Bioinformatic analysis of Mycoplasma Pneumoniae virulence factors with a Potential role in human brain invasion

Abstract

This investigation was conducted to identify virulence factors of Mycoplasma pneumoniae from its genome by bioinformatic schemes and to determine their affinities on plasminogen which circulate in blood brain vessel, by molecular modeling. This study shows that enolase is a putative virulence factor. Therefore enolase was then taken to model its three-dimensional structure and to determine the interaction of M. pneumoniae enolase with plasminogen using molecular modeling and molecular docking, respectively. Subsequently the obtained docking model was taken to study in dynamics with implicit water under NVT ensemble to investigate their stabilities. The M. pneumoniae enolase model obtained shows a kidney shape consisted of two domains, the N-terminal domain containing three α helices and three anti-parallel β-sheets, the C-terminal domain forming a (β/α) 8-barrel structure with a small protruding loop. The Mg2+ ion, a metal cofactor is surrounded by D256-E310-D337. Although this model appears to share the same fold of overall structure with those of template and other microbial enolase, it has a particular variant loop of amino acid residue 264 to residue 276. Molecular docking shows the key residues involved in hydrogen bonding which plays an important role in the interaction between M. pneumoniae enolase (e) and human plasminogen (plg) as followed, eR24-plgK48, eK70-plgY50, eN165-plgT66, eA168-plgE21, eD171-plgK70, and eN213-plgP68/plgN69. The interaction result obtained is consistent with experimental data on binding assay that enolase has a binding affinity to plasminogen. This information may propose the prospective of M. pneumoniae invasion across human brain either endothelial cell detachment or endothelial cell remodeling by the facilitating of plasmin, an active form of plasminogen, as well as the pathophysiology of invasion of Escherichia coli and Streptococcus species. Plasmin is activated by tissue plasminogen activator (tPA). Subsequently it would involve in endothelial cell detachment and remodeling by the authorizing of cytokine and chemokine induced by the increase in plasmin. Our result is the first report on molecular interaction, by computational simulation, of M. pneumoniae enolase-plasminogen which provides the structural basis of binding complex that suggests to further experiment and rationale drug design.