Abstract
The number of pathogens that are required to infect a host, termed infective dose, varies dramatically across pathogen species. It has recently been predicted that infective dose will depend upon the mode of action of the molecules that pathogens use to facilitate their infection. Specifically, pathogens which use locally acting molecules will require a lower infective dose than pathogens that use distantly acting molecules. Furthermore, it has also been predicted that pathogens with distantly acting immune modulators may be more virulent because they have a large number of cells in the inoculums, which will cause more harm to host cells. We formally test these predictions for the first time using data on 43 different human pathogens from a range of taxonomic groups with diverse life-histories. We found that pathogens using local action do have lower infective doses, but are not less virulent than those using distant action. Instead, we found that virulence was negatively correlated with infective dose, and higher in pathogens infecting wounded skin, compared with those ingested or inhaled. More generally, our results show that broad-scale comparative analyses can explain variation in parasite traits such as infective dose and virulence, whilst highlighting the importance of mechanistic details.
Highlights
There is huge variation across pathogen species in the number of cells required to successfully infect a host
If these molecules act locally, in the vicinity of the pathogenic cell, only small numbers of molecules may be required for successful growth and so infections can be established from small numbers of pathogenic cells
We found that mechanisms used by parasites to infect hosts are able to explain variation in two key pathogen traits: infective dose and virulence
Summary
There is huge variation across pathogen species in the number of cells required to successfully infect a host. Species such as Vibrio cholera and Staphylococcus aureus require 103–108 cells in order for an infection to develop [1,2,3] It is unclear why infective dose varies, with large differences occurring even between closely related pathogens [2,3]. If the pathogenic molecules diffuse and act at a distance, large numbers of molecules may be required for evading the host immune system In these cases greater numbers of pathogenic cells could be needed to establish an infection. Schmid-Hempel and Frank [2,3,9] further predicted that pathogens with distantly acting immune modulators will be more virulent, possibly because they would have a large numbers of cells in the inoculums, and higher parasite density would overwhelm the host immune system causing more harm to hosts. These factors could influence dose and virulence for a number of reasons, including their affect on: the extent to which virulence reduces pathogen transmission; the types of immune response they encounter; and the genetic diversity (or relatedness) of the pathogens either competing for or cooperating to exploit the host [2,3,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28]
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