Efficacy of liposomal gentamicin against Rhodococcus equi in a mouse infection model and colocalization with R. equi in equine alveolar macrophages.
Abstract: Rhodococcus equi, a facultative intracellular pathogen and an important cause of pneumonia in foals, is highly susceptible to killing by gentamicin in vitro. However, gentamicin is not effective in vivo, due to its poor cellular penetration. Encapsulation of drugs in liposomes enhances cellular uptake. The objectives of this study were to compare liposomal gentamicin and free gentamicin with respect to their uptake by equine macrophages and intracellular colocalization with R. equi and to compare the efficacies of liposomal gentamicin, free gentamicin and clarithromycin with rifampin for the reduction of R. equi CFU in a mouse model of infection. After ex vivo exposure, a significantly higher mean (±SD) percentage of equine alveolar macrophages contained liposomal gentamicin (91.9±7.6%) as opposed to free gentamicin (16.8±12.5%). Intracellular colocalization of drug and R. equi, as assessed by confocal microscopy, occurred in a significantly higher proportion of cells exposed to liposomal gentamicin (81.2±17.8%) compared to those exposed to free gentamicin (10.4±8.7%). The number of R. equi CFU in the spleen was significantly lower in mice treated with liposomal gentamicin compared to that of mice treated with free gentamicin or to untreated control mice. Treatment with liposomal gentamicin also resulted in a significantly greater reduction in the number of R. equi CFU in the liver compared to treatment with clarithromycin in combination with rifampin. These results support further investigation of liposomal gentamicin as a new treatment for infections caused by R. equi.
Copyright © 2015 Elsevier B.V. All rights reserved.
Publication Date: 2015-01-27 PubMed ID: 25666452DOI: 10.1016/j.vetmic.2015.01.015Google 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.
This study evaluates the effectiveness of liposomal gentamicin compared to free gentamicin and a popular antibiotic cocktail in eliminating Rhodococcus equi bacteria in a mouse model. The researchers found that liposomal gentamicin was considerably better at penetrating cells and co-locating with the bacteria, and as a result, it significantly reduced the bacterial levels in the spleen and liver of infected mice.
Understanding Rhodococcus equi and the role of gentamicin
- Rhodococcus equi is a type of bacteria that primarily causes pneumonia in young foals. While it’s highly susceptible to a common antibiotic called gentamicin in a controlled laboratory environment, the same effect cannot be replicated in a real-life situation due to gentamicin’s inability to infiltrate living cells.
Research objectives and methods
- The researchers investigated whether encapsulating gentamicin into small, fat-like particles called liposomes might enhance its cellular uptake and increase its effectiveness against R. equi.
- They carried out the study using a mouse model of R. equi infection and also tested the uptake and co-localization (sharing of space) of liposomal gentamicin and free gentamicin within equine macrophages, a type of white blood cells that are vital for immune defense.
Results and key findings
- It was found that a much higher percentage of equine alveolar macrophages contained liposomal gentamicin compared to free gentamicin when exposed ex vivo (outside the living organism).
- Confocal microscopy, a tool for creating sharp two or three-dimensional images, revealed that liposomal gentamicin co-localized with R. equi in a significantly larger proportion of cells than free gentamicin.
- When applied in the mouse model of infection, liposomal gentamicin resulted in a dramatic reduction of R. equi CFUs (colony-forming units or viable bacteria count) in the spleen compared to free gentamicin or no treatment at all.
- The gentamicin liposomes also proved significantly more effective than the combined antibiotic treatment of clarithromycin and rifampin in reducing the number of R. equi CFUs in the liver.
Implications and future directions
- The results suggest that gentamicin’s poor penetration into cells, which hampers its effect on R. equi, can be significantly improved by packing it into liposomes. Consequently, the superior efficacy of liposomal gentamicin warrants further research into its potential as a novel treatment for infections caused by R. equi.
Cite This Article
APA
Burton AJ, Giguère S, Berghaus LJ, Hondalus MK, Arnold RD.
(2015).
Efficacy of liposomal gentamicin against Rhodococcus equi in a mouse infection model and colocalization with R. equi in equine alveolar macrophages.
Vet Microbiol, 176(3-4), 292-300.
https://doi.org/10.1016/j.vetmic.2015.01.015 Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States. Electronic address: gigueres@uga.edu.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
- Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
- Department of Drug Discovery & Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, United States.
MeSH Terms
- Actinomycetales Infections / drug therapy
- Actinomycetales Infections / microbiology
- Actinomycetales Infections / veterinary
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / pharmacology
- Clarithromycin / pharmacology
- Disease Models, Animal
- Gentamicins / administration & dosage
- Gentamicins / pharmacology
- Horse Diseases / drug therapy
- Horse Diseases / microbiology
- Horses
- Liposomes
- Liver / microbiology
- Macrophages, Alveolar / microbiology
- Male
- Mice
- Mice, Nude
- Pneumonia / drug therapy
- Pneumonia / microbiology
- Pneumonia / veterinary
- Rhodococcus equi / drug effects
- Rifampin / pharmacology
- Spleen / microbiology
Citations
This article has been cited 14 times.- Suzuki Y, Sakaizawa N, Takai S, Kubota H, Hasegawa N, Sasaki Y, Kakuda T. An Autobioluminescent Method for Evaluating In Vitro and In Vivo Growth of Rhodococcus equi. Microbiol Spectr 2022 Jun 29;10(3):e0075822.
- Rivolta AA, Pittman DC, Kappes AJ, Stancil RK, Kogan C, Sanz MG. The type of anticoagulant used for plasma collection affects in vitro Rhodococcus equi assays. BMC Res Notes 2022 Feb 14;15(1):50.
- Nakhaei P, Margiana R, Bokov DO, Abdelbasset WK, Jadidi Kouhbanani MA, Varma RS, Marofi F, Jarahian M, Beheshtkhoo N. Liposomes: Structure, Biomedical Applications, and Stability Parameters With Emphasis on Cholesterol. Front Bioeng Biotechnol 2021;9:705886.
- Vail KJ, da Silveira BP, Bell SL, Cohen ND, Bordin AI, Patrick KL, Watson RO. The opportunistic intracellular bacterial pathogen Rhodococcus equi elicits type I interferon by engaging cytosolic DNA sensing in macrophages. PLoS Pathog 2021 Sep;17(9):e1009888.
- Mourenza Á, Gil JA, Mateos LM, Letek M. A Novel Screening Strategy Reveals ROS-Generating Antimicrobials That Act Synergistically against the Intracellular Veterinary Pathogen Rhodococcus equi. Antioxidants (Basel) 2020 Jan 28;9(2).
- Ruocco NA 3rd, Luedke LK, Fortier LA, Ducharme NG, Reesink HL. Rhodococcus equi Joint Sepsis and Osteomyelitis Is Associated With a Grave Prognosis in Foals. Front Vet Sci 2019;6:503.
- Bujold AR, Lani NR, Sanz MG. Strain-to-strain variation of Rhodococcus equi growth and biofilm formation in vitro. BMC Res Notes 2019 Aug 19;12(1):519.
- Willingham-Lane JM, Berghaus LJ, Berghaus RD, Hart KA, Giguère S. Effect of Macrolide and Rifampin Resistance on Fitness of Rhodococcus equi during Intramacrophage Replication and In Vivo. Infect Immun 2019 Oct;87(10).
- Rampacci E, Marenzoni ML, Chiaradia E, Passamonti F, Ricci M, Pepe M, Coletti M, Giovagnoli S. In vitro performances of novel co-spray-dried azithromycin/rifampicin microparticles for Rhodococcus equi disease treatment. Sci Rep 2018 Aug 14;8(1):12149.
- Wright LM, Carpinone EM, Bennett TL, Hondalus MK, Starai VJ. VapA of Rhodococcus equi binds phosphatidic acid. Mol Microbiol 2018 Feb;107(3):428-444.
- Cohen ND, Giguère S, Burton AJ, Rocha JN, Berghaus LJ, Brake CN, Bordin AI, Coleman MC. Use of Liposomal Gentamicin for Treatment of 5 Foals with Experimentally Induced Rhodococcus equi Pneumonia. J Vet Intern Med 2016 Jan-Feb;30(1):322-5.
- Boneva-Marutsova B, Marutsov P, Kerner K, Zhelev G. First Detection of Rhodococcus equi in a Foal in Bulgaria-A Case Report. Animals (Basel) 2025 Jul 12;15(14).
- Tang L, Yang X, He L, Zhu C, Chen Q. Preclinical advance in nanoliposome-mediated photothermal therapy in liver cancer. Lipids Health Dis 2025 Jan 31;24(1):31.
- da Silveira BP, Barhoumi R, Bray JM, Cole-Pfeiffer HM, Mabry CJ, Burghardt RC, Cohen ND, Bordin AI. Impact of surface receptors TLR2, CR3, and FcγRIII on Rhodococcus equi phagocytosis and intracellular survival in macrophages. Infect Immun 2024 Jan 16;92(1):e0038323.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
