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Topic:Rhodococcus equi
Rhodococcus equi is a bacterial pathogen that primarily affects foals, leading to pneumonia and other systemic infections. It is a significant concern in equine health due to its impact on the respiratory system of young horses. The bacterium is found in soil and can be inhaled by foals, leading to infection. Clinical signs of Rhodococcus equi infection in foals include coughing, fever, and respiratory distress. Diagnosis is typically confirmed through bacterial culture or polymerase chain reaction (PCR) testing. Management of the disease involves antimicrobial therapy and supportive care. This page compiles peer-reviewed research studies and scholarly articles that explore the pathogenesis, diagnosis, treatment, and prevention of Rhodococcus equi infections in horses.
Structural characterisation of the virulence-associated protein VapG from the horse pathogen Rhodococcus equi. Virulence and host range in Rhodococcus equi depends on the variable pathogenicity island of their virulence plasmids. Notable gene products are a family of small secreted virulence-associated proteins (Vaps) that are critical to intramacrophagic proliferation. Equine-adapted strains, which cause severe pyogranulomatous pneumonia in foals, produce a cell-associated VapA that is necessary for virulence, alongside five other secreted homologues. In the absence of biochemical insight, attention has turned to the structures of these proteins to develop a functional hypothesis. Recent studies have ...
Efficacy of gamithromycin for the treatment of foals with mild to moderate bronchopneumonia. Gamithromycin is active in vitro against the bacterial agents most commonly associated with bronchopneumonia in older foals. However, the clinical efficacy and safety of this drug have not been investigated. Objective: Gamithromycin is effective for the treatment of bronchopneumonia in foals. Methods: One hundred and twenty-one foals on a farm endemic for infections caused by Rhodococcus equi. Methods: In a controlled, randomized, and double blinded clinical trial, foals with ultrasonographic evidence of pulmonary abscesses (abscess score 8.0-20 cm) were randomly allocated in 3 treatment group...
Efficacy of liposomal gentamicin against Rhodococcus equi in a mouse infection model and colocalization with R. equi in equine alveolar macrophages. 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 r...
Validation and evaluation of VapA-specific IgG and IgG subclass enzyme-linked immunosorbent assays (ELISAs) to identify foals with Rhodococcus equi pneumonia. Rhodococcus equi (Rhodococcus hoagii/Prescottella equi) is a common cause of foal pneumonia, but its diagnosis remains a challenge for equine veterinarians. While the VapA-specific (virulence-associated protein A) immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) has low sensitivity and specificity for detecting pneumonic foals, little is known about VapA-specific IgG subclasses. Objective: To evaluate the performance of VapA-specific ELISA for IgG and its subclasses IgGa, IgGb and IgG(T) in the early diagnosis of pneumonia caused by R. equi. Methods: Assay validation follow...
VapA-specific IgG and IgG subclasses responses after natural infection and experimental challenge of foals with Rhodococcus equi. Rhodococcus equi is a common cause of pneumonia in young foals worldwide and has considerable economic effects on the global equine industry. Despite ongoing efforts, no vaccine is currently available to prevent rhodococaal pneumonia. This is due, in part, to an incomplete understanding of the protective immune response to this bacterium. While antibodies to VapA, a lipoprotein produced by virulent R. equi, are useful in differentiating antibody production in response to pathogenic versus non-pathogenic strains, the significance of the humoral response of foals to this lipoprotein remains poor...
Update on bacterial pneumonia in the foal and weanling. Bacterial pneumonia is a common cause of disease in both neonatal and weanling foals. The causal organism or organisms differ with the age of the foal, should be identified via microbiologic culture, and will ultimately dictate appropriate treatment. Initial treatment in neonates should be broad spectrum and bactericidal, whereas weanling age foals may receive more targeted treatment. The combination of a macrolide antibiotic and rifampin remains the gold standard for treatment of Rhodococcus equi pneumonia; however, resistance to these antimicrobials is a concern.
The development of equine immunity: Current knowledge on immunology in the young horse. The development of equine immunity from the fetus to adulthood is complex. The foal's immune response and the immune mechanisms that they are equipped with, along with changes over the first months of life until the immune system becomes adult-like, are only partially understood. While several innate immune responses seem to be fully functional from birth, the onset of adaptive immune response is delayed. For some adaptive immune parameters, such as immunoglobin (Ig)G1, IgG3, IgG5 and IgA antibodies, the immune response starts before or at birth and matures within 3 months of life. Other antib...
Rhodococcus equi pneumonia in foals: an assessment of the early diagnostic value of serum amyloid A and plasma fibrinogen concentrations in equine clinical practice. Early diagnosis and prevention of Rhodococcus equi pneumonia in foals represent important goals for equine clinicians. Recent protocols for diagnosis and treatment of Rhodococcosis in foals typically rely on a multimodal approach based on sonographic evidence suggestive of pyogranulomas, sonographic abscess scores and laboratory findings including plasma fibrinogen concentrations, blood biochemistry testing and platelet and leukocyte counts. The aim of this study was to assess the utility of weekly testing of serum amyloid A (SAA) and plasma fibrinogen concentrations in foals to achieve early ...
Rhodococcus equi pneumonia in foals: an assessment of the early diagnostic value of serum amyloid A and plasma fibrinogen concentrations in equine clinical practice. Early diagnosis and prevention of Rhodococcus equi pneumonia in foals represent important goals for equine clinicians. Recent protocols for diagnosis and treatment of Rhodococcosis in foals typically rely on a multimodal approach based on sonographic evidence suggestive of pyogranulomas, sonographic abscess scores and laboratory findings including plasma fibrinogen concentrations, blood biochemistry testing and platelet and leukocyte counts. The aim of this study was to assess the utility of weekly testing of serum amyloid A (SAA) and plasma fibrinogen concentrations in foals to achieve early ...
In contrast to other species, α-Galactosylceramide (α-GalCer) is not an immunostimulatory NKT cell agonist in horses. α-GalCer is a potent immunomodulatory molecule that is presented to NKT cells via the CD1 antigen-presenting system. We hypothesized that when used as an adjuvant α-GalCer would induce protective immune responses against Rhodococcus equi, an important pathogen of young horses. Here we demonstrate that the equine CD1d molecule shares most features found in CD1d from other species and has a suitable lipid-binding groove for presenting glycolipids to NKT cells. However, equine CTL stimulated with α-GalCer failed to kill cells infected with R. equi, and α-GalCer did not increase killing by C...
Intramuscular administration of a synthetic CpG-oligodeoxynucleotide modulates functional responses of neutrophils of neonatal foals. Neutrophils play an important role in protecting against infection. Foals have age-dependent deficiencies in neutrophil function that may contribute to their predisposition to infection. Thus, we investigated the ability of a CpG-ODN formulated with Emulsigen to modulate functional responses of neutrophils in neonatal foals. Eighteen foals were randomly assigned to receive either a CpG-ODN with Emulsigen (N = 9) or saline intramuscularly at ages 1 and 7 days. At ages 1, 3, 9, 14, and 28, blood was collected and neutrophils were isolated from each foal. Neutrophils were assessed for basal and R...
Rhodococcus equi foal pneumonia. Pneumonia caused by Rhodococcus equi is an important cause of disease and death in foals. This article reviews current knowledge of the epidemiology, clinical signs, diagnosis, treatment, prevention, and control of R equi pneumonia in foals.
Rhodococcus equi (Prescottella equi) vaccines; the future of vaccine development. For decades researchers have been targeting prevention of Rhodococcus equi (Rhodococcus hoagui/Prescottella equi) by vaccination and the horse breeding industry has supported the ongoing efforts by researchers to develop a safe and cost effective vaccine to prevent disease in foals. Traditional vaccines including live, killed and attenuated (physical and chemical) vaccines have proved to be ineffective and more modern molecular-based vaccines including the DNA plasmid, genetically attenuated and subunit vaccines have provided inadequate protection of foals. Newer, bacterial vector vaccines hav...
Immunogenicity of an electron beam inactivated Rhodococcus equi vaccine in neonatal foals. Rhodococcus equi is an important pathogen of foals that causes severe pneumonia. To date, there is no licensed vaccine effective against R. equi pneumonia of foals. The objectives of our study were to develop an electron beam (eBeam) inactivated vaccine against R. equi and evaluate its immunogenicity. A dose of eBeam irradiation that inactivated replication of R. equi while maintaining outer cell wall integrity was identified. Enteral administration of eBeam inactivated R. equi increased interferon-γ production by peripheral blood mononuclear cells in response to stimulation with virulent R. ...
Pharmacokinetics, pulmonary disposition and tolerability of liposomal gentamicin and free gentamicin in foals. Although gentamicin is highly active against Rhodococcus equi in vitro, its clinical efficacy has been limited presumably due to poor cellular uptake. Encapsulation of drugs in liposomes enhances their cellular uptake. Objective: To compare the disposition of liposomal gentamicin (LG) and free gentamicin (FG) in the plasma, pulmonary epithelial lining fluid and bronchoalveolar cells of healthy foals after i.v. administration or by nebulisation, and to assess the tolerability of the drug after repeated i.v. dosing. Methods: Experimental study. Methods: Eight healthy foals received a single i.v....
Administration of commercial Rhodococcus equi specific hyperimmune plasma results in variable amounts of IgG against pathogenic bacteria in foals. Rhodococcus equi is the most common cause of pneumonia in young foals. A vaccine is not available and the use of R equi-specific hyperimmune plasma (HIP) is common. Despite its widespread use, the efficacy of HIP in preventing disease remains controversial. The objectives of this study were (1) to evaluate the virulence associate protein A (VapA)-specific IgG and IgG subclasses in commercially available R equi HIP and (2) to evaluate serum VapA-specific IgG and IgG subclasses in foals following administration of commercial R equi HIP. Three different lots from four commercial R equi HIP were s...
Morphometric examination of the equine adult and foal lung. To understand the mechanisms of airway inflammation associated with equine diseases such as Rhodococcus equi infection, we must identify baseline "normal" structural characteristics of the horse lung. To develop a detailed understanding of the morphology of the horse lung, we adapted and applied stereological methods to the lungs from healthy adult horses (N = 4) and 1-day (N = 5) and 30-day (N = 5) old foals. The left lung was fixed in situ by intrabronchial instillation of glutaraldehyde/paraformaldehyde fixative at 25 cm H2 O column and sampled using a fractionator design follow...
Identification of genomic loci associated with Rhodococcus equi susceptibility in foals. Pneumonia caused by Rhodococcus equi is a common cause of disease and death in foals. Although agent and environmental factors contribute to the incidence of this disease, the genetic factors influencing the clinical outcomes of R. equi pneumonia are ill-defined. Here, we performed independent single nucleotide polymorphism (SNP)- and copy number variant (CNV)-based genome-wide association studies to identify genomic loci associated with R. equi pneumonia in foals. Foals at a large Quarter Horse breeding farm were categorized into 3 groups: 1) foals with R. equi pneumonia (clinical group [N = ...
The effectiveness of anti-R. equi hyperimmune plasma against R. equi challenge in thoroughbred Arabian foals of mares vaccinated with R. equi vaccine. This study aimed to determine the effectiveness of a pregnant mare immunization of a Rhodococcus equi (R. equi) vaccine candidate containing a water-based nanoparticle mineral oil adjuvanted (Montanide IMS 3012) inactive bacterin and virulence-associated protein A (VapA), as well as the administration of anti-R. equi hyperimmune (HI) plasma against R. equi challenge in the mares' foals. The efficacy of passive immunizations (colostral passive immunity by mare vaccination and artificial passive immunity by HI plasma administration) was evaluated based on clinical signs, complete blood count, bl...
Mouse lung infection model to assess Rhodococcus equi virulence and vaccine protection. 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 lun...
Effects of age and macrophage lineage on intracellular survival and cytokine induction after infection with Rhodococcus equi. Rhodococcus equi, a facultative intracellular pathogen of macrophages, causes life-threatening pneumonia in foals and in people with underlying immune deficiencies. As a basis for this study, we hypothesized that macrophage lineage and age would affect intracellular survival of R. equi and cytokine induction after infection. Monocyte-derived and bronchoalveolar macrophages from 10 adult horses and from 10 foals (sampled at 1-3 days, 2 weeks, 1 month, 3 months, and 5 months of age) were infected ex vivo with virulent R. equi. Intracellular R. equi were quantified and mRNA expression of IL-1β, ...
Comparative genomic analyses reveal a lack of a substantial signature of host adaptation in Rhodococcus equi (‘Prescottella equi’). Rhodococcus equi ('Prescottella equi') is a pathogenic actinomycete primarily infecting horses but has emerged as an opportunistic human pathogen. We have sequenced the genome of the type strain of this species, R. equi strain C7(T) , and compared the genome with that of another foal isolate 103S and of a human isolate ATCC 33707. The R. equi strains are closely related to each other and yet distantly related to other rhodococci and Nocardia brasiliensis. The comparison of gene contents among R. equi strains revealed minor differences that could be associated with host adaptation from foals to...
Analyses of lipid rafts, Toll-like receptors 2 and 4, and cytokines in foals vaccinated with Virulence Associated Protein A/CpG oligonucleotide vaccine against Rhodococcus equi. Rhodococcus equi establishes long-term pulmonary infection, survives in phagolysosomes of alveolar macrophages and causes pneumonia in foals. The failure of the foal to clear R. equi bacteria is believed to be due to its inability to produce IFN-γ and defects in Toll-like receptor(TLR) signaling. Lipid rafts sequester immune receptors such as TLRs and facilitate efficient cell signaling and therefore, a deficiency in accumulation of receptors in lipid rafts may result in failure to activate. We tested whether a Virulence Associated Protein A (VapA)/CpG vaccine against R. equi would impact the...
In vitro effectiveness of the antimicrobial peptide eCATH1 against antibiotic-resistant bacterial pathogens of horses. The equine antimicrobial peptide eCATH1 previously has been shown to have in vitro activity against antibiotic-susceptible reference strains of Rhodococcus equi and common respiratory bacterial pathogens of foals. Interestingly, eCATH1 was also found to be effective in the treatment of R. equi infection induced in mice. The aim of this study was to assess the in vitro activity of eCATH1 against equine isolates of Gram-negative (Escherichia coli, Salmonella enterica, Klebsiella pneumoniae and Pseudomonas spp.) and Gram-positive (R. equi, Staphylococcus aureus) bacteria resistant to multiple cla...
Assessment of the safety and immunogenicity of Rhodococcus equi-secreted proteins combined with either a liquid nanoparticle (IMS 3012) or a polymeric (PET GEL A) water-based adjuvant in adult horses and foals–identification of promising new candidate antigens. Rhodococcus equi is the most common infectious cause of mortality in foals between 1 and 6 months of age. Because of an increase in the number of antibiotic-resistant strains, the optimization of a prophylactic strategy is a key factor in the comprehensive management of R. equi pneumonia. The objectives of this study were to assess the safety and immunogenicity of R. equi-secreted proteins (ReSP) co-administered with either the nanoparticular adjuvant Montanide™ IMS 3012 VG, or a new polymeric adjuvant Montanide™ PET GEL A, and to further investigate the most immunogenic proteins for subse...
Systemic and respiratory oxidative stress in the pathogenesis and diagnosis of Rhodococcus equi pneumonia. Oxidative stress (OS) is most simply defined as an imbalance between oxidants and antioxidants. Oxidative stress has been suggested to play roles in various equine respiratory diseases and the significance of OS in the pathogenesis of Rhodococcus equi pneumonia is unknown. Objective: To measure and relate biomarkers of OS to lesions consistent with R. equi pneumonia. Methods: Case-control study. Methods: Various OS biomarkers were measured from blood and exhaled breath condensate (EBC) samples collected from 26 foals between 1 and 2 months of age (n = 12 cases and n = 14 controls) on 2 Thoro...
MICs of 32 antimicrobial agents for Rhodococcus equi isolates of animal origin. The aim of this study was to determine the MICs of 32 antimicrobial agents for 200 isolates of Rhodococcus equi of animal origin by applying a recently described broth microdilution protocol, and to investigate isolates with distinctly elevated rifampicin MICs for the genetic basis of rifampicin resistance. Methods: The study included 200 R. equi isolates, including 160 isolates from horses and 40 isolates from other animal sources, from the USA and Europe. MIC testing of 32 antimicrobial agents or combinations thereof followed a recently published protocol. A novel PCR protocol for the joint ...
The equine CD1 gene family is the largest and most diverse yet identified. The CD1 family is a group of non-polymorphic MHC class I-like molecules that present lipid-based antigens to T cells. Previous work in our laboratory demonstrated that cytotoxic T lymphocytes from immune adult horses recognize lipids from the cell wall of an important equine pathogen, Rhodococcus equi. These findings suggest an important role for the equine CD1 antigen presentation system in protective immune responses to microbial pathogens in the horse. In this study, we characterized and mapped the equine CD1 gene cluster. The equine genome was found to contain 13 complete CD1 genes; seven ...
Study of lysozyme resistance in Rhodococcus equi. Lysozyme is an important and widespread component of the innate immune response that constitutes the first line of defense against bacterial pathogens. The bactericidal effect of this enzyme relies on its capacity to hydrolyze the bacterial cell wall and also on a nonenzymatic mechanism involving its cationic antimicrobial peptide (CAMP) properties, which leads to membrane permeabilization. In this paper, we report our findings on the lysozyme resistance ability of Rhodococcus equi, a pulmonary pathogen of young foals and, more recently, of immunocompromised patients, whose pathogenic capacity...
Failure of a VapA/CpG oligodeoxynucleotide vaccine to protect foals against experimental Rhocococcus equi pneumonia despite induction of VapA-specific antibody and interferon-γ response. We evaluated the immunogenic and protective potential of a recombinant VapA/CpG oligodeoxynucleotide (ODN) 2395 vaccine in neonatal foals undergoing experimental Rhodococcus equi challenge. Foals (n = 8) were vaccinated by intramuscular injection on days 1 and 15 of the study; control foals (n = 7) received a phosphate-buffered saline (PBS) solution. All foals were challenged by intrabronchial administration of 5 × 10⁶ R. equi 103⁺ on day 29. Bronchoalveolar lavages were done on days 15, 29, and 36 and total cell count, differential cell count, rVapA-stimulated cell proliferation and inte...
