Identification of a VapA virulence factor functional homolog in Rhodococcus equi isolates housing the pVAPB plasmid.
Abstract: Rhodococcus equi is a facultative intracellular bacterium of macrophages and is an important pathogen of animals and immunocompromised people wherein disease results in abcessation of the lungs and other sites. Prior work has shown that the presence of the major virulence determinant, VapA, encoded on the pVAPA-type plasmid, disrupts normal phagosome development and is essential for bacterial replication within macrophages. pVAPA- type plasmids are typical of R. equi strains derived from foals while strains from pigs carry plasmids of the pVAPB-type, lacking vapA, and those from humans harbor various types of plasmids including pVAPA and pVAPB. Through the creation and analysis of a series of gene deletion mutants, we found that vapK1 or vapK2 is required for optimal intracellular replication of an R. equi isolate carrying a pVAPB plasmid type. Complementation analysis of a ΔvapA R. equi strain with vapK1 or vapK2 showed the VapK proteins of the pVAPB-type plasmid could restore replication capacity to the macrophage growth-attenuated ΔvapA strain. Additionally, in contrast to the intracellular growth capabilities displayed by an equine R. equi transconjugant strain carrying a pVAPB-type plasmid, a transconjugant strain carrying a pVAPB-type plasmid deleted of vapK1 and vapK2 proved incapable of replication in equine macrophages. Cumulatively, these data indicate that VapK1 and K2 are functionally equivalent to VapA.
Publication Date: 2018-10-04 PubMed ID: 30286098PubMed Central: PMC6171844DOI: 10.1371/journal.pone.0204475Google Scholar: Lookup
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- Journal Article
Summary
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The research article focuses on the bacterium Rhodococcus equi, a pathogen in animals and immunocompromised individuals causing lung abscesses, and the role of a key viral factor, VapA. This study discovered an equivalent viral factor, VapK1 and VapK2, in versions of R. equi that affect pigs and humans, suggesting functional homology.
Introduction and Background Information
- Rhodococcus equi is a bacterium that primarily affects macrophages (immune cells) in animals and people with weak immune systems.
- For this bacterium to effectively grow and replicate within hosts, it relies on a chief virulence, or severity factor, known as VapA, which is found on a specific type of plasmid (genetic material) known as pVAPA.
- R. equi strains differ in animals and humans, with porcine (pig) strains carrying the pVAPB-type plasmid and human strains housing various types of plasmids, including pVAPA and pVAPB. The pVAPB plasmid does not contain the vapA gene.
Research Process and Findings
- The researchers constructed and analyzed a series of gene deletion mutants in order to identify key genes required for optimal replication of R. equi with a pVAPB plasmid.
- It was found that the genes vapK1 or vapK2 were necessary to the process. When either of these genes were added to an R.equi strain without VapA, replication capacity was restored, suggesting they were functionally equivalent to VapA.
- Furthermore, it was observed that an R. equi strain that can typically grow within cells, when carrying a pVAPB-type plasmid, was unable to replicate in horse macrophages when vapK1 and vapK2 were removed.
Conclusion
- The research concluded that VapK1 and VapK2 functioned in a manner similar to VapA. This discovery suggests that VapK1 and VapK2 might be critical virulence factor in R. equi infections in pigs and humans.
- Understanding the role of these key virulence factors could potentially help in developing better treatments or preventive measures against R. equi infections.
Cite This Article
APA
Willingham-Lane JM, Coulson GB, Hondalus MK.
(2018).
Identification of a VapA virulence factor functional homolog in Rhodococcus equi isolates housing the pVAPB plasmid.
PLoS One, 13(10), e0204475.
https://doi.org/10.1371/journal.pone.0204475 Publication
Researcher Affiliations
- Department of Infectious Disease, University of Georgia, Athens, Georgia, United States of America.
- Department of Infectious Disease, University of Georgia, Athens, Georgia, United States of America.
- Department of Infectious Disease, University of Georgia, Athens, Georgia, United States of America.
MeSH Terms
- Actinomycetales Infections / microbiology
- Actinomycetales Infections / veterinary
- Animals
- Bacterial Proteins / genetics
- Cells, Cultured
- Female
- Horse Diseases / microbiology
- Horses
- Macrophages / microbiology
- Mice, Inbred BALB C
- Mutation
- Plasmids
- Rhodococcus equi / genetics
- Rhodococcus equi / growth & development
- Rhodococcus equi / isolation & purification
- Rhodococcus equi / pathogenicity
- Virulence Factors / genetics
Conflict of Interest Statement
The authors have declared that no competing interests exist.
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Citations
This article has been cited 6 times.- Hansen P, Haubenthal T, Reiter C, Kniewel J, Bosse-Plois K, Niemann HH, von Bargen K, Haas A. Differential Effects of Rhodococcus equi Virulence-Associated Proteins on Macrophages and Artificial Lipid Membranes. Microbiol Spectr 2023 Feb 14;11(2):e0341722.
- Ivshina IB, Kuyukina MS, Krivoruchko AV, Tyumina EA. Responses to Ecopollutants and Pathogenization Risks of Saprotrophic Rhodococcus Species. Pathogens 2021 Aug 2;10(8).
- Geerds C, Haas A, Niemann HH. Conformational changes of loops highlight a potential binding site in Rhodococcus equi VapB. Acta Crystallogr F Struct Biol Commun 2021 Aug 1;77(Pt 8):246-253.
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- Yerlikaya Z, Miranda-CasoLuengo R, Yin Y, Cheng C, Meijer WG. Clade-1 Vap virulence proteins of Rhodococcus equi are associated with the cell surface and support intracellular growth in macrophages. PLoS One 2025;20(1):e0316541.
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