Genomic characterization and pathogenicity validation of Mycoplasma ovipneumoniae strains from diseased sheep: insights into potential pathogenic mechanisms of GSWW364
摘要
Mycoplasma ovipneumoniae (Mo) is the primary etiological agent of mycoplasmal pneumonia of sheep in China, posing a significant threat to the sheep industry. In this study, 18 strains of Mo were isolated from nasal swab samples collected from diseased Hu sheep at nine farms in Gansu Province. Nine representative strains were selected for whole-genome sequencing (WGS) and analysis to explore the genetic relationships between the isolates and reference strains from different regions and hosts. On the basis of the cultural characteristics and the genetic variability among regional strains, strain GSWW364 was chosen for further experiments. A total of 100 healthy 2-month-old Hu sheep were challenged experimentally with strain GSWW364 at a dose of 1 × 107 color change units (CCU). Fifty-four sheep exhibited typical clinical symptoms, including elevated body temperature, coughing, and pulmonary lesions, confirming the pathogenicity of GSWW364. Transcriptomic analyses at both the tissue and cellular levels revealed three infection-associated differentially expressed genes (DEGs): HIF1A, SLC2A3, and SLC38A1. Validation confirmed significantly upregulated expression of these genes in diseased lung tissues. Knockdown of these genes in sheep alveolar epithelial type II cells significantly reduced Mo adhesion. These findings suggest that these genes may promote pathogen adhesion and inflammatory responses by regulating hypoxia-responsive and metabolic pathways during infection. Collectively, this study provides a scientific basis for the prevention and control of mycoplasmal pneumonia of sheep and lays the groundwork for further investigation into the disease’s pathological mechanisms. It also offers valuable insights for vaccine development and disease-resistant breeding programs.
Graphical Abstract