Featured Species-Specific Loops Are Found in the Crystal Structure of Mhp Eno, a Cell Surface Adhesin From Mycoplasma hyopneumoniae

Abstract

Enolase is an evolutionarily conserved enzyme involved in the processes of glycolysis and gluconeogenesis. Mycoplasma hyopneumoniae belongs to Mycoplasma , whose species are wall-less and among the smallest self-replicating bacteria, and is an important colonizing respiratory pathogen in the pig industry worldwide. Mycoplasma hyopneumoniae enolase ( Mhp Eno) expression is significantly increased after infection and was previously found to be a virulence factor candidate. Our studies show that Mhp Eno is a cell surface-localized protein that can adhere to swine tracheal epithelial cells (STECs). Adhesion to STECs can be specifically inhibited by an Mhp Eno antibody. Mhp Eno can recognize and interact with plasminogen with high affinity. Here, the first crystal structure of the mycoplasmal enolase from Mycoplasma hyopneumoniae was determined. The structure showed unique features of Mhp Eno in the S3/H1, H6/S6, H7/H8, and H13 regions. All of these regions were longer than those of other enolases and were exposed on the Mhp Eno surface, making them accessible to host molecules. These results show that Mhp Eno has specific structural characteristics and acts as a multifunctional adhesin on the Mycoplasma hyopneumoniae cell surface.

Mycoplasma hyorhinis as a possible cause of fibrinopurulent meningitis in pigs? - a case series

“…For example, in S. suis serotype 2 enolase was suggested to be a potential virulence factor for CNS invasion as it induced IL-8 release [23]. Although enolase, an enzyme of the glycolytic pathway and prototypic moonlighting protein, has shown to act as adhesin on the cell surface of several mycoplasma species [26][27][28][29][30], its potential moonlighting activity in Mhr remains to be elucidated. Interestingly, enolase is also suggested to play a role in human tic disorders and to act as an autoantigen in Hashimoto's encephalopathy [31,32].…”

Pathogenicity & virulence ofMycoplasma hyopneumoniae

“…The insoluble secretome (or surfaceome) of M. hyopneumoniae also acts as a reservoir of virulence factors (Table 2), which strongly contribute to EP establishment. Proteomic studies focused on surface proteins have demonstrated that this cell fraction is enriched with adhesion proteins (discussed in section 4.1), lipoproteins, and proteases, among others [75,86]. The roles of these proteins in immunomodulation and cell damage are discussed in the following sections.…”

“…A repertoire of at least 35 M. hyopneumoniae proteins have been previously associated with cell adhesion, including several related to the P97/P102 paralog families and other surface proteins that moonlight as adhesins [78,84,85] (Table 1). However, the number of M. hyopneumoniae adhesins can be higher, considering that its surfaceome includes more than 290 proteins [72,75,86] and that many uncharacterized surfacedisplayed proteins may bear adhesion properties. Moreover, M. hyopneumoniae pathogenic and nonpathogenic strains, and the nonpathogenic M. flocculare, which differ in pathogenicity and were classically described as having differential adhesion capacities [87], share almost their entire repertoires of known adhesins, according to more recent comparative genomics and proteomics studies [72,75,87], also pointing out to differences beyond the mere sets of known adhesins.…”

Infection strategies of mycoplasmas: Unraveling the panoply of virulence factors

“…Moreover, both MHJ_0125, a glutamyl aminopeptidase, and MHJ_0461, a leucine aminopeptidase, have moonlighting roles as adhesins on the surface of M. hyopneumoniae; MHJ_0461 also binds to foreign double-stranded DNA [51,52]. Eno in M. hyopneumoniae and M. suis also play crucial roles in adherence, invasion, and infections [53,54].…”