for development of an effective vaccine to prevent M. pneumoniae infections in children. Various types of M. pneumoniae vaccines have been reported, including whole-cell vaccines (inactivated and live-attenuated vaccines), subunit vaccines (involving M. pneumoniae protein P1, protein P30, protein P116 and CARDS toxin) and DNA vaccines. This narrative review summarizes the key pathogenic mechanisms underlying M. pneumoniae infection and highlights the relevant vaccines that have been developed and their reported effectiveness.

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          The thioredoxin (Trx) system, which is composed of NADPH, thioredoxin reductase (TrxR), and thioredoxin, is a key antioxidant system in defense against oxidative stress through its disulfide reductase activity regulating protein dithiol/disulfide balance. The Trx system provides the electrons to thiol-dependent peroxidases (peroxiredoxins) to remove reactive oxygen and nitrogen species with a fast reaction rate. Trx antioxidant functions are also shown by involvement in DNA and protein repair by reducing ribonucleotide reductase, methionine sulfoxide reductases, and regulating the activity of many redox-sensitive transcription factors. Moreover, Trx systems play critical roles in the immune response, virus infection, and cell death via interaction with thioredoxin-interacting protein. In mammalian cells, the cytosolic and mitochondrial Trx systems, in which TrxRs are high molecular weight selenoenzymes, together with the glutathione-glutaredoxin (Grx) system (NADPH, glutathione reductase, GSH, and Grx) control the cellular redox environment. Recently mammalian thioredoxin and glutathione systems have been found to be able to provide the electrons crossly and to serve as a backup system for each other. In contrast, bacteria TrxRs are low molecular weight enzymes with a structure and reaction mechanism distinct from mammalian TrxR. Many bacterial species possess specific thiol-dependent antioxidant systems, and the significance of the Trx system in the defense against oxidative stress is different. Particularly, the absence of a GSH-Grx system in some pathogenic bacteria such as Helicobacter pylori, Mycobacterium tuberculosis, and Staphylococcus aureus makes the bacterial Trx system essential for survival under oxidative stress. This provides an opportunity to kill these bacteria by targeting the TrxR-Trx system. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults

            Community-acquired pneumonia is a leading infectious cause of hospitalization and death among U.S. adults. Incidence estimates of pneumonia confirmed radiographically and with the use of current laboratory diagnostic tests are needed.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Pathogens
                Pathogens
                pathogens
                Pathogens
                MDPI
                2076-0817
                25 January 2021
                February 2021
                : 10
                : 2
                : 119
                Affiliations
                [1 ]Institution of Pathogenic Biology, Hengyang Medical College, University of South China, Hengyang 421001, China; jiang_zl2020@ 123456126.com (Z.J.); zhourunjie6660@ 123456163.com (R.Z.)
                [2 ]Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong 999077, China; polly.hm.leung@ 123456polyu.edu.hk
                Author notes
                Author information
                https://orcid.org/0000-0003-2406-4773
                Article
                pathogens-10-00119
                10.3390/pathogens10020119
                7911756
                33503845
                962fad4f-3720-4020-9fa6-2382d974856c
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 December 2020
                : 21 January 2021
                Categories
                Review

                mycoplasma pneumonia,virulence factors,pathogenesis,whole-cell vaccine,subunit vaccines,dna vaccines,live vector vaccines

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