Comparative genomic analysis of Mycoplasma agalactiae strain GM139 highlights unique surface architecture and pathogenic determinants

Mycoplasma agalactiae causes one of the most serious forms of mycoplasmosis in small ruminants that is notifiable to the World Organization for Animal Health (WOAH). Possessing a plastic genome, its Vpma and other surface antigenic variations play important roles in its pathogenesis and systemic spread within the goat or sheep host, as well as its ability to jump to wild animals. The Vpma phenotypic profile of strain GM139 was recently compared to that of the type strain PG2, whereby GM139 predominantly exhibited stable expression of a single VpmaV protein in comparison with the high-frequency variable expression of all six Vpma proteins in PG2. The complete genome sequence of GM139 was generated, annotated for detailed analysis of the vpma locus and compared with the finished genomes of three distinct M. agalactiae strains (PG2, 5632, and GrTh01). Interestingly, GM139 presented a longer distinct vpma locus with ten genes, one of which is a chimera between the vpmaV and vpmaZ genes of PG2, which correlates very well with previous immunoblotting results and was confirmed here by nanoLC-MS/MS analysis; five vpmas are completely unique, whereas the other four share similarities with the vpmas of 5632, one of which is also partially homologous to vpmaZPG2. Additionally, features such as a larger spma locus, an intact gsmA known to encode a phase-variable glucan affecting serum resistance, and the presence of integrative and conjugative element (ICE) and transposases might have also influenced the pathogenicity and host range of these strains, segregating them into two well-separated phylogenetic clusters on the basis of a newly developed cgMLST scheme. This study highlights the plasticity and dynamic evolution of the M. agalactiae genome, especially its surface antigenic architecture. Mycoplasma agalactiae causes one of the most serious forms of mycoplasmosis in small ruminants that is notifiable to the World Organization for Animal Health (WOAH). Possessing a plastic genome, its Vpma and other surface antigenic variations play important roles in its pathogenesis and systemic spread within the goat or sheep host, as well as its ability to jump to wild animals. The Vpma phenotypic profile of strain GM139 was recently compared to that of the type strain PG2, whereby GM139 predominantly exhibited stable expression of a single VpmaV protein in comparison with the high-frequency variable expression of all six Vpma proteins in PG2. The complete genome sequence of GM139 was generated, annotated for detailed analysis of the vpma locus and compared with the finished genomes of three distinct M. agalactiae strains (PG2, 5632, and GrTh01). Interestingly, GM139 presented a longer distinct vpma locus with ten genes, one of which is a chimera between the vpmaV and vpmaZ genes of PG2, which correlates very well with previous immunoblotting results and was confirmed here by nanoLC-MS/MS analysis; five vpmas are completely unique, whereas the other four share similarities with the vpmas of 5632, one of which is also partially homologous to vpmaZPG2. Additionally, features such as a larger spma locus, an intact gsmA known to encode a phase-variable glucan affecting serum resistance, and the presence of integrative and conjugative element (ICE) and transposases might have also influenced the pathogenicity and host range of these strains, segregating them into two well-separated phylogenetic clusters on the basis of a newly developed cgMLST scheme. This study highlights the plasticity and dynamic evolution of the M. agalactiae genome, especially its surface antigenic architecture.© 2025. The Author(s).

• VetImaging

Universidade Federal da Bahia