The number of pathogens that are required to infect a host, termed infective dose, varies dramatically across pathogen\nspecies. It has recently been predicted that infective dose will depend upon the mode of action of the molecules that\npathogens use to facilitate their infection. Specifically, pathogens which use locally acting molecules will require a lower\ninfective dose than pathogens that use distantly acting molecules. Furthermore, it has also been predicted that\npathogens with distantly acting immune modulators may be more virulent because they have a large number of cells in\nthe inoculums, which will cause more harm to host cells. We formally test these predictions for the first time using data\non 43 different human pathogens from a range of taxonomic groups with diverse life-histories. We found that pathogens\nusing local action do have lower infective doses, but are not less virulent than those using distant action. Instead, we\nfound that virulence was negatively correlated with infective dose, and higher in pathogens infecting wounded skin,\ncompared with those ingested or inhaled. More generally, our results show that broad-scale comparative analyses can\nexplain variation in parasite traits such as infective dose and virulence, whilst highlighting the importance of mechanistic\ndetails.
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