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Surface diversity in Mycoplasma agalactiae is driven by site-specific DNA inversions within the vpma multigene locus
Michelle D Glew1, Marc Marenda, Renate Rosengarten
1Institute of Bacteriology, Mycology and Hygiene, University of Veterinary Medicine, 1210 Vienna, Austria.
Abstract:
The ruminant pathogen Mycoplasma agalactiae possesses a family of abundantly expressed variable surface lipoproteins called Vpmas. Phenotypic switches between Vpma members have previously been correlated with DNA rearrangements within a locus of vpma genes and are proposed to play an important role in disease pathogenesis. In this study, six vpma genes were characterized in the M. agalactiae type strain PG2. All vpma genes clustered within an 8-kb region and shared highly conserved 5' untranslated regions, lipoprotein signal sequences, and short N-terminal sequences. Analyses of the vpma loci from consecutive clonal isolates showed that vpma DNA rearrangements were site specific and that cleavage and strand exchange occurred within a minimal region of 21 bp located within the 5' untranslated region of all vpma genes. This process controlled expression of vpma genes by effectively linking the open reading frame (ORF) of a silent gene to a unique active promoter sequence within the locus. An ORF (xer1) immediately adjacent to one end of the vpma locus did not undergo rearrangement and had significant homology to a distinct subset of genes belonging to the lambda integrase family of site-specific xer recombinases. It is proposed that xer1 codes for a site-specific recombinase that is not involved in chromosome dimer resolution but rather is responsible for the observed vpma-specific recombination in M. agalactiae.
Insights
Mycoplasma agalactiae switches variable surface Vpma proteins through site-specific DNA recombination. This process, controlled by the xer1 recombinase, allows the pathogen to evade host immunity during infection.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Mycoplasma agalactiae causes disease in ruminants.
- Variable surface lipoproteins (Vpmas) are key virulence factors.
- Vpma switching is linked to DNA rearrangements and pathogenesis.
Purpose of the Study:
- To characterize the vpma gene locus in M. agalactiae.
- To investigate the mechanism of vpma DNA rearrangements.
- To identify the genetic factors responsible for vpma switching.
Main Methods:
- Characterization of six vpma genes in M. agalactiae PG2.
- Analysis of vpma loci from consecutive clonal isolates.
- Homology searches for genes adjacent to the vpma locus.
Main Results:
- All vpma genes are clustered and share conserved regions.
- DNA rearrangements are site-specific, occurring within a 21 bp region.
- A gene, xer1, homologous to lambda integrase family recombinases, is adjacent to the vpma locus.
Conclusions:
- A site-specific recombination mechanism controls vpma gene expression.
- The xer1 gene likely encodes a recombinase responsible for vpma switching.
- This switching mechanism is crucial for M. agalactiae pathogenesis.