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Rhodococcus equi

Rhodococcus equi (also known as Prescottella equi in some recent classifications) is a soil-dwelling, Gram-positive, facultative intracellular actinomycete bacterium that primarily causes pyogranulomatous pneumonia in young foals and serves as an opportunistic pathogen in immunocompromised humans, leading to subacute necrotizing pulmonary infections and extrapulmonary disease. It is classified within the family Nocardiaceae and was originally named Corynebacterium equi before reclassification to the genus Rhodococcus in 1977 due to its distinct genetic and phenotypic traits. The bacterium is strictly aerobic, non-motile, and pleomorphic, often appearing as coccobacilli; it is partially acid-fast, non-spore-forming, and produces characteristic orange-salmon pigmented colonies on agar after prolonged incubation. R. equi thrives in environments rich in , such as , hay, and the of herbivores, particularly , where it can persist for extended periods under favorable conditions like warm, dry, and weather. occurs mainly through of contaminated particles from these sources, with over 50% of cases linked to exposure to farm animals or environments with high levels. Its consists of a 5.04 megabase with a high G+C content of 68.8% and often includes an 80.6 kb (e.g., pVAPA) that encodes key pathogenicity factors. In , R. equi is a major cause of in foals under six months of age, resulting in formation and high mortality if untreated; is endemic in horse-breeding regions worldwide, excluding . in foals is driven by plasmid-encoded proteins like VapA, which enable the bacterium to survive and replicate within macrophages by altering maturation and evading lysosomal fusion. In humans, infections are rare but increasingly reported, predominantly affecting those with (accounting for about 61.5% of cases in a 2010 review), transplant recipients, or other immunosuppressive conditions; manifestations include cavitary , bacteremia, and wound infections, mimicking . Treatment of R. equi infections typically requires prolonged antimicrobial therapy due to its intracellular lifestyle and intrinsic resistance mechanisms, such as β-lactamases and efflux pumps; effective agents include (e.g., erythromycin), rifampicin, and , often combined for synergistic effects in both animal and cases. Epidemiologically, the bacterium's zoonotic potential underscores the importance of preventive measures like dust control in equine facilities and early in at-risk populations.

Taxonomy and Classification

Historical Nomenclature

Rhodococcus equi was first isolated in 1923 by Swedish veterinarian Hilding Magnusson from the lungs of foals affected by pyogranulomatous pneumonia, a condition characterized by suppurative inflammation and granuloma formation in the respiratory tract. Magnusson named the organism Corynebacterium equi owing to its Gram-positive, rod-shaped morphology and irregular arrangement, which resembled other members of the Corynebacterium genus known at the time. This initial classification reflected the limited taxonomic tools available, focusing primarily on microscopic appearance and basic staining properties. Subsequent isolations and studies revealed discrepancies with typical corynebacteria, leading to intermediate reclassifications based on emerging phenotypic observations. In 1944, G.E. Turfitt described a cholesterol-degrading strain as Proactinomyces restrictus, highlighting its actinomycete-like growth and restricted metabolic capabilities. By 1957, R.E. Gordon and J.M. Mihm proposed Nocardia restricta for similar isolates, citing branching filaments, partial due to mycolic acid-containing s, and colony that aligned more closely with nocardioform than simple rods. These shifts were driven by recognition of the organism's complex composition, including long-chain mycolic acids, and its variable —from rods in young cultures to coccoid forms and fragmented filaments in older ones—which did not fit neatly within Corynebacterium or early Nocardia definitions. The modern nomenclature was established in 1977 when M. Goodfellow and G. Alderson transferred the species to the newly proposed genus Rhodococcus as Rhodococcus equi, emending the original description to emphasize its placement within the "rhodochrous" complex of actinomycetes. This reclassification was justified by comprehensive phenotypic analyses, including , whole-cell profiles, and cell wall chemotypes showing meso-diaminopimelic acid and , alongside mycolic acids structurally intermediate between those of and . The genus name reflected the organism's frequent production of orange-red pigments (from "rhodo" for red and "coccus" for its spherical elements) and distinguished it from related genera through its nonmotile, nonspore-forming nature and aerobic metabolism. Later molecular confirmation via 16S rRNA gene sequencing in the 1980s further validated this position, demonstrating close phylogenetic affiliation with other rhodococci while excluding it from and . Pivotal works include Magnusson's foundational 1923 report and Goodfellow and Alderson's 1977 proposal, which resolved decades of taxonomic ambiguity through integrated morphological, chemical, and genetic evidence.

Current Status and Debates

_Rhodococcus equi is currently classified within the genus Rhodococcus of the family Nocardiaceae, order Actinomycetales, and phylum Actinobacteria, a positioning supported by genomic features such as a G+C content of approximately 68-70% and the presence of mycolic acids in its cell wall, alongside phenotypic traits like catalase positivity and utilization of specific carbon sources. This taxonomic placement has faced challenges from proposed reclassifications highlighting its phylogenetic distinction from other species. In 2014, Kämpfer et al. suggested reclassifying Rhodococcus equi and the related Corynebacterium hoagii as Rhodococcus hoagii comb. nov., based on 16S rRNA sequence similarities and chemotaxonomic data emphasizing shared profiles but divergent phenotypic traits from environmental rhodococci. In 2013, Jones et al. proposed the novel Prescottella with Prescottella equi comb. nov. for equine-associated strains (validly published in ), arguing for separation due to distinct phylogenetic clustering in multi- analyses, including average nucleotide identity (ANI) values below 95% with non-pathogenic Rhodococcus species, and unique adaptations for zoonotic transmission. These proposals underscore R. equi's closer relation to pathogenic actinomycetes than to saprophytic rhodococci, previously known as Corynebacterium equi before its 1977 transfer to Rhodococcus. Arguments in favor of reclassification include (MLST) data from Duquesne et al. (2017), which delineated R. equi into distinct sequence types separated from non-pathogenic by significant allelic differences in housekeeping genes like gyrB and , supporting its evolutionary divergence. Opposing views emphasize nomenclatural stability for clinical and veterinary applications, noting that reclassifications could disrupt established diagnostic protocols and epidemiological tracking, with 2022 genomic studies by et al. confirming zoonotic lineage divergence through analysis revealing unique islands absent in environmental strains, yet advocating retention of the original name to avoid confusion. More recent phylogenomic analyses, such as those by Val-Calvo and Vázquez-Boland (2023), have proposed reclassifying Prescottella species back into the genus using network analysis-aided, context-uniform approaches to address genus over-splitting in Mycobacteriales, influencing ongoing 2025 discussions. As of 2025, the International Committee on Systematics of Prokaryotes (ICSP) maintains consensus on retaining Rhodococcus equi as the valid name, following the 2021 Judicial Commission Opinion 106 that conserved it over R. hoagii and clarified Prescottella equi as an alternative but non-preferred pending comprehensive whole-genome sequencing to resolve ongoing phylogenetic debates. Recent surveys, such as those in 2025, continue to use R. equi in phylogenetic contexts, reflecting practical consensus despite NCBI's preference for Prescottella equi.

Morphology and Habitat

Cellular Characteristics

Rhodococcus equi is a Gram-positive, non-motile, non-spore-forming measuring approximately 0.5-1 μm in width and 1-5 μm in length, often appearing as diplobacilli or short rods under microscopic examination. The bacterium exhibits pleomorphic , transitioning from coccoid to rod-like or filamentous forms depending on growth conditions. It is strictly aerobic, with optimal growth occurring at temperatures between 30°C and 37°C on media such as blood agar, where it forms smooth, mucoid, non-hemolytic colonies that develop a characteristic salmon-pink pigmentation after 48-72 hours of . Biochemically, R. equi is catalase-positive, urease-positive, and typically , though some strains show variable activity. The cell wall of R. equi features a high lipid content, including mycolic acids with chain lengths ranging from 30 to 54 carbon atoms, covalently linked to an layer, which contributes to its nocardioform structure. This composition imparts partial , particularly when observed in tissue samples, though routine acid-fast staining is often negative. Multidrug resistance in R. equi is facilitated by mechanisms such as efflux pumps and production of β-lactamases. Metabolically, R. equi is versatile, capable of utilizing via cholesterol oxidase activity and degrading hydrocarbons, reflecting its actinomycete heritage. It also produces and is capable of synergistic in the presence of other (CAMP test positive), aiding in its physiological adaptations. These traits support its facultative intracellular lifestyle within host cells.

Environmental Distribution

Rhodococcus equi is a ubiquitous soil bacterium found worldwide in alkaline and neutral pH environments, particularly in dry, dusty areas contaminated with herbivore feces such as horse paddocks and stables. It has been isolated from diverse environmental sources including hay, sawdust, water, air, and animal feeds, with higher prevalence in equine farm settings where fecal contamination enriches the soil. Concentrations in soil typically range from 10^2 to 10^5 colony-forming units (CFU) per gram, while airborne concentrations on farms typically range from 0 to 10 CFU per 1000 L of air in stables during peak seasons, with higher values in dusty conditions. The bacterium persists in these niches for over 12 months, aided by its ability to form biofilms that protect against desiccation and ultraviolet radiation. Persistence in the is enhanced by sources from , where R. equi utilizes sterols such as derived from plant materials as a primary carbon and energy source. It demonstrates broad , surviving from -5°C to 40°C and growing optimally between 10°C and 40°C, which allows proliferation in temperate and arid climates. Environmental strains often lack the virulence plasmid found in pathogenic isolates, enabling to free-living conditions through chromosomal genes supporting stress responses. Genomic analyses of environmental and virulent strains reveal adaptations for survival, including core genes for resistance (e.g., ) and nutrient metabolism that facilitate persistence in fluctuating conditions. A 2022 pan-genome study of 53 strains highlighted 3,690 core genes involved in transcription, , and environmental stress responses, distinguishing non-pathogenic -adapted variants from those associated with equine hosts. Transmission to susceptible hosts occurs primarily through of contaminated dust from these environments.

Hosts and Epidemiology

Animal Hosts

Rhodococcus equi primarily infects foals aged 1 to 6 months, causing pyogranulomatous characterized by formation in the lungs and associated nodes. This , often referred to as rhodococcal , leads to significant morbidity on endemic farms, with clinical rates typically ranging from 5% to 20% of foals, though rates exceeding 40% have been reported in severe outbreaks. The manifests as suppurative with formation, primarily affecting the pulmonary and draining lymphatics, and foals may present with respiratory distress, fever, and . Epidemiologically, infections peak seasonally in late spring and summer, coinciding with foaling seasons in both hemispheres and increased environmental bacterial loads. Risk factors include farm , which facilitates higher bacterial exposure, and dust-laden environments that promote of the . Recent farm-based studies from 2020 to 2025 indicate seroprevalence reaching up to 25% in high-risk populations in endemic regions, underscoring the 's persistence in breeding operations. Susceptibility in young stems from their immature adaptive immunity, particularly deficient function, allowing intracellular bacterial proliferation. Transmission occurs primarily through inhalation of aerosolized R. equi from contaminated , , and in the farm , with no evidence of direct horse-to-horse spread. Infected foals shed the bacterium in their , perpetuating environmental contamination and establishing endemic cycles on farms worldwide. Beyond equids, R. equi infects a range of domestic and wild animals, though less frequently and often subclinically. In pigs, it causes and lymphadenitis with granulomatous lesions in mesenteric s. Goats develop pyogranulomatous abscesses, particularly in the liver and lungs, as seen in case reports of disseminated infections. Cattle experience rare cases of cervical or mesenteric lymphadenitis mimicking , while wild boars suffer and abscesses, contributing to environmental reservoirs. These infections highlight R. equi's zoonotic potential through shared contaminated habitats, though veterinary impacts are most pronounced in foals.

Human Infections

Rhodococcus equi causes rare zoonotic infections in humans, with the first case reported in 1967 and a marked increase in reports since the , coinciding with the epidemic. By the end of 2024, a comprehensive search identified 346 documented cases worldwide. These infections predominantly affect immunocompromised individuals, including those with (accounting for approximately 60% of cases), solid organ or bone marrow transplant recipients, patients with malignancies such as or , and those on immunosuppressive therapies like corticosteroids or . Key risk factors include underlying and occupational exposure to contaminated environments, such as veterinarians, farmers, and handlers who inhale dust or aerosols from enriched with equine . A 2022 CDC report highlighted the international spread of multidrug-resistant R. equi strains originating from equine sources , with detection in Ireland linked to imported s, underscoring the zoonotic transmission pathway from animal reservoirs. No evidence supports person-to-person spread, emphasizing environmental acquisition as the primary mode. Incidence remains low overall, representing less than 1% of bacterial pneumonias among at-risk immunocompromised groups, though rates are higher in regions endemic for equine infections, such as horse-breeding farms. Recent studies from 2024 document a rising trend in cases among non-HIV immunocompromised patients, including those with hematologic malignancies or post-transplant status, potentially due to improved diagnostics and broader immunosuppressive practices. Transmission typically occurs via of aerosolized from contaminated or , or through wound contamination following in exposed settings. The pathogen exhibits global distribution, with notable case clusters reported in the United States (particularly during the peak era), (including the and ), and , often correlating with local equine populations and agricultural activities. This pattern parallels the observed in foals, highlighting shared environmental risk factors between animal and human hosts.

Pathogenesis and Virulence

Infection Mechanisms

Rhodococcus equi primarily infects the host through inhalation of contaminated aerosols or dust particles containing the bacterium, which are taken up by alveolar macrophages in the lungs. Upon entry, the bacteria are phagocytosed by these macrophages via receptor-mediated processes, including complement receptor 3 (CR3) and Fcγ receptors, without inducing significant oxidative burst in unprimed cells. Virulent strains evade immediate killing by arresting phagosome maturation at an early endosomal stage, preventing the acquisition of antimicrobial properties such as lysosomal enzymes and reactive oxygen species. Intracellular survival of R. equi relies on inhibition of phagosome-lysosome fusion and maintenance of a to mildly acidic phagosomal , with levels around 7.2 in infected macrophages, far above the acidic conditions ( <5.5) that would activate degradative mechanisms. This arrest allows the bacterium to replicate slowly within the modified over 24-72 hours, eventually leading to host cell rather than , as evidenced by membrane disruption and lack of activation. The virulence-associated protein VapA plays a critical role in this survival by neutralizing phagosomal acidification and supporting intramacrophage proliferation. Upon lysis, released R. equi disseminate locally, triggering an influx of neutrophils and formation of characteristic pyogranulomatous lesions in the lungs, which consist of central surrounded by macrophages and fibroblasts. elicits a pro-inflammatory response, including elevated TNF-α and IL-12 production from infected macrophages, which promotes formation but may contribute to tissue damage if unchecked. Susceptibility to R. equi infection is heightened in foals due to immature immune responses, particularly impaired IFN-γ production by T cells and natural killer cells, which fails to activate macrophages effectively for bacterial clearance. In humans, infections predominantly occur in immunocompromised individuals, such as those with exhibiting + T-cell counts below 200 cells/μL, where depleted adaptive immunity allows unchecked intracellular replication.

Key Virulence Factors

Rhodococcus equi possesses several molecular virulence determinants that facilitate its survival and proliferation within macrophages, in addition to plasmid-encoded factors. One prominent factor is the surface capsule, which exhibits antiphagocytic properties and may aid in to host cells. This extracellular structure, composed of repeating sugar units, has been identified as a potential contributor to by shielding the bacterium from and complement-mediated killing. However, experimental evidence from capsule-deficient mutants indicates that it is not essential for pathogenicity, as these strains retain full in models, suggesting the capsule primarily supports environmental persistence rather than direct host interaction. Iron acquisition systems are critical for R. equi to scavenge essential nutrients in iron-limited tissues. The bacterium produces the hydroxamate rhequichelin, which chelates ferric iron with high affinity, enabling uptake via specific transporters. Deletion of the rhequichelin biosynthesis gene rhbC results in attenuated in macrophages and reduced bacterial burdens in infected lungs, confirming its role in intracellular . Additionally, R. equi employs the iupABC for and iron acquisition, though mutants in this system show no significant defect, indicating redundant mechanisms. Enzyme production enables R. equi to counteract antimicrobial defenses, particularly the oxidative burst generated by macrophages. (KatA) is a key that decomposes ; katA mutants display heightened susceptibility to killing. These enzymes collectively promote evasion of the oxidative and acidic stresses encountered during . Cholesterol-dependent cytolysins, such as the secreted (ChoE), contribute to post-replicative cell lysis by oxidizing membrane , leading to formation and cell damage. Although ChoE is produced by both virulent and avirulent strains and choE mutants are not attenuated , it facilitates initial membrane disruption, allowing bacterial escape after intracellular multiplication. Recent studies highlight formation as an emerging trait, enabling R. equi to establish persistent communities on tissues and indwelling devices, thereby enhancing and tolerance. These factors are modulated in part by the , underscoring their coordinated role in . In , can often occur independently of the , unlike in foals where it is essential.

Genetic Elements of Virulence

Virulence Plasmid

The plasmid of Rhodococcus equi, designated pVAPA in equine-associated strains, is a large extrachromosomal critical for the bacterium's ability to cause in susceptible hosts. This typically measures 80–90 kb in size and is detected in more than 95% of isolates capable of inducing . Its conjugative properties facilitate broad-host-range transfer, allowing dissemination among bacterial populations in diverse environments. The plasmid's conserved backbone ensures genetic stability and propagation, comprising modules for replication (including rep genes), partitioning (par system), and that support its maintenance and intercellular spread. These elements are highly similar across plasmid variants, underscoring their role in the plasmid's evolutionary persistence. Loss of the plasmid renders strains avirulent, as it is indispensable for survival and replication within host macrophages, the primary site of infection. Horizontal transfer of the occurs efficiently in , the natural of R. equi, as evidenced by conjugative mechanisms and environmental dissemination studies. Three primary variants predominate: the equine type (pVAPA, associated with vapA), the porcine type (pVAPB, associated with vapB), and the /bovine type (pVAPN, associated with vapN), exhibiting over 90% sequence conservation in their backbones while adapting to host-specific . These variants integrate with chromosomal elements like the to enhance overall , though the itself remains the core determinant of infectivity.

Pathogenicity Island

The pathogenicity island (PAI) of Rhodococcus equi is a horizontally acquired genomic region approximately 20 kb in length, integrated into the backbone of the 80–90 kb virulence plasmid and characterized by high sequence variability due to recombination and selective pressures. This island is flanked by mobility-conferring elements, including resA-like resolvase and invA-like integrase genes near its variable region, facilitating its and host adaptation. Central to the PAI is the vap , encoding virulence-associated proteins (Vaps) that promote intracellular . The vapA produces a 17.4 kDa surface-exposed , the major determinant in equine-associated strains, which binds host membrane lipids such as to inhibit phagosome maturation and prevent fusion with lysosomes, allowing bacterial proliferation within macrophages. In porcine strains, the PAI harbors an expanded vap repertoire including vapBvapH, with vapB serving as the primary homolog to vapA and driving pig-specific pathogenicity through similar mechanisms. In strains, vapN plays an analogous role. Expression of vap genes is tightly regulated by the VirR-VirS system within the PAI: VirR, a LysR-type transcriptional activator, and VirS (encoded by orf8), an orphan OmpR/PhoB response regulator functioning in a sensor-independent manner but responsive to phagosomal cues, collectively induce vapA transcription under acidic pH (∼5.0) and 37–39°C conditions encountered during infection. A 2022 pan-genome analysis of 53 R. equi strains revealed that PAI acquisition and diversification correlate with host tropism, with clade-specific vap variants determining equine, porcine, ruminant, or human infectivity; a 2025 phylogenomic study of multi-host strains confirmed plasmid type distribution and zoonotic implications as of November 2025. Disruption of the PAI, particularly vapA deletion, abolishes in experimental models: avirulent mutants fail to multiply in murine macrophages or cause in foals, underscoring the island's indispensable role in .

Clinical Manifestations and

Disease Presentation

In foals, Rhodococcus equi infection typically manifests as suppurative , with clinical signs including fever, , , , and increased respiratory effort due to ventral consolidation and formation. Extrapulmonary involvement occurs in 50-74% of cases, featuring in sites such as the , joints, or lymph nodes. In humans, particularly immunocompromised individuals such as those with AIDS, R. equi causes subacute that often mimics , characterized by cavitation, lung abscesses, , fever, nonproductive , and dyspnea. Disseminated forms may include bacteremia, , and involvement of other organs like the or skin. A 2025 literature review of cases up to 2024 reported a mortality rate of 35% among HIV/AIDS patients with R. equi infection. Pathologically, R. equi infections produce pyogranulomas featuring central surrounded by layers of macrophages, neutrophils, and fibrous , leading to suppuration and destruction in affected lungs or other sites. The disease progression in both foals and humans involves an of 2-4 weeks following of contaminated dust or soil, potentially leading to complications such as and if untreated. Diagnostic , such as thoracic ultrasonography or , may reveal areas of and abscesses, aiding early recognition.

Diagnosis and Treatment

Diagnosis of Rhodococcus equi infection typically relies on laboratory confirmation through microbiological culture, molecular techniques, and imaging modalities, particularly in foals where pneumonia is the primary presentation and in humans where disseminated disease is common. Bacterial culture remains a cornerstone, with selective media such as NANAT agar facilitating the isolation of R. equi from clinical samples like transtracheal washes, bronchoalveolar lavage fluid, or abscess aspirates; this medium inhibits competing flora while promoting the growth of characteristic mucoid, salmon-pink colonies after 48-72 hours of incubation at 37°C. Polymerase chain reaction (PCR) targeting the vapA gene, which encodes a key virulence protein, provides rapid and sensitive detection of virulent strains in respiratory secretions, feces, or tissues, with quantitative real-time PCR offering utility for assessing bacterial load in serial samples from foals. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) enables accurate identification of isolates as R. equi with high confidence scores, often outperforming traditional biochemical methods in veterinary and human clinical laboratories. Imaging, including thoracic ultrasound for detecting pulmonary abscesses in foals or computed tomography (CT) for evaluating cavitary lesions in human patients, supports presumptive diagnosis by revealing characteristic pyogranulomatous consolidations, though it is not specific to R. equi. Serological tests and biomarkers have limited diagnostic value due to variable , particularly in early infection stages. Enzyme-linked immunosorbent assay () detecting antibodies against R. equi antigens, such as VapA, can indicate prior exposure in foals but often fails to distinguish active disease from subclinical colonization or maternal immunity, with studies showing poor performance in confirming . Histopathological examination of affected tissues reveals suppurative to pyogranulomatous with intracellular Gram-positive coccobacilli within macrophages, aiding in cases where is inconclusive, though acid-fast staining may be required to differentiate from mycobacteria. Treatment of R. equi infections emphasizes prolonged combination antimicrobial due to the bacterium's intracellular and tendency for formation, with regimens tailored to host species and site of infection. In foals with , the synergistic combination of a such as and rifampin is the standard, achieving high clinical cure rates through effective intracellular penetration and bactericidal activity, typically administered orally for the duration of . For infections, particularly in immunocompromised individuals, intravenous combined with imipenem or is recommended as first-line to address severe or extrapulmonary , with transition to oral agents like and rifampin once stable. Emerging multidrug resistance, including to erythromycin in up to 40% of isolates in some regions as of 2016, has been documented in veterinary settings and linked to international spread and practices like "screen and treat" protocols; this prompts susceptibility testing and alternative regimens like gamithromycin or in resistant cases. Treatment duration generally spans 4-8 weeks, extended to 3-6 months or longer for extrapulmonary or cavitary , with surgical drainage of essential for source control in both species when alone is insufficient. Therapeutic monitoring involves serial clinical assessment, imaging resolution, and PCR-based detection of vapA clearance from respiratory or fecal samples to guide and prevent .

Prevention and Recent Advances

Control Strategies

Effective control of Rhodococcus equi in foals relies heavily on farm management practices aimed at reducing environmental exposure to the bacterium, which thrives in and . Key strategies include dust control through regular watering of arenas and paddocks to minimize aerosolized particles, frequent manure removal to limit bacterial proliferation in paddocks and stalls, and of affected or high-risk foals to prevent within the herd. These measures have been shown to lower infection rates on endemic farms by reducing the airborne concentration of virulent R. equi. Additionally, administering hyperimmune transfusions to neonatal foals provides , decreasing the severity of in experimental challenges, with studies demonstrating reduced lesion scores and clinical signs in treated groups. Hygiene protocols further support prevention by maintaining clean environments and avoiding conditions that favor . Regular disinfection of stalls and equipment using appropriate agents disrupts bacterial reservoirs, while preventing in foaling areas reduces stress and transmission risk among foals. The American Association of Equine Practitioners (AAEP) guidelines emphasize , including the use of quantitative (qPCR) to detect virulent R. equi in dust and feces, enabling early intervention on high-risk farms. These practices, when implemented consistently, contribute to lower incidence rates without relying on broad-spectrum interventions. Antimicrobial stewardship is crucial for managing R. equi infections, particularly given the emergence of resistant strains that complicate treatment. Prophylactic antimicrobial use should be limited to high-risk foals identified through screening, such as thoracic ultrasonography, to avoid unnecessary exposure and preserve drug efficacy. Ongoing resistance surveillance on farms, including susceptibility testing of isolates, helps guide and informs broader efforts in equine practice. Zoonotic transmission of R. equi, though rare, poses risks to immunocompromised individuals and veterinary personnel handling infected foals. Prevention focuses on (PPE), such as gloves, masks, and gowns during procedures involving aerosols or bodily fluids, combined with rigorous hand hygiene using soap and water or alcohol-based sanitizers after contact. These measures, outlined in veterinary standard precautions, effectively mitigate occupational exposure in clinical settings. Challenges from multidrug-resistant strains underscore the need for integrated control to limit both equine and human health impacts.

Emerging Research

Recent genomic analyses have advanced the understanding of Rhodococcus equi diversity and . A 2022 pan-genome study of 53 strains from various sources identified a core of 3,690 genes and a total size of 11,481 genes, highlighting significant accessory variability that contributes to strain-specific traits. This analysis revealed variations in the (PAI) across virulence plasmids, including Type-A (equine-associated), Type-B (porcine-associated), and Type-N (bovine-associated) types, with sequence similarities among vap genes ranging from 56% to 76%, indicating host-specific and . Type-B plasmids were notably prevalent in isolates, linking exposure as a potential zoonotic for adaptation to new hosts. Genetic manipulation techniques have elucidated the role of key factors. Studies using ΔvapA strains have demonstrated that VapA is essential for intracellular survival in macrophages, with complemented strains showing restored growth in cellular models. Although CRISPR-Cas9 applications in R. equi remain emerging, related gene editing approaches in actinomycetes have informed development by targeting vap loci for . Vaccine research has progressed toward safer, more effective immunogens for foals. Live-attenuated strains, such as auxotrophs retaining the virulence plasmid, have shown promise in preclinical models, reducing bacterial loads in challenged animals by eliciting targeted immune responses without full . Recent trials with intramuscular mRNA vaccines encoding VapA demonstrated robust in neonatal foals, with titers persisting for weeks post-vaccination, though nebulized delivery was less immunogenic. Ongoing research explores mRNA platforms encoding VapA, with studies targeting regulators like VirR to modulate vap expression for improved efficacy. As of 2025, no licensed exists for R. equi, though 2025 studies on enteral with live bacteria have demonstrated reprogrammed innate immune responses in neonatal foals, offering new avenues for prevention. Antimicrobial resistance poses growing challenges, prompting novel therapeutic explorations. A 2022 CDC report documented the international spread of multidrug-resistant (MDR) R. equi clone 2287, originating from U.S. equine farms and detected in Europe, linked to macrolide-rifampin prophylaxis overuse. Phage therapy has emerged as a strategy against MDR strains, with the isolation of R. equi-specific bacteriophage ReT1 in 2025 showing lytic activity and potential for biofilm disruption in vitro, where R. equi forms persistent matrices reducing antibiotic efficacy. In human medicine, R. equi infections are rising beyond contexts. Recent reports indicate increasing R. equi infections in non- immunocompromised patients, such as those with malignancies or post-transplant, predominantly presenting as pulmonary with mortality rates of 20-30% despite . Innovative delivery systems, including liposomal gentamicin, have enhanced targeting in models, significantly reducing splenic R. equi burdens compared to free drug, offering a model for intracellular .

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