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Mouse lung infection model to assess Rhodococcus equi virulence and vaccine protection.
Abstract: The pathogenic actinomycete Rhodococcus equi causes severe purulent lung infections in foals and immunocompromised people. Although relatively unsusceptible to R. equi, mice are widely used for in vivo studies with this pathogen. The most commonly employed mouse model is based on systemic (intravenous) infection and determination of R. equi burdens in spleen and liver. Here, we investigated the murine lung for experimental infection studies with R. equi. Using a 10(7)CFU intranasal challenge in BALB/c mice, virulent R. equi consistently survived in quantifiable numbers up to 10 days in the lungs whereas virulence-deficient R. equi bacteria were rapidly cleared. An internally controlled virulence assay was developed in which the test R. equi strains are co-inoculated and monitored in the same mouse. Isogenic R. equi bacteria lacking either the plasmid vapA gene or the entire virulence plasmid were compared using this competitive assay. Both strains showed no significant differences in in vivo fitness in the lung, indicating that the single loss of the virulence factor VapA was sufficient to account for the full attenuation seen in the absence of the virulence plasmid. To test the adequacy of the lung infection model for monitoring R. equi vaccine efficacy, BALB/c mice were immunized with live R. equi and challenged intranasally. Vaccination conferred protection against acute pulmonary challenge with virulent R. equi. Our data indicate that the murine lung infection model provides a useful tool for both R. equi virulence and vaccine studies.
Copyright © 2014 Elsevier B.V. All rights reserved.
Publication Date: 2014-03-30 PubMed ID: 24852140DOI: 10.1016/j.vetmic.2014.03.026Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article focuses on the use of a mouse lung infection model to understand the virulence of Rhodococcus equi and test the effectiveness of vaccines. Rhodococcus equi is a pathogen which can cause severe lung infections specifically in foals and people with compromised immune systems.
Understanding the Research
- The researchers investigated a common mouse model used in studying Rhodococcus equi, a pathogenic bacterium that causes severe lung infections in foals and immunocompromised individuals.
- Even though mice are relatively resistant to Rhodococcus equi, they can serve as a useful model for in vivo (in the living organism) studies, especially if the infection is induced in a specific way.
- The most commonly employed model involves intravenous infection and checking the bacterial loads in the spleen and liver of the mice.
Investigating the Murine Lung for Experimental Infection
- The researchers used a specific quantity (10^7 CFU) of Rhodococcus equi to infect the lungs of BALB/c mice intranasally (through the nose).
- They discovered that virulent strains of Rhodococcus equi can survive consistently in quantifiable numbers in the lungs for up to 10 days, while strains that lack virulence are rapidly cleared from the lungs.
- This suggests that mice can be used as a model to study the degree of virulence of Rhodococcus equi and the ability of the host to clear the infection.
Developing an Internally Controlled Virulence Assay
- An assay was developed whereby different strains of Rhodococcus equi were inoculated and monitored within the same mouse.
- This competitive assay was used to compare bacteria lacking either the virulence plasmid vapA gene or the entire virulence plasmid.
- The loss of either of these two genetic elements did not significantly affect the ability of Rhodococcus equi to survive in the lung, which suggests that the single loss of the virulence factor VapA is sufficient to cause the full loss of virulence seen when the entire virulence plasmid is absent.
Testing Vaccine Efficacy
- The researchers tested the lung infection model by first vaccinating BALB/c mice with live Rhodococcus equi and then challenging them with virulent strains of the bacteria.
- This vaccination successfully protected the mice from acute pulmonary infection.
- The results of this study suggest that the murine lung model can be used as a valuable tool for studying the mechanisms of Rhodococcus equi virulence and the effectiveness of vaccines against it.
Cite This Article
APA
González-Iglesias P, Scortti M, MacArthur I, Hapeshi A, Rodriguez H, Prescott JF, Vazquez-Boland JA.
(2014).
Mouse lung infection model to assess Rhodococcus equi virulence and vaccine protection.
Vet Microbiol, 172(1-2), 256-264.
https://doi.org/10.1016/j.vetmic.2014.03.026 Publication
Researcher Affiliations
- Microbial Pathogenesis Unit, School of Biomedical Sciences and The Roslin Institute, University of Edinburgh, Edinburgh, UK.
- Microbial Pathogenesis Unit, School of Biomedical Sciences and The Roslin Institute, University of Edinburgh, Edinburgh, UK; Departamento de Bioquímica y Biología Molecular IV, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain. Electronic address: m.scortti@ed.ac.uk.
- Microbial Pathogenesis Unit, School of Biomedical Sciences and The Roslin Institute, University of Edinburgh, Edinburgh, UK.
- Microbial Pathogenesis Unit, School of Biomedical Sciences and The Roslin Institute, University of Edinburgh, Edinburgh, UK.
- Microbial Pathogenesis Unit, School of Biomedical Sciences and The Roslin Institute, University of Edinburgh, Edinburgh, UK; Irish Equine Centre, Johnstown, Naas, Ireland.
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Canada.
- Microbial Pathogenesis Unit, School of Biomedical Sciences and The Roslin Institute, University of Edinburgh, Edinburgh, UK.
MeSH Terms
- Actinomycetales Infections / immunology
- Actinomycetales Infections / microbiology
- Actinomycetales Infections / pathology
- Actinomycetales Infections / prevention & control
- Animals
- Bacterial Proteins / genetics
- Bacterial Proteins / immunology
- Bacterial Vaccines / administration & dosage
- Bacterial Vaccines / genetics
- Bacterial Vaccines / immunology
- Disease Models, Animal
- Female
- Lung / immunology
- Lung / pathology
- Mice
- Mice, Inbred BALB C
- Rhodococcus equi / genetics
- Rhodococcus equi / immunology
- Rhodococcus equi / pathogenicity
- Vaccination
- Virulence
- Virulence Factors / deficiency
- Virulence Factors / genetics
- Virulence Factors / immunology
Citations
This article has been cited 11 times.- Nielsen SS, Bicout DJ, Calistri P, Canali E, Drewe JA, Garin-Bastuji B, Gonzales Rojas JL, Gortázar C, Herskin M, Michel V, Miranda Chueca MÁ, Padalino B, Pasquali P, Roberts HC, Spoolder H, Ståhl K, Velarde A, Viltrop A, Winckler C, Baldinelli F, Broglia A, Kohnle L, Alvarez J. Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): antimicrobial-resistant Rhodococcus equi in horses. EFSA J 2022 Feb;20(2):e07081.
- Salazar-Rodríguez D, Aleaga-Santiesteban Y, Iglesias E, Plascencia-Hernández A, Pérez-Gómez HR, Calderón EJ, Vázquez-Boland JA, de Armas Y. Virulence Plasmids of Rhodococcus equi Isolates From Cuban Patients With AIDS. Front Vet Sci 2021;8:628239.
- Vázquez-Boland JA, Meijer WG. The pathogenic actinobacterium Rhodococcus equi: what's in a name?. Mol Microbiol 2019 Jul;112(1):1-15.
- Rocha JN, Dangott LJ, Mwangi W, Alaniz RC, Bordin AI, Cywes-Bentley C, Lawhon SD, Pillai SD, Bray JM, Pier GB, Cohen ND. PNAG-specific equine IgG(1) mediates significantly greater opsonization and killing of Prescottella equi (formerly Rhodococcus equi) than does IgG(4/7). Vaccine 2019 Feb 21;37(9):1142-1150.
- MacArthur I, Anastasi E, Alvarez S, Scortti M, Vázquez-Boland JA. Comparative Genomics of Rhodococcus equi Virulence Plasmids Indicates Host-Driven Evolution of the vap Pathogenicity Island. Genome Biol Evol 2017 May 1;9(5):1241-1247.
- Rofe AP, Davis LJ, Whittingham JL, Latimer-Bowman EC, Wilkinson AJ, Pryor PR. The Rhodococcus equi virulence protein VapA disrupts endolysosome function and stimulates lysosome biogenesis. Microbiologyopen 2017 Apr;6(2).
- Giles C, Ndi O, Barton MD, Vanniasinkam T. An Adenoviral Vector Based Vaccine for Rhodococcus equi. PLoS One 2016;11(3):e0152149.
- Valero-Rello A, Hapeshi A, Anastasi E, Alvarez S, Scortti M, Meijer WG, MacArthur I, Vázquez-Boland JA. An Invertron-Like Linear Plasmid Mediates Intracellular Survival and Virulence in Bovine Isolates of Rhodococcus equi. Infect Immun 2015 Jul;83(7):2725-37.
- Vazquez-Boland JA, Val-Calvo J, Duquesne F, Decorosi F, Viti C, Petry S, Scortti M. Rhodococcus parequi sp. nov., a new species isolated from equine farm soil closely related to the pathogen Rhodococcus equi. Int J Syst Evol Microbiol 2025 Mar;75(3).
- da Silveira BP, Cohen ND, Lawhon SD, Watson RO, Bordin AI. Protective immune response against Rhodococcus equi: An innate immunity-focused review. Equine Vet J 2025 May;57(3):563-586.
- Liu L, Cai P, Gu W, Duan X, Gao S, Ma X, Ma Y, Ma S, Li G, Wang X, Cai K, Wang Y, Cai T, Zhao H. Evaluation of vaccine candidates against Rhodococcus equi in BALB/c mice infection model: cellular and humoral immune responses. BMC Microbiol 2024 Jul 8;24(1):249.
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