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      Infection strategies of mycoplasmas: Unraveling the panoply of virulence factors

      review-article
      , , , ,
      Virulence
      Taylor & Francis
      Mycoplasmas, adhesins, invasive enzymes, metabolites, toxins

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          ABSTRACT

          Mycoplasmas, the smallest bacteria lacking a cell wall, can cause various diseases in both humans and animals. Mycoplasmas harbor a variety of virulence factors that enable them to overcome numerous barriers of entry into the host; using accessory proteins, mycoplasma adhesins can bind to the receptors or extracellular matrix of the host cell. Although the host immune system can eradicate the invading mycoplasma in most cases, a few sagacious mycoplasmas employ a series of invasion and immune escape strategies to ensure their continued survival within their hosts. For instance, capsular polysaccharides are crucial for anti-phagocytosis and immunomodulation. Invasive enzymes degrade reactive oxygen species, neutrophil extracellular traps, and immunoglobulins. Biofilm formation is important for establishing a persistent infection. During proliferation, successfully surviving mycoplasmas generate numerous metabolites, including hydrogen peroxide, ammonia and hydrogen sulfide; or secrete various exotoxins, such as community-acquired respiratory distress syndrome toxin, and hemolysins; and express various pathogenic enzymes, all of which have potent toxic effects on host cells. Furthermore, some inherent components of mycoplasmas, such as lipids, membrane lipoproteins, and even mycoplasma-generated superantigens, can exert a significant pathogenic impact on the host cells or the immune system. In this review, we describe the proposed virulence factors in the toolkit of notorious mycoplasmas to better understand the pathogenic features of these bacteria, along with their pathogenic mechanisms.

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          Most cited references132

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          Molecular biology and pathogenicity of mycoplasmas.

          The recent sequencing of the entire genomes of Mycoplasma genitalium and M. pneumoniae has attracted considerable attention to the molecular biology of mycoplasmas, the smallest self-replicating organisms. It appears that we are now much closer to the goal of defining, in molecular terms, the entire machinery of a self-replicating cell. Comparative genomics based on comparison of the genomic makeup of mycoplasmal genomes with those of other bacteria, has opened new ways of looking at the evolutionary history of the mycoplasmas. There is now solid genetic support for the hypothesis that mycoplasmas have evolved as a branch of gram-positive bacteria by a process of reductive evolution. During this process, the mycoplasmas lost considerable portions of their ancestors' chromosomes but retained the genes essential for life. Thus, the mycoplasmal genomes carry a high percentage of conserved genes, greatly facilitating gene annotation. The significant genome compaction that occurred in mycoplasmas was made possible by adopting a parasitic mode of life. The supply of nutrients from their hosts apparently enabled mycoplasmas to lose, during evolution, the genes for many assimilative processes. During their evolution and adaptation to a parasitic mode of life, the mycoplasmas have developed various genetic systems providing a highly plastic set of variable surface proteins to evade the host immune system. The uniqueness of the mycoplasmal systems is manifested by the presence of highly mutable modules combined with an ability to expand the antigenic repertoire by generating structural alternatives, all compressed into limited genomic sequences. In the absence of a cell wall and a periplasmic space, the majority of surface variable antigens in mycoplasmas are lipoproteins. Apart from providing specific antimycoplasmal defense, the host immune system is also involved in the development of pathogenic lesions and exacerbation of mycoplasma induced diseases. Mycoplasmas are able to stimulate as well as suppress lymphocytes in a nonspecific, polyclonal manner, both in vitro and in vivo. As well as to affecting various subsets of lymphocytes, mycoplasmas and mycoplasma-derived cell components modulate the activities of monocytes/macrophages and NK cells and trigger the production of a wide variety of up-regulating and down-regulating cytokines and chemokines. Mycoplasma-mediated secretion of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1 (IL-1), and IL-6, by macrophages and of up-regulating cytokines by mitogenically stimulated lymphocytes plays a major role in mycoplasma-induced immune system modulation and inflammatory responses.
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            Interaction of mycoplasmas with host cells.

            The mycoplasmas form a large group of prokaryotic microorganisms with over 190 species distinguished from ordinary bacteria by their small size, minute genome, and total lack of a cell wall. Owing to their limited biosynthetic capabilities, most mycoplasmas are parasites exhibiting strict host and tissue specificities. The aim of this review is to collate present knowledge on the strategies employed by mycoplasmas while interacting with their host eukaryotic cells. Prominant among these strategies is the adherence of mycoplasma to host cells, identifying the mycoplasmal adhesins as well as the mammalian membrane receptors; the invasion of mycoplasmas into host cells including studies on the role of mycoplasmal surface molecules and signaling mechanisms in the invasion; the fusion of mycoplasmas with host cells, a novel process that raises intriguing questions of how microinjection of mycoplasma components into eukaryotic cells subvert and damage the host cells. The observations of diverse interactions of mycoplasmas with cells of the immune system and their immunomodulatory effects and the discovery of genetic systems that enable mycoplasmas to rapidly change their surface antigenic composition have been important developments in mycoplasma research over the past decade, showing that mycoplasmas possess an impressive capability of maintaining a dynamic surface architecture that is antigenically and functionally versatile, contributing to the capability of the mycoplasmas to adapt to a large range of habitats and cause diseases that are often chronic in nature.
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              Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae.

              The entire genome of the bacterium Mycoplasma pneumoniae M129 has been sequenced. It has a size of 816,394 base pairs with an average G+C content of 40.0 mol%. We predict 677 open reading frames (ORFs) and 39 genes coding for various RNA species. Of the predicted ORFs, 75.9% showed significant similarity to genes/proteins of other organisms while only 9.9% did not reveal any significant similarity to gene sequences in databases. This permitted us tentatively to assign a functional classification to a large number of ORFs and to deduce the biochemical and physiological properties of this bacterium. The reduction of the genome size of M. pneumoniae during its reductive evolution from ancestral bacteria can be explained by the loss of complete anabolic (e.g. no amino acid synthesis) and metabolic pathways. Therefore, M. pneumoniae depends in nature on an obligate parasitic lifestyle which requires the provision of exogenous essential metabolites. All the major classes of cellular processes and metabolic pathways are briefly described. For a number of activities/functions present in M. pneumoniae according to experimental evidence, the corresponding genes could not be identified by similarity search. For instance we failed to identify genes/proteins involved in motility, chemotaxis and management of oxidative stress.
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                Author and article information

                Journal
                Virulence
                Virulence
                Virulence
                Taylor & Francis
                2150-5594
                2150-5608
                11 March 2021
                2021
                11 March 2021
                : 12
                : 1
                : 788-817
                Affiliations
                [0001]Institute of Pathogenic Biology, Hengyang Medical College, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study; , Hengyang, China
                Author notes
                CONTACT You Xiaoxing youxiaoxing@ 123456usc.edu.cn
                Author information
                https://orcid.org/0000-0002-8897-3186
                Article
                1889813
                10.1080/21505594.2021.1889813
                7954426
                33704021
                1fe7dd36-f9d2-44b7-bd44-a74911fdd727
                © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 1, Tables: 2, References: 305, Pages: 30
                Categories
                Review Article
                Review Article

                Infectious disease & Microbiology
                mycoplasmas,adhesins,invasive enzymes,metabolites,toxins
                Infectious disease & Microbiology
                mycoplasmas, adhesins, invasive enzymes, metabolites, toxins

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