Molecular mechanisms of gene expression regulation in Mycoplasma spp.: insights into virulence-related genes

Mycoplasma spp. are genome-reduced bacteria, many of which are pathogenic for humans and livestock. The mechanisms driving host colonization and pathogenicity for mycoplasmas remain only partially understood. These processes are influenced by both genomic factors, such as variations in gene content and organization, and regulatory mechanisms that control the expression of virulence-related genes. This review provides a comprehensive survey of the molecular mechanisms governing gene expression regulation in mycoplasmas, with particular interest on virulence-related genes. Mycoplasmas have undergone reductive and convergent evolutionary processes, which have shaped the distribution of virulence-related genes and the variability in their regulatory sequences, leading to species-specific pathogenic strategies. At the transcriptional level, only a small fraction of genes is regulated by transcription factor binding, suggesting that mycoplasmas rely on alternative regulatory mechanisms, such as supercoiling and chromosome topology. Additionally, gene expression in mycoplasma is regulated at the post-transcriptional level, as evidenced by comparative transcriptomics and proteomics studies. Despite recent advances, significant gaps remain in understanding the specific mechanisms of virulence gene regulation, particularly at the post-transcriptional level. This review highlights the need for further research into the complex interplay between genomic organization and regulatory mechanisms underlying mycoplasma pathogenicity, providing a foundation for future studies.