A novel murine model of disseminated trichosporonosis

Abstract

Serious infections caused by Trichosporon beigelii have been noted with increasing frequency in immunocompromised patients. Progress in understanding the pathogenesis of this emerging infection has been limited by the lack of an animal model. We developed a CF1 mouse intravenous inoculation model of disseminated trichosporonosis to evaluate the pathogenicity of T. beigelii in transiently immunosuppressed mice. Four inocula (1 X 106, 1 X 107, 2 x 107, and 4 x 107 CFU per animal) of one clinical strain of T. beigelii 3001 were tested. Mice in groups of 10 were each injected with a single intravenous dose of one inoculum. Mortality correlated with inoculum size, as survival time was significantly shorter in mice injected with 4 x 107 or 2 x 107 CFU than in mice that received 1 x 107 or 1 x 106 CFU (P < 0.01). Necrotizing abscesses with conidial and hyphal elements and neutrophil and macrophage infiltration were observed in all major organs examined. Resistance to infection was markedly lowered by immunosuppression with either cyclophosphamide or cortisone acetate, with a significantly shorter survival time and a greater fungal burden per organ in immunosuppressed animals than in normal animals (P < 0.01). Nine additional strains were inoculated intravenously with around 5 x 106 CFU. Injection of each of these strains caused 100%/O mortality, in a pattern similar to that observed with strain 3001.

Virulence characteristics of oral treponemes in a murine model

“…DEX treatment of mice had a negligible effect on abscess induction by any of the oral treponemes. A report by Gokaslan and Anaissie (13) demonstrated that cyclophosphamide treatment of mice acutely decreased neutrophil numbers, which significantly increased the virulence of Trichosporon beigelii. Thus, we examined the effect of this immunosuppressive agent in altering the susceptibility of the host to infection with T. pectinovorum P2 as a representative of the oral treponemes (Fig.…”

“…The murine abscess model as originally described by Kastelein et al (19) and modified by Kesavalu et al (20)(21)(22)(23) was used to examine the virulence of the oral treponeme strains ( Table 1). Five to 10 mice per group were used, including the following: (i) normal mice, i.e., untreated mice challenged with viable treponemes (single injection per mouse); (ii) DEX mice, i.e., mice pretreated with dexamethasone (DEX, 40 g per animal; Fujisawa USA, Inc., Deerfield, Ill.) for 3 days prior to challenge infection, which has been shown to decrease neutrophil infiltration into sites of inflammatory lesions (45); and (iii) neutropenic mice, i.e., mice pretreated with cyclophosphamide (CYCL; Sigma) at a dose of 150 mg/kg of body weight 24 h before treponeme infection (13). For determination of virulence and abscess-forming capability, appropriate dilutions of bacteria in broth were made under anaerobic conditions.…”

Effects of granulocyte and granulocyte-macrophage colony-stimulating factors in a neutropenic murine model of trichosporonosis

“…Resistance to T. asahii infection was markedly lowered by CY. CY, a common agent used to obtain immunocompromised animal models (2,12,13,19,37,45), causes transient decreases in PMN, monocyte, and lymphocyte counts. The neutropenia in our CY model persisted for 6 days; however, most of the animals died after that period.…”

“…The neutropenia in our CY model persisted for 6 days; however, most of the animals died after that period. Thus, the initial host defense phenomena might be irretrievable, and reactions associated with migration of inflammatory cells upon recovery to sites of infection could have contributed to deterioration leading to death (13).…”

“…Experimental models of disseminated trichosporonosis have contributed to clarification of the mechanisms of host defense against the pathogen and provided a means for testing newer treatments (2,11,13,19,51). The investigation into Trichosporon itself also has contributed to development of better diagnostic procedures and therapies (17,24,29,47).…”