W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
PLoS Pathog. 2022 Jun 13;18(6):e1010484. doi: 10.1371/journal.ppat.1010484. eCollection 2022 Jun.
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.
致病性潜力（PP）是对个体微生物、病毒或寄生虫在宿主中引起疾病的能力的数学描述，给定变量包括接种量、疾病迹象、死亡率，在某些情况下，还包括宿主的中位存活时间。我们使用蜡螟（Galleria mellonella）中的两种致病性真菌，以死亡率为相关结果，研究了致病性潜力（PP）与感染接种量（I）之间的关系。我们对新型隐球菌感染的分析显示，PP 与 I 之间呈负指数关系。将 I 的对数与在中位宿主存活时间（T）上出现疾病迹象或症状的动物比例（Fs）作图，显示出线性关系，斜率因所研究的不同真菌而异，而截距对应于不产生任何疾病迹象的接种量。I 与 Fs/T 的斜率提供了衡量每种微生物物种致病性的指标，我们称之为致病性常数或 kPath。kPath 提供了一个新的参数，可用于定量比较给定宿主中微生物物种的相对毒力和致病性。此外，我们还研究了来自现有文献中发现的 PP 和 Fs/T 值。总体而言，Fs/T 与 PP 与接种量之间的关系因微生物物种而异，对零疾病迹象的外推允许计算微生物的最低致病性接种量（LPI）。微生物倾向于分为两类：一类是 PP 与 Fs/T 与 I 之间呈正线性关系，另一类是 PP 与 I 之间呈负指数关系，而 Fs/T 与 I 之间呈正对数关系。具有线性关系的微生物往往是细菌，而基于指数的关系则往往是真菌或更高阶的真核生物。致病性微生物的 PP 与 I 和 Fs/T 与 I 之间关系的类型和符号的差异表明，宿主-微生物相互作用导致疾病存在根本差异。
