Disease relevance of vapA

• The LysR-type transcriptional regulator VirR is required for expression of the virulence gene vapA of Rhodococcus equi ATCC 33701 [1].
• In addition, bacterial clearance and granuloma development in mice is linked to plasmid possession and VapA expression [2].
• VapA-negative Rhodococcus equi in a dog with necrotizing pyogranulomatous hepatitis, osteomyelitis, and myositis [3].
• Delayed type hypersensitivity response and antibody titres in VapA based antigen immunized BALB/c mice were less than in CD1 mice [4].

High impact information on vapA

• Recent sequencing of the virulence plasmid identified a putative pathogenicity island encoding a novel family of seven Vap proteins including VapA [5].
• Isolates of R. equi from pneumonic foals typically contain large, 85- or 90-kb plasmids encoding a highly immunogenic virulence-associated protein (VapA) [6].
• A recombinant, plasmid-cured derivative expressing wild-type levels of VapA failed to replicate in macrophages and remained avirulent for both mice and foals [6].
• However, expression of VapA alone is not sufficient to restore the virulence phenotype [6].
• The transcriptional start site of vapA was determined to be a cytidine located 226 bp upstream from the vapA initiation codon [1].

Chemical compound and disease context of vapA

• An enzyme-linked immunosorbent assay (ELISA) was developed against Rhodococcus equi using Triton X-114 detergent extracted whole cell material, in which the virulence associated protein (VapA) predominated [7].

Biological context of vapA

• No significant sequence homology of the vapA gene with other reported nucleotide sequences were found [8].
• Sequence analysis of this gene (designated vapA) revealed a 570-bp open reading frame encoding a polypeptide of 189 amino acids with a calculated molecular mass of 19,175 Da [8].
• The aim of this study was to determine whether the LysR-type transcriptional regulator VirR, which is encoded by the virulence plasmid, is required for the expression of vapA [1].
• The antibody response of the immunized foals confirmed that VapA and VapC are highly immunogenic [9].
• Detection of R. equi was made by bacteriology and immunohistochemistry for R. equi and VapA, the virulence factor of R. equi [10].

Anatomical context of vapA

• Linear B-cell epitopes of the Rhodococcus equi virulence-associated protein (VapA) were mapped using a synthetic peptide bank in this study [11].
• We developed a DNA vaccine expressing the vapA gene (pVR1055vapA) that induced an anamnestic response characterized by virulence associated protein A (VapA)-specific IgG antibodies in sera and bronchoalveolar lavage fluid (BALF) as well as VapA-specific proliferation of pulmonary lymphocytes when tested in adult ponies [12].
• R. equi and VapA were identified within the lungs of both fetuses, and its distribution correlated with lesions [10].
• 1. The plasmid construct expressed VapA in a COS-7 cell line [13].
• Most strains associated well with HeLa cells and no relationship was found with plasmid status and possession of VapA [14].

Associations of vapA with chemical compounds

• Use of adjuvants (aluminium hydroxide, iscoms) interfered markedly with the immunogenic properties of the VapA based antigen, in the case of aluminium hydroxide by apparently driving a Th2 type of response [4].

Analytical, diagnostic and therapeutic context of vapA

• The expression of VapA, as monitored by Western blotting, was completely dependent on the presence of virR [1].
• Immunization of mice with the lipid-modified VapA purified by SDS-PAGE fractionation or with acetone precipitated VapA protein following TX-114 extraction resulted in significantly enhanced clearance from the liver and spleen following intravenous challenge [8].
• The strains were tested by PCR for the presence of 15- to 17-kDa virulence-associated protein antigen (VapA) and 20-kDa virulence-associated protein antigen (VapB) genes [15].
• B-Cell epitope mapping of the VapA protein of Rhodococcus equi: implications for early detection of R. equi disease in foals [11].
• Restriction enzyme analysis of the virulence plasmids of VapA-positive Rhodococcus equi strains isolated from humans and horses [16].

References