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Published on: January 13, 2016
In vivo and in vitro studies with an atypical, rhinotropic isolate of Cryptococcus neoformans
Abstract:
An atypical isolate of Cryptococcus neoformans was investigated because of its consistent and reproducible production of gross nasal pathology following i.v. injection in Swiss albino mice. Dose response to graded concentrations ranging from 1 X 10(2)-1 X 10(7) cells/mouse yielded an LD50 of 1.4 X 10(3) cells/mouse for the atypical rhinotropic strain H140 which was significantly less virulent (p less than 0.01) than our reference strain of Cryptococcus neoformans. There was no significant difference in mortality following the injection of in vitro vs. in vivo passed inoculum. As early as two weeks after inoculation, this strain produced gross nasal enlargement to approximately 2-3 X normal dimensions with granulomatous and ulcerated lesions. The LD60 resulted in the greatest percentage of nasal involvement (85%). C. neoformans was demonstrated by culture and histopathology in the noses, brains, lungs, livers and kidneys. A temperature selection was indicated by findings of a lower temperature minimum for subcultures isolated from the noses relative to those isolated from the brain, and by the fact that the most densely populated organs following intraperitoneal injection were the testes. This route of inoculation resulted in cutaneous nasal involvement in a manner analogous to that following i.v. injection. The atypical isolate was unable to assimilate trehalose or raffinose but otherwise was entirely consistent with identification as C. neoformans and produced characteristic CNS and general organ system disease in addition to the rhinotropic cutaneous manifestations. The model characterized here in normal mice may be of value in studies of fungal dermotropism.
Insights
An atypical Cryptococcus neoformans strain caused significant nasal pathology in mice, offering a new model for studying fungal dermotropism. This rhinotropic strain demonstrated unique temperature adaptations and organ tropism.
Area of Science:
- Mycology
- Infectious Diseases
- Immunology
Background:
- Cryptococcus neoformans is an opportunistic fungal pathogen.
- Nasal pathology is a known but less-studied manifestation of cryptococcosis.
- Atypical strains may exhibit unique pathogenic properties.
Purpose of the Study:
- To investigate an atypical Cryptococcus neoformans isolate with observed rhinotropic properties.
- To characterize the pathogenicity and host response to this strain in a murine model.
- To evaluate its potential as a model for studying fungal dermotropism.
Main Methods:
- Intravenous and intraperitoneal inoculation of Swiss albino mice with varying concentrations of the atypical strain H140.
- Assessment of mortality, gross nasal pathology, and organ dissemination via culture and histopathology.
- Biochemical characterization of the isolate, including assimilation tests.
Main Results:
- The atypical strain H140 exhibited significant rhinotropism, causing gross nasal enlargement and lesions in mice.
- An LD50 of 1.4 X 10^3 cells/mouse was determined, indicating lower virulence than a reference strain.
- Dissemination to the brain, lungs, liver, kidneys, and testes was observed, with evidence of temperature selection.
- The isolate was biochemically consistent with C. neoformans despite assimilation differences.
Conclusions:
- The characterized atypical Cryptococcus neoformans strain provides a valuable murine model for studying fungal dermotropism and nasal cryptococcosis.
- This model can aid in understanding the mechanisms of fungal dissemination and host-pathogen interactions.
- Further research into the unique properties of this rhinotropic strain is warranted.
