On the relationship between Pathogenic Potential and Infective Inoculum

Abstract

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.

Visible‐Light‐Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload

“…[ 48 ] G. mellonella does not have adaptive immunity, but its innate immune system has similarities to that of vertebrates in terms of function and anatomy. [ 49 ] Importantly, pathogenicity in mice and G. mellonella models of infections is correlated, [ 48 , 50 ] suggesting that findings from studies with G. mellonella are translatable to vertebrates.…”

Amoeba predation ofCryptococcus: A quantitative and population genomic evaluation of the Accidental Pathogen hypothesis

“…A caveat that applies to our study as well as all prior investigations of the accidental pathogen hypothesis, are the challenges inherent to comparing virulence between Cryptococcus strains. Our analysis does not account for potentially important effects such as host genotype or experimental parameters such as the level of infective inoculum [66]. A second limitation comes from the use of a single species and strain of Acanthamoeba to assess resistance to amoeba.…”

Amoeba predation of Cryptococcus: A quantitative and population genomic evaluation of the accidental pathogen hypothesis

“…A caveat that applies to our study as well as all prior investigations of the accidental pathogen hypothesis, are the challenges inherent to comparing virulence between Cryptococcus strains. Our analysis does not account for potentially important effects such as host genotype or experimental parameters such as the level of infective inoculum [76]. A second limitation comes from the use of a single species and strain of Acanthamoeba to assess resistance to amoeba.…”