Serial Passage of Cryptococcus neoformans in Galleria mellonella Results in Increased Capsule and Intracellular Replication in Hemocytes, but Not Increased Resistance to Hydrogen Peroxide

Ali, Muhammad Fariz; Tansie, Stephen M.; Shahan, John R.; Seipelt-Thiemann, Rebecca L.; McClelland, Erin E.

doi:10.3390/pathogens9090732

Cited by 9 publications

(10 citation statements)

References 41 publications

(51 reference statements)

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“…The general dose-independent effect on survival could be the result of the slow and irregular growth of the microbe [11][12][13], or a damaging immune response that kills the host in response to few or many microbes (Table 1). In this regard, P. lutzii, P. brasiliensis, and H. capsulatum are both slow growing fungi with doubling rates in media ranging from 13 to 21 hours [11][12][13], compared with the ~2 hour doubling time of C. neoformans in culture [14] and ~5 hours in vivo during infection of G. mellonella hosts [15]. Associations between P. brasiliensis growth rate and virulence have been previously indicated [16].…”

Section: Fungal Pp Pp T Fs/t and K Path In G Mellonellamentioning

confidence: 99%

On the relationship between Pathogenic Potential and Infective Inoculum

Smith

Casadevall

2022

PLoS Pathog

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Pathogenic Potential (PP) is a mathematical description of an individual microbe, virus, or parasite’s ability to cause disease in a host, given the variables of inoculum, signs of disease, mortality, and in some instances, median survival time of the host. We investigated the relationship between pathogenic potential (PP) and infective inoculum (I) using two pathogenic fungi in the wax moth Galleria mellonella with mortality as the relevant outcome. Our analysis for C. neoformans infection revealed negative exponential relationship between PP and I. Plotting the log(I) versus the Fraction of animals with signs or symptoms (Fs) over median host survival time (T) revealed a linear relationship, with a slope that varied between the different fungi studied and a y-intercept corresponding to the inoculum that produced no signs of disease. The I vs Fs/T slope provided a measure of the pathogenicity of each microbial species, which we call the pathogenicity constant or kPath. The kPath provides a new parameter to quantitatively compare the relative virulence and pathogenicity of microbial species for a given host. In addition, we investigated the PP and Fs/T from values found in preexisting literature. Overall, the relationship between Fs/T and PP versus inoculum varied among microbial species and extrapolation to zero signs of disease allowed the calculation of the lowest pathogenic inoculum (LPI) of a microbe. Microbes tended to fall into two groups: those with positive linear relationships between PP and Fs/T vs I, and those that had a negative exponential PP vs I relationship with a positive logarithmic Fs/T vs I relationship. The microbes with linear relationships tended to be bacteria, whereas the exponential-based relationships tended to be fungi or higher order eukaryotes. Differences in the type and sign of the PP vs I and Fs/T vs I relationships for pathogenic microbes suggest fundamental differences in host-microbe interactions leading to disease.

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Section: Fungal Pp Pp T Fs/t and K Path In G Mellonellamentioning

confidence: 99%

On the relationship between Pathogenic Potential and Infective Inoculum

Smith

Casadevall

2022

PLoS Pathog

View full text Add to dashboard Cite

show abstract

“…The general dose-independent effect on survival could be the result of the slow and irregular growth of the microbe (11–13), or a damaging immune response that kills the host in response to few or many microbes (Table 1). In this regard, P. lutzii, P. brasiliensis , and H. capsulatum are both slow growing fungi with doubling rates in media ranging from 13 to 21 hours (11–13), compared with the ∼2 hour doubling time of C. neoformans in culture (14) and ∼5 hours in vivo during infection of G. mellonella hosts (15).…”

Section: Resultsmentioning

confidence: 99%

On the relationship between Pathogenic Potential and Infective Inoculum

Smith

Casadevall

2022

Preprint

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Pathogenic Potential (PP) is a mathematical description of an individual microbe, virus, or parasite’s ability to cause disease in a host, given the variables of inoculum, symptomology, mortality, and in some instances, median survival time of the host. We investigated the relationship between pathogenic potential (PP) and infective inoculum (I) using two pathogenic fungi in the wax moth Galleria mellonella with mortality as the relevant outcome. Our analysis for C. neoformans infection revealed negative exponential relationship between PP and I. Plotting the log(I) versus the Fraction symptomatic (Fs) over median host survival time (T) revealed a linear relationship, with a slope that varied between the different fungi studied and a y-intercept corresponding to the inoculum that produced no symptoms. The I vs Fs/T slope provided a measure of the pathogenicity of each microbial species, which we call the pathogenicity constant or kPath. The kPath provides a new parameter to quantitatively compare the relative virulence and pathogenicity of microbial species for a given host. In addition, we investigated the PP and Fs/T from values found in preexisting literature. Overall, the relationship between Fs/T and PP versus inoculum varied among microbial species and extrapolation to zero symptoms allowed the calculation of the lowest pathogenic inoculum (LPI) of a microbe. Microbes tended to fall into two groups: those with positive linear relationships between PP and Fs/T vs I, and those that had a negative exponential PP vs I relationship with a positive logarithmic Fs/T vs I relationship. The microbes with linear relationships tended to be bacteria, whereas the exponential-based relationships tended to be fungi or higher order eukaryotes. Differences in the type and sign of the PP vs I and Fs/T vs I relationships for pathogenic microbes suggest fundamental differences in host-microbe interactions leading to disease.

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“…The travel of this pathogen via translocation of wildlife has also been described [ 107 ]. The fact that the disease can emerge long after the actual seeding and that a potential increase in the virulence is proposed is a strong argument for monitoring spontaneous cryptococcosis in the wildlife [ 106 , 108 ]. The surveillance of animal cases may flag areas of a higher risk for environmental transmission to humans and other animals as well as the emergence of new areas [ 109 ].…”

Section: Discussionmentioning

confidence: 99%

Cryptococcus in Wildlife and Free-Living Mammals

Danesi

Falcaro

Miranda

et al. 2021

JoF

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Cryptococcosis is typically a sporadic disease that affects a broad range of animal species globally. Disease is a consequence of infection with members of the Cryptococcus neoformans or Cryptococcus gattii species complexes. Although cryptococcosis in many domestic animals has been relatively well-characterized, free-living wildlife animal species are often neglected in the literature outside of occasional case reports. This review summarizes the clinical presentation, pathological findings and potential underlying causes of cryptococcosis in various other animals, including terrestrial wildlife species and marine mammals. The evaluation of the available literature supports the hypothesis that anatomy (particularly of the respiratory tract), behavior and environmental exposures of animals play vital roles in the outcome of host–pathogen–environment interactions resulting in different clinical scenarios. Key examples range from koalas, which exhibit primarily C. gattii species complex disease presumably due to their behavior and environmental exposure to eucalypts, to cetaceans, which show predominantly pulmonary lesions due to their unique respiratory anatomy. Understanding the factors at play in each clinical scenario is a powerful investigative tool, as wildlife species may act as disease sentinels.

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Serial Passage of Cryptococcus neoformans in Galleria mellonella Results in Increased Capsule and Intracellular Replication in Hemocytes, but Not Increased Resistance to Hydrogen Peroxide

Cited by 9 publications

References 41 publications

On the relationship between Pathogenic Potential and Infective Inoculum

On the relationship between Pathogenic Potential and Infective Inoculum

On the relationship between Pathogenic Potential and Infective Inoculum

Cryptococcus in Wildlife and Free-Living Mammals

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