Dataset Information

Mechanisms of pathogenesis, infective dose and virulence in human parasites.

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.

SUBMITTER: Leggett HC

PROVIDER: S-EPMC3280976 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundThe most severe form of human malaria is caused by the protozoan parasite Plasmodium falciparum. This unicellular organism is a member of a subgenus of Plasmodium called the Laverania that infects apes, with P. falciparum being the only member that infects humans. The exceptional virulence of this species to humans can be largely attributed to a family of variant surface antigens placed by the parasites onto the surface of infected red blood cells that mediate adherence to the vascular endothelium. These proteins are encoded by a large, multicopy gene family called var, with each var gene encoding a different form of the protein. By changing which var gene is expressed, parasites avoid immune recognition, a process called antigenic variation that underlies the chronic nature of malaria infections.ResultsHere we show that the common ancestor of the branch of the Laverania lineage that includes the human parasite underwent a remarkable change in the organization and structure of elements linked to the complex transcriptional regulation displayed by the var gene family. Unlike the other members of the Laverania, the clade that gave rise to P. falciparum evolved distinct subsets of var genes distinguishable by different upstream transcriptional regulatory regions that have been associated with different expression profiles and virulence properties. In addition, two uniquely conserved var genes that have been proposed to play a role in coordinating transcriptional switching similarly arose uniquely within this clade. We hypothesize that these changes originated at a time of dramatic climatic change on the African continent that is predicted to have led to significant changes in transmission dynamics, thus selecting for patterns of antigenic variation that enabled lengthier, more chronic infections.ConclusionsThese observations suggest that changes in transmission dynamics selected for significant alterations in the transcriptional regulatory mechanisms that mediate antigenic variation in the parasite lineage that includes P. falciparum. These changes likely underlie the chronic nature of these infections as well as their exceptional virulence.

Dataset Information

Mechanisms of pathogenesis, infective dose and virulence in human parasites.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets