1.What is VSA and how does it under go size and phase variation?
2.How does VSA variation affect and is effected by the host immune response?
3.How does VSA variation affect growth and nutrition? What are the benefits and liabilities of the different forms of VSA?
4.What are the roles of VSA forms in biofilms formation and how is that hypothisizse to affect the immune response?
1.The mycoplasmas have evolved and adapted to a parasitic mode of life. During this process, they have developed various genetic systems that provide an extremely high plastic set of Variable Surface Proteins (VSP), which is meant to evade the host immune system. In the absence of a cell wall and a periplasmic space, the majority of surface variable antigens in mycoplasmas are lipoproteins. Variable Surface Antigens (Vsa) are the proteins meant to avoid host immune responses, in mycoplasmas and they are present in abundance. They undergo high-frequency phase and size variation. The length of these proteins affects the adherence properties of the mycoplasma as well as its degree of shielding from the immune system. They undergo high-frequency phase and size variation as follows:
Note: View the attachment, MYCOPLASMA VARIABLE SURFACE ANTIGEN[Answers].doc Figure 1A for phase and size variation of the vsa gene.
The vsa locus comprises of a single vsa expression site (depicted by brown color), the promoter (P), various silent vsa genes (depicted by colored arrows) with tandemly repeated sequences, and vsa recombination sites (known as vsr sequences depicted by red arrows). Random inversions occur between vrs sequences, and the vsa expression site recombines with one of the various silent vsa genes (shown as colored arrows). The vsa gene expression region is shown as recombining to a silent gene, which results in the expression of the vsa gene.
Note: View the attachment, MYCOPLASMA VARIABLE SURFACE ANTIGEN[Answers].doc Fig 1B which depicts the mechanism of phase variation in VSA proteins.
The vsa expression site comprises of the conserved 726-bp 5' region of the ORF and the vsa promoter (shown in orange) and ends with a vsa recombination site vrs (shown in red arrows). DNA inversion that is shown through crossed arrows, gets associated with the expression site with a different 3' tandem repeat region, which is a formerly silent vsa gene.
Note: View the attachment, MYCOPLASMA VARIABLE SURFACE ANTIGEN[Answers].doc Fig 1C which depicts mechanism of size variation in VSA proteins.
The variation in size of vsa results from a slipped-strand mispairing, which occurs during DNA replication in the vsa tandem repeat region. This process increases or decreases the number of tandem repeats (shown in orange) in a vsa protein. The variation is size of vsa protein modulates the mycoplasmal cell surface proteins. A short vsaA protein comprising of three tandem repeat units is known as vsaA-R3 (an R3 protein). The long form of a vsa protein is known as R40 as it consists of 40 tandem repeats and at times as many as 60. Similar to phase variation, the size variation occurs at a frequency of 10 -3 per CFU per generation. Variations in size control the mycoplasmal cell surface properties.
2.There is a correlation between the length of the Vsa proteins and the ...
Bacteria with biofilms surrounding them are resistant to antimicrobial agents, due to the reason that, the lower growth rate in biofilms reduces the effectiveness of antibiotics that require high growth rate to kill. Biofilms reduce the diffusion capacity of some antibiotics, such as aminoglycosides. They protect the Vsa forms against antimicrobial peptides. They partially protect M. pulmonis from molecules which form pores in membranes. Cells present in towers within biofilms acquire resistance to complement by producing long Vsa proteins.