Occurrence, Plasticity, and Evolution of the vpma Gene Family, a Genetic System Devoted to High-Frequency Surface Variation in Mycoplasma agalactiae

Abstract

Mycoplasma agalactiae, an important pathogen of small ruminants, exhibits a very versatile surface architecture by switching multiple, related lipoproteins (Vpmas) on and off. In the type strain, PG2, Vpma phase variation is generated by a cluster of six vpma genes that undergo frequent DNA rearrangements via sitespecific recombination. To further comprehend the degree of diversity that can be generated at the M. agalactiae surface, the vpma gene repertoire of a field strain, 5632, was analyzed and shown to contain an extended repertoire of 23 vpma genes distributed between two loci located 250 kbp apart. Loci I and II include 16 and 7 vpma genes, respectively, with all vpma genes of locus II being duplicated at locus I. Several Vpmas displayed a chimeric structure suggestive of homologous recombination, and a global proteomic analysis further indicated that at least 13 of the 16 Vpmas can be expressed by the 5632 strain. Because a single promoter is present in each vpma locus, concomitant Vpma expression can occur in a strain with duplicated loci. Consequently, the number of possible surface combinations is much higher for strain 5632 than for the type strain. Finally, our data suggested that insertion sequences are likely to be involved in 5632 vpma locus duplication at a remote chromosomal position. The role of such mobile genetic elements in chromosomal shuffling of genes encoding major surface components may have important evolutionary and epidemiological consequences for pathogens, such as mycoplasmas, that have a reduced genome and no cell wall.

Critical Role of Dispensable Genes inMycoplasma agalactiaeInteraction with Mammalian Cells

“…Remarkably, whole-genome sequence analysis has revealed that extensive horizontal gene transfer (HGT) events, affecting up to 18% of the M. agalactiae genome, occurred between M. agalactiae and members of the mycoides cluster, illustrating the unexpected plasticity and adaptability of the mycoplasma genome (44,45). Recent advances in whole-genome sequencing have greatly facilitated the study of mycoplasmas (2,33,34,44,45). Unfortunately, these data alone have been of little help in identifying the mechanism underlying diseases caused by mycoplasmas.…”

Unexpected genetic diversity of Mycoplasma agalactiae caprine isolates from an endemic geographically restricted area of Spain

“…In MA, the vpma locus has been thoroughly studied and shown to encode genes with related sequences [15,21-23]. The size of the vpma repertoire (number of vpma genes) varies between strains, but is constant within each strain.…”

Comparative Study of p40 Gene Expression of Mycoplasma Agalactiae Isolated from Iranian Provinces

“…P30, P48, P55 and P80 are surface proteins of Mycoplasma agalactiae, but P40 is the immunodominant protein and suitable for diagnostic assays like ELISA, as a sensitive assay for detection of host serum antibodies against Mycoplasma agalactiae (Nouvel, 2009).…”

“…Many surface lipoproteins including P30, P40, P80, P55, Vpma, P48, etc. which have been found in Mycoplasma agalactiae, are able to switch their gene expression during immune evasion and adherence to epithelium cells underc host physiologic conditions (Nouvel, 2009). Genomic and proteomic analyses have provided powerful immunological insights into a few proteins of this pathogen (including P40, Vpma and P48) as suitable agents for determination kits or detection reports.…”