Free exopolysaccharide from Mycoplasma mycoides subsp. mycoides possesses anti-inflammatory properties

Totté, Philippe; Puech, Carinne; Rodrigues, Valérie; Bertin, Clothilde; Manso-Silván, Lucía; Thiaucourt, François

doi:10.1186/s13567-015-0252-6

Cited by 22 publications

(23 citation statements)

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“…Galactan was shown to protect M. mycoides subsp. mycoides from serum killing when cell attached (15) and to possess anti-inflammatory properties when secreted as an exopolysaccharide (14). We have demonstrated here that M. agalactiae strains producing ␤-(1¡6)-glucan in contact with goat sera or the complement fraction of guinea pig sera were rapidly killed, suggesting that they might be rapidly eliminated from the bloodstream of infected animals, prior to the acquisition of antimycoplasma immunity.…”

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confidence: 79%

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Mycoplasma agalactiae Secretion of β-(1→6)-Glucan, a Rare Polysaccharide in Prokaryotes, Is Governed by High-Frequency Phase Variation

Gaurivaud

Baranowski

Pau-Roblot

et al. 2016

Appl Environ Microbiol

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Mycoplasmas are minimal, wall-less bacteria but have retained the ability to secrete complex carbohydrate polymers that constitute a glycocalyx. In members of the Mycoplasma mycoides cluster, which are important ruminant pathogens, the glycocalyx includes both cell-attached and cell-free polysaccharides. This report explores the potential secretion of polysaccharides by M. agalactiae, another ruminant pathogen that belongs to a distant phylogenetic group. Comparative genomic analyses showed that M. agalactiae possesses all the genes required for polysaccharide secretion. Notably, a putative synthase gene (gsmA) was identified, by in silico reconstruction of the biosynthetic pathway, that could be involved in both polymerization and export of the carbohydrate polymers. M. agalactiae polysaccharides were then purified in vitro and found to be mainly cell attached, with a linear ␤-(1¡6)-glucopyranose structure [␤-(1¡6)-glucan]. Secretion of ␤-(1¡6)-glucan was further shown to rely on the presence of a functional gsmA gene, whose expression is subjected to high-frequency phase variation. This event is governed by the spontaneous intraclonal variation in length of a poly(G) tract located in the gsmA coding sequence and was shown to occur in most of the M. agalactiae clinical isolates tested in this study. M. agalactiae susceptibility to serum-killing activity appeared to be dictated by ON/OFF switching of ␤-(1¡6)-glucan secretion, suggesting a role of this phenomenon in survival of the pathogen when it invades the host bloodstream. Finally, ␤-(1¡6)-glucan secretion was not restricted to M. agalactiae but was detected also in M. mycoides subsp. capri PG3 T , another pathogen of small ruminants. IMPORTANCEMany if not all bacteria are able to secrete polysaccharides, either attached to the cell surface or exported unbound into the extracellular environment. Both types of polysaccharides can play a role in bacterium-host interactions. Mycoplasmas are no exception despite their poor overall metabolic capacity. We showed here that M. agalactiae secretes a capsular ␤-(1¡6)-glucopyranose thanks to a specific glycosyltransferase with synthase activity. This secretion is governed by high-frequency ON/OFF phase variation that might be crucial in mycoplasma host dissemination, as cell-attached ␤-(1¡6)-glucopyranose increases serum-killing susceptibility. Our results provide functional genetic data about mycoplasmal glycosyltransferases with dual functions, i.e., assembly and export of the sugar polymers across the cell membrane. Furthermore, we demonstrated that nonprotein epitopes can be subjected to surface antigenic variation in mycoplasmas. Finally, the present report contributes to unravel the role of secreted polysaccharides in the virulence and pathogenicity of these peculiar bacteria.

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confidence: 79%

“…The role of ␤-(1¡2)-glucan has not yet been studied, but the galactan in M. mycoides subsp. mycoides strain Afadé has been found both to exhibit anti-inflammatory properties in EPS form (14) and to protect the cells from the bactericidal activity of the serum when in CPS form (15).…”

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confidence: 99%

Mycoplasma agalactiae Secretion of β-(1→6)-Glucan, a Rare Polysaccharide in Prokaryotes, Is Governed by High-Frequency Phase Variation

Gaurivaud

Baranowski

Pau-Roblot

et al. 2016

Appl Environ Microbiol

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“…Despite lacking a cell wall, some mycoplasma can produce capsular polysaccharides and/or exopolysaccharides (Neyrolles et al, 1998; Daubenspeck et al, 2009; Bertin et al, 2013, 2015; Simmons et al, 2013; Gaurivaud et al, 2016). Among these identified polysaccharides, some carbohydrate components have been characterized to have anti-inflammatory effects and contribute to biofilms formation (Totté et al, 2015). At the moment, few studies have been carried out regarding capsular polysaccharides and/or exopolysaccharides or their influence on the host during the process of mycoplasma infection, such as their participation in cell adhesion or anti-phagocytosis effects.…”

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confidence: 99%

Subversion of the Immune Response by Human Pathogenic Mycoplasmas

2019

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Mycoplasmas are a large group of prokaryotes which is believed to be originated from Gram-positive bacteria via degenerative evolution, and mainly capable of causing a wide range of human and animal infections. Although innate immunity and adaptive immunity play crucial roles in preventing mycoplasma infection, immune response that develops after infection fails to completely eliminate this bacterium under certain circumstances. Thus, it is reasonable to speculate that mycoplasmas employ some mechanisms to deal with coercion of host defense system. In this review, we will highlight and provide a comprehensive overview of immune evasion strategies that have emerged in mycoplasma infection, which can be divided into four aspects: (i) Molecular mimicry and antigenic variation on the surface of the bacteria to evade the immune surveillance; (ii) Overcoming the immune effector molecules assaults: Induction of detoxified enzymes to degradation of reactive oxygen species; Expression of nucleases to degrade the neutrophil extracellular traps to avoid killing by Neutrophil; Capture and cleavage of immunoglobulins to evade humoral immune response; (iii) Persistent survival: Invading into the host cell to escape the immune damage; Formation of a biofilm to establish a persistent infection; (iv) Modulation of the immune system to down-regulate the intensity of immune response. All of these features increase the probability of mycoplasma survival in the host and lead to a persistent, chronic infections. A profound understanding on the mycoplasma to subvert the immune system will help us to better understand why mycoplasma is so difficult to eradicate and ultimately provide new insights on the development of therapeutic regimens against this bacterium in future.

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“…Based on in vitro experiments, it has been suggested that the Mycoplasma gallisepticum capsule is involved in adhesion and virulence [2], the exopolysaccharides of Mycoplasma pulmonis protect against the complement system [3], CPS of Mycoplasma dispar down-regulates macrophage function [4], and purified CPS of Mycoplasma ovipneumoniae induces an inflammatory response through Toll-like receptor signaling in airway epithelial cells [5]. The exopolysaccharides of members of the “ Mycoplasma mycoides cluster” have been characterized [6] and free CPS of M. mycoides induces the production of interleukin 10 in bovine macrophages, which acts as an anti-inflammatory [7].…”

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confidence: 99%