Metabolic adaptations underlying evolution of Mycoplasma: Nucleotide metabolism and lipid modulation mechanisms driving growth and membrane fluidity in Mycoplasma bovis.

Pathogenic Mycoplasma is a critical pathogen responsible for plant, animal, and human diseases worldwide. Understanding its genetic characteristics and adaptive evolution is essential for elucidating the related transmission mechanisms and pathogenicity. However, analysing the genetic evolution of Mycoplasma solely at the genome level provides an incomplete understanding of the biological characteristics driven by genetic variation. In this study, Mycoplasma bovis (M. bovis), a pathogen of ruminants, was used as a model organism. A multi-omics approach was employed to perform a comprehensive comparative analysis of the globally prevalent genotype ST52 strain and a novel genotype strain derived from it, which exhibited distinct biological phenotypes. The results demonstrated that the enhanced activity of the nucleotide metabolic pathways in M. bovis support its rapid proliferation during the logarithmic growth phase. Additionally, M. bovis regulates its cell membrane fluidity and enhances its adaptability to osmotic stress through modulation of lysophospholipid content. A novel protein with phospholipase activity, MB0331, was identified and found to enhance membrane fluidity and adaptability to high-glucose environments in M. bovis. MB0331 homologous proteins are widely present in other mycoplasma species. The active nucleotide and lipid metabolic pathways in the novel genotype strain may be correlated with abundant DNA methylation in the gene body. This comprehensive multi-omics analysis advances our understanding of the adaptive evolution of M. bovis and provides new insights and evidence to inform future studies regarding environmental adaptability and genetic variation mechanisms in Mycoplasma.