Hydrogen peroxide production and myo‐inositol metabolism as important traits for virulence ofMycoplasma hyopneumoniae

Abstract

Mycoplasma hyopneumoniae is the causative agent of enzootic pneumonia. In our previous work, we reconstructed the metabolic models of this species along with two other mycoplasmas from the respiratory tract of swine: Mycoplasma hyorhinis, considered less pathogenic but which nonetheless causes disease and Mycoplasma flocculare, a commensal bacterium. We identified metabolic differences that partially explained their different levels of pathogenicity. One important trait was the production of hydrogen peroxide from the glycerol metabolism only in the pathogenic species. Another important feature was a pathway for the metabolism of myo-inositol in M. hyopneumoniae. Here, we tested these traits to understand their relation to the different levels of pathogenicity, comparing not only the species but also pathogenic and attenuated strains of M. hyopneumoniae. Regarding the myo-inositol metabolism, we show that only M. hyopneumoniae assimilated this carbohydrate and remained viable when myo-inositol was the primary energy source. Strikingly, only the two pathogenic strains of M. hyopneumoniae produced hydrogen peroxide in complex medium. We also show that this production was dependent on the presence of glycerol. Although further functional tests are needed, we present in this work two interesting metabolic traits of M. hyopneumoniae that might be directly related to its enhanced virulence. Abbreviated SummaryVirulence and pathogenicity of Mycoplasma hyopneumoniae, the causative agent of enzootic pneumonia, has never been fully understood. We present in this work two interesting metabolic traits of M. hyopneumoniae that might be directly related to its enhanced virulence, especially regarding its ability to produce hydrogen peroxide. IntroductionThe notion that the lungs are sterile is frequently stated in textbooks; however, no modern studies have provided evidence for the absence of microorganisms in this environment [1]. Several bacteria colonize the respiratory tract of swine.Mycoplasma hyopneumoniae, Mycoplasma flocculare, and Mycoplasma hyorhinis are some of the most important species identified so far [2,3,4,5].M. hyopneumoniae is widespread in pig populations and is the causative agent of enzootic pneumonia [6]; M. hyorhinis, although not as pathogenic as M.hyopneumoniae, has already been found as the sole causative agent of pneumonia, polyserositis and arthritis in pigs [7,8,9,10]. M. flocculare, on the other hand, has high prevalence in swine herds worldwide, but up to now, is still considered a commensal bacterium [7].Because of the genomic resemblance of these three Mycoplasma species [11,12], it remains unclear why M. hyopneumoniae can become highly virulent if compared with the other two. It is also essential to understand that the simple presence or absence of each species is not in itself a determinant factor in the development of enzootic pneumonia: most piglets are thought to be vertically infected with M. hyopneumoniae at birth [6,13,14] and many can become carriers of the pathogen throughout their...

Comparative proteomics of twoMycoplasma hyopneumoniaestrains andMycoplasma flocculareidentified potential porcine enzootic pneumonia determinants

“…mycoides [28,29]. In line with that, it was recently demonstrated that pathogenic strains of M. hyopneumoniae were able to produce hydrogen peroxide from glycerol metabolism, but that the non-pathogenic strain J and M. flocculare were not [11]. M. hyopneumoniae uptakes and metabolizes glycerol, while M. flocculare does not, failing to produce cytotoxic levels of hydrogen peroxide, which can be explained by the absence, in the M. flocculare genome, of the glpO gene, related to glycerol metabolism and hydrogen peroxide production [12].…”

“…Moreover, previous comparative phylogenetic and phylogenomic studies provided evidences of the close relationship of M. hyopneumoniae and M. flocculare [7–9], which share most of the known virulence-related genes [10]. The differences between M. hyopneumoniae and M. flocculare include the absence, in M. flocculare , of the glpO gene, related to M. hyopneumoniae hydrogen peroxide generation and cytotoxicity [11,12], and differential domains between orthologs from the P97 family of adhesins and from other surface proteins [13]. However, 90% of M. flocculare predicted surface proteins are shared with M. hyopneumoniae [9], and the observed genomic differences between M. hyopneumoniae strains, and between M. hyopneumoniae and M. flocculare so far do not fully explain their differential phenotypes of virulence/pathogenicity.…”

Mycoplasma hyopneumoniae J elicits an antioxidant response and decreases the expression of ciliary genes in infected swine epithelial cells

“…mycoides was correlated to the bacterium's ability to translocate hydrogen peroxide directly into the host cell 36 . Previously, we have identified that M. hyopneumoniae was capable of producing this toxic product from glycerol metabolism 5 . Although the production of hydrogen peroxide by the M. hyopneumoniae strain J was not detected in that work, novel analyses indicate that in conditions where glucose is scarce, the attenuated strain J is able to produce this toxic metabolite ( Supplementary Fig.…”

Mycoplasma hyopneumoniaevariability:Current trends and proposed terminology for genomic classification

“…Therefore, the ability to detect the presence of unidentified toxins for other Mycoplasma species may be possible in the future. Ferrarini et al () recently demonstrated that pathogenic strains of M. hyopneumoniae are able to use glycerol as a carbon source thereby enabling the production of the toxic metabolite hydrogen peroxide. In a previous study, Ferrarini et al () showed that only M. hyopneumoniae, but not the commensal M. flocculare, was able to assimilate myo‐inositol and remained viable when this was the primary energy source.…”