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Background  The respiratory tract of swine is colonized by several bacteria among which are three  Mycoplasma  species:  Mycoplasma flocculare ,  Mycoplasma hyopneumoniae  and  Mycoplasma hyorhinis . While colonization by  M. flocculare  is virtually asymptomatic,  M. hyopneumoniae  is the causative agent of enzootic pneumonia and  M. hyorhinis  is present in cases of pneumonia, polyserositis and arthritis. The genomic resemblance among these three  Mycoplasma  species combined with their different levels of pathogenicity is an indication that they have unknown mechanisms of virulence and differential expression, as for most mycoplasmas.    Methods  In this work, we performed whole-genome metabolic network reconstructions for these three mycoplasmas. Cultivation tests and metabolomic experiments through nuclear magnetic resonance spectroscopy (NMR) were also performed to acquire experimental data and further refine the models reconstructed  in silico .    Results  Even though the refined models have similar metabolic capabilities, interesting differences include a wider range of carbohydrate uptake in  M. hyorhinis , which in turn may also explain why this species is a widely contaminant in cell cultures. In addition, the myo-inositol catabolism is exclusive to  M. hyopneumoniae  and may be an important trait for virulence. However, the most important difference seems to be related to glycerol conversion to dihydroxyacetone-phosphate, which produces toxic hydrogen peroxide. This activity, missing only in  M. flocculare , may be directly involved in cytotoxicity, as already described for two lung pathogenic mycoplasmas, namely  Mycoplasma pneumoniae  in human and  Mycoplasma mycoides  subsp.  mycoides  in ruminants. Metabolomic data suggest that even though these mycoplasmas are extremely similar in terms of genome and metabolism, distinct products and reaction rates may be the result of differential expression throughout the species.    Conclusions  We were able to infer from the reconstructed networks that the lack of pathogenicity of  M. flocculare  if compared to the highly pathogenic  M. hyopneumoniae  may be related to its incapacity to produce cytotoxic hydrogen peroxide. Moreover, the ability of  M. hyorhinis  to grow in diverse sites and even in different hosts may be a reflection of its enhanced and wider carbohydrate uptake. Altogether, the metabolic differences highlighted  in silico  and in vitro provide important insights to the different levels of pathogenicity observed in each of the studied species.    Electronic supplementary material  The online version of this article (doi:10.1186/s12864-016-2644-z) contains supplementary material, which is available to authorized users.

Insights on the virulence of swine respiratory tract mycoplasmas through genome-scale metabolic modeling