Interaction of virulent and non-virulent Rhodococcus equi human isolates with phagocytes, fibroblast- and epithelial-derived cells

Nordmann, P

doi:10.1016/0928-8244(94)90088-4

Cited by 4 publications

(4 citation statements)

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“…There have been reports that mentioned (20,25,38,62) or demonstrated (25,37) the presence of a cytotoxic effect on mammalian cells of some "virulent" R. equi versus a lack thereof in "avirulent" ones, but the correlation between possession of a virulence-associated plasmid and cytotoxic potential has not been described. We now present evidence that the cytotoxic potential is regulated by virulence-associated plasmids.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, R. equi is found frequently in macrophages in vivo (24), although it does not seem to enter pulmonary epithelial cells. It has been reported that R. equi interferes with the maturation of its phagosomes to phagolysosomes in primary foal alveolar macrophages (20,62), that some virulent R. equi bacteria are able to destroy host cells (20,37), and that virulent or avirulent R. equi induces similar levels and types of cytokines in infected murine macrophages (17). Still, almost nothing is known about the molecular mechanisms underlying the pathogenicity of R. equi.…”

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confidence: 99%

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Necrotic Death ofRhodococcus equi-Infected Macrophages Is Regulated by Virulence-Associated Plasmids

et al. 2004

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Rhodococcus equi is a gram-positive intracellular pathogen that can cause severe bronchopneumonia in foals and AIDS patients. It has been reported that advanced infection of foals is characterized by tissue necrosis, coinciding with the presence of degenerate bacteria-laden macrophages. Here, we report that the possession of the VapA-expressing plasmid, which has been previously correlated with a high level of virulence for foals and mice, strongly increases cytotoxicity of R. equi for murine macrophage-like (J774E) cells. Isolates containing different, VapB-expressing plasmids are less virulent and also have a lower cytotoxic potential. Isogenic strains lacking either plasmid are avirulent and have a very low cytotoxic potential. We show, using fluorescenceactivated cell sorter analysis (annexin V/7-amino-actinomycin D and sub-G 1 -analysis), Western blotting [poly-(ADP-ribose) polymerase processing analysis], and electron microscopy (macrophage and nucleus morphologies) that the deaths of murine macrophages are the result of necrotic rather than apoptotic events. We demonstrate that the bacteria must be alive in order to act cytotoxic. Therefore, one effect of the virulenceassociated plasmids during infection with R. equi is the promotion of necrotic damage to the host.Rhodococcus equi is a nocardioform gram-positive coccobacillus and an important foal pathogen producing severe pyogranulomatous pneumonia in very young horses (24, 38). Infection usually occurs via the respiratory tract. In addition to being a foal pathogen, R. equi can infect AIDS patients, and more than 100 cases in which patients showed symptoms and histopathology similar to those seen in infected foals and leading to death in ϳ50% of the individuals have been documented (8,29,59). Furthermore, a low number of cases that occurred in immunocompetent humans with an ϳ11% mortality rate have been reported (29). In addition to their own importance in human and veterinary medicine, these bacteria have a close phylogenetic relationship to mycobacteria and, hence, to such important pathogens as Mycobacterium tuberculosis (causing human tuberculosis) and Mycobacterium leprae (causing leprosy). Members of both genera, Mycobacterium and Rhodococcus, are largely soil inhabitants and possess complex wax-like cell walls (4) enriched in lipoarabinomannans (41), in mycolic acids, and in mycolic-acid derived compounds such as cord factor (trehalose dimycolate). Also, both M. tuberculosis and R. equi can produce caseous granulomas and cavitary pneumonia, demonstrating not only phylogenetic but also pathogenetic relatedness. Not surprisingly, some human infections with rhodococci have been mistaken for tuberculosis (55).Due to its capability to survive and multiply in murine and equine macrophages, R. equi has been classified as a facultative intracellular bacterium (25). Accordingly, R. equi is found frequently in macrophages in vivo (24), although it does not seem to enter pulmonary epithelial cells. It has been reported that R. equi interferes with the matur...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Necrotic Death ofRhodococcus equi-Infected Macrophages Is Regulated by Virulence-Associated Plasmids

et al. 2004

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“…In the case of infection with virulent strains, the disease outcome may be affected by the production of virulence factors which enhance the replicative capacity and prolong the survival of the organism within macrophages. In this respect, the 15to 17-kDa plasmid-encoded proteins, which are not recognized by antibody-mediated immunity, may mediate R. equi intramacrophage persistence, even if the involvement of other cell wall components, such as mycolic acids or toxic factors related to p-lactam resistance (16)(17)(18), cannot be excluded.…”

Section: Discussionmentioning

confidence: 99%

Rhodococcus equi Virulence-Associated Antigens and Specific Antibody Response in AIDS Patients Infected with R. equi

Mastroianni

Lichtner

Mengoni

et al. 1995

Clinical Microbiology and Infection

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OBJECTIVES: To analyze the expression of the 15- to 17-kDa plasmid-encoded antigens from Rhodococcus equi isolates of 7 AIDS patients and determine the immunologic response to these proteins in the patients' sera. METHODS: The expression of the virulence proteins in R. equi isolates and the specific antibody response were investigated by immunoblotting. Plasmid DNA was analyzed by agarose gel electrophoresis. RESULTS: The only patient infected with a strain carrying the virulence 85-kb plasmid and expressing the 15- to 17-kDa antigens developed a fatal pneumonia and did not produce specific antibodies to the virulence proteins. Of the 6 patients infected with R. equi strains lacking both proteins and plasmid, only 1 subject had a pulmonary disease with poor clinical outcome and exhibited a negligible humoral immune response to R. equi antigenic components, whereas the other patients who produced a remarkable antibody response developed either an asymptomatic infection (1 case) or pneumonia (4 cases) which completely cleared up. CONCLUSIONS: Our findings suggest that R. equi disease can be induced without the expression of the 15- to 17-kDa virulence-associated plasmid-encoded antigens in HIV-infected patients with very low CD4+ cell counts. Nevertheless, both the synthesis of the virulence proteins and a defective humoral immune response to R. equi may contribute to the severity of rhodococcal disease.

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“…However, little is known about the characteristics of R. equi strains isolated from humans. Cryptic plasmids of various sizes and fimbrial structures were detected frequently suggesting the antibiotic resistance (Nordmann et al 1994). The majority of clinical isolates of R. equi from imunossuppressed human patients did not carry virulence plasmids and were no virulent to mice, suggesting that the pathogenesis of R. equi infections in immunossupressed hosts may be different from that which occurs in foals (Meijer et al 2004).…”

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

Pathogenicity of Rhodococcus equi in mice, isolated from environment, human and horse clinical samples

Costa

Machado²,

Krewer

et al. 2006

Pesq. Vet. Bras.

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Rhodococcus equi is a facultative intracellular pathogen associated with bronchopneumonia, mesenteric lymphadenitis and enterocolitis in foals. Although R. equi is likely to be found in every horse-breeding farm, the clinical disease is unrecognized in most of them. Capsule components, equi factor, micolic acid and some products encoded by the large 85-90Kb plasmid were described as virulence factors. However, the pathogenesis of R. equi infections and the sensibility of foals are not completely understood. The aim of this study was evaluate the virulence of R. equi isolated from human, horses and environment for mices. Nine strains carrying the 85-90Kb plasmid isolated from foal clinical specimens, one from immunodeficient human patient and six plasmidless strains (four isolated from feces, one from pasture and one from immunodeficient human patient) were inoculated in cyclophosphamide immunossuppressed mice. The pathological changes and viability of R. equi cells in the liver of mice was verified after the 3rd, 6th an 10th day after inoculation for horse and environmental isolates and for R. equi isolates from human patients on the 1st, 3rd and 6th day. During the necropsy procedures, infiltrate of macrophages and pyogranulomatous lesions were detected after the sixth pos-inoculation day in the liver and spleen. In horse isolates, only plasmid positive strains were virulent, but in human isolates both strains (plasmid positive e plasmid negative) were virulent. Both groups of the immunossupressed mice inoculated with R. equi isolated from environment showed pathological changes. All R. equi strains were unable to kill non imunossuppressed mice.

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Interaction of virulent and non-virulent Rhodococcus equi human isolates with phagocytes, fibroblast- and epithelial-derived cells

Cited by 4 publications

References 17 publications

Necrotic Death ofRhodococcus equi-Infected Macrophages Is Regulated by Virulence-Associated Plasmids

Necrotic Death ofRhodococcus equi-Infected Macrophages Is Regulated by Virulence-Associated Plasmids

Rhodococcus equi Virulence-Associated Antigens and Specific Antibody Response in AIDS Patients Infected with R. equi

Pathogenicity of Rhodococcus equi in mice, isolated from environment, human and horse clinical samples

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