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Mechanisms of Pathogenesis, Infective Dose and Virulence in Human Parasites


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.


Vyšlo v časopise: Mechanisms of Pathogenesis, Infective Dose and Virulence in Human Parasites. PLoS Pathog 8(2): e32767. doi:10.1371/journal.ppat.1002512
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002512

Souhrn

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.


Zdroje

1. SewellDL 1995 Laboratory-associated infections and biosafety. Clin Microbiol Rev 8 389 405

2. Schmid-HempelPFrankSA 2007 Pathogenesis, virulence, and infective dose. PLoS Pathog 3 1372 1373 doi:10.1371/journal.ppat.0030147

3. Schmid-HempelP 2011 Evolutionary Parasitology: The Integrated Study of Infections, Immunology, Ecology, and Genetics Oxford Oxford University Press

4. HarveyPHPagelMD 1991 Oxford series in ecology and evolution 1. The comparative method in evolutionary biology Oxford, UK Oxford University Press

5. FelsensteinJ 1985 Phylogenies and the comparative method. Am Nat 125 1 15

6. GrafenA 1989 The phylogenetic regression. Philos T Roy Soc B 326 119 157

7. CluttonbrockTHHarveyPH 1977 Primate ecology and social-organisation. J Zool 183 1 39

8. HadfieldJDNakagawaS 2010 General quantitative genetic methods for comparative biology: phylogenies, taxonomies and multi-trait models for continuous and categorical characters. J Evol Biol 23 494 508 doi:10.1111/j.1420-9101.2009.01915.x

9. FrankSASchmid-HempelP 2008 Mechanisms of pathogenesis and the evolution of parasite virulence. J Evol Biol 21 396 404 doi:10.1111/j.1420-9101.2007.01480.x

10. FrankSA 1996 Models of parasite virulence. Q Rev Biol 71 37 78

11. AlizonSHurfordAMideoNVan BaalenM 2009 Virulence evolution and the trade-off hypothesis: history, current state of affairs and the future. J Evol Biol 22 245 259 doi:10.1111/j.1420-9101.2008.01658.x

12. EwaldPW 1994 Evolution of Infectious Diseases Oxford, UK Oxford University Press

13. WildGGardnerAWestSA 2009 Adaptation and the evolution of parasite virulence in a connected world. Nature 459 983 986 doi:10.1038/nature08071

14. LionSBootsM 2010 Are parasites “prudent” in space? Ecol Lett 13 1245 1255 doi:10.1111/j.1461-0248.2010.01516.x

15. BootsMMealorM 2007 Local interactions select for lower pathogen infectivity. Science 315 1284 1286 doi:10.1126/science.1137126

16. BootsMSasakiA 1999 ‘Small worlds’ and the evolution of virulence: infection occurs locally and at a distance. Proc Biol Sci 266 1933 1938

17. BullJJ 1994 Perspective- Virulence. Evolution 48 1423 1437

18. EwaldPW 1991 Waterborne transmission and the evolution of virulence among gastrointestinal bacteria. Epidemiol Infect 106 83 119

19. HamiltonWD 1972 Altruism and related phenomena mainly in social insects. Annu Rev Ecol Syst 193 232

20. BullJJMolineuxIJRiceWR 1991 Selection of benevolence in a host-parasite system. Evolution 45 875 882

21. EwaldPW 1983 Host-parasite relations, vectors, and the evolution of disease severity. Annu Rev Ecol Syst 14 465 485

22. NowakMAMayRM 1994 Superinfection and the evolution of parasite virulence. P Roy Soc Lond B Biol 255 81 89

23. FrankSA 1994 Kin selection and virulence in the evolution of protocells and parasites. Proc Biol Sci 258 153 161

24. BrownSPHochbergMEGrenfellBT 2002 Does multiple infection select for raised virulence? Trends Microbiol 10 401 405

25. WestSABucklingA 2003 Cooperation, Virulence and Siderophore Production in Bacterial Parasites. Proc Biol Sci 270 37 44

26. GardnerAWestSABucklingA 2004 Bacteriocins, spite and virulence. Proc Biol Sci 271 1529 1535 doi:10.1098/rspb.2004.2756

27. EbertDBullJJ 2003 Challenging the trade-off model for the evolution of virulence: is virulence management feasible? Trends Microbiol 11 15 20

28. HerreEA 1993 Population-structure and the evolution of virulence in nematode parasites of fig wasps. Science 259 1442 1445

29. De RoodeJCFernandez de CastillejoCLFaitsTAlizonS 2011 Virulence evolution in response to anti-infection resistance: toxic food plants can select for virulent parasites of monarch butterflies. J Evol Biol 24 712 722 doi:10.1111/j.1420-9101.2010.02213.x

30. LevinSPimentelD 1981 Selection of intermediate rates of increase in parasite-host systems. Am Nat 117 308 315

31. BremermannHJPickeringJ 1983 A game-theoretical model of parasite virulence. J Theor Biol 100 411 426

32. vanBaalenMSabelisMW 1995 The dynamics of multiple infection and the evolution of virulence. Am Nat 146 881 910

33. de RoodeJCPansiniRCheesmanSJHelinskiMEHHuijbenS 2005 Virulence and competitive ability in genetically diverse malaria infections. Proc Natl Acad Sci USA 102 7624 7628 doi:10.1073/pnas.0500078102

34. EbertD 1998 Evolution - Experimental evolution of parasites. Science 282 1432 1435

35. KerrBNeuhauserCBohannanBJMDeanAM 2006 Local migration promotes competitive restraint in a host-pathogen ‘tragedy of the commons’. Nature 442 75 78 doi:10.1038/nature04864

36. RumbaughKPDiggleSPWattersCMRoss-GillespieAGriffinAS 2009 Quorum Sensing and the Social Evolution of Bacterial Virulence. Curr Biol 19 341 345 doi:10.1016/j.cub.2009.01.050

37. KohlerTBucklingAvan DeldenC 2009 Cooperation and virulence of clinical Pseudomonas aeruginosa populations. Proc Natl Acad Sci USA 106 6339 6344 doi:10.1073/pnas.0811741106

38. United States Food and Drug Administration 2003 The Bad Bug Book. Available: http://www.fda.gov/Food/FoodSafety/FoodborneIllness/FoodborneIllnessFoodbornePathogensNaturalToxins/BadBugBook/default.htm. Accessed 2 December 2009

39. Health Canada 2003 Pathogen safety data sheets. Available: http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/index-eng.php. Accessed 2 December 2009

40. Medscape. Infectious Disease Articles. Available: http://emedicine.medscape.com/infectious_diseases. Accessed 2 December 2009

41. Centers for Disease Control and Prevention. Alphabetical Index of Parasitic Diseases. Available: http://www.cdc.gov/parasites/az/index.html. Accessed 2 December 2009

42. World Health Organization. Publications and Fact sheets. Available: http://www.who.int/research/en/. Accessed 2 December 2009

43. ISI Web of knowledge database. Available: http://apps.isiknowledge.com. Accessed 2 December 2009

44. WilsonMMcNabRHendersonB 2002 Bacterial Disease Mechanisms: An introduction to cellular microbiology Cambridge Cambridge University Press

45. BrayM 2005 Pathogenesis of viral hemorrhagic fever. Curr Opin Immunol 17 399 403 doi:10.1016/j.coi.2005.05.001

46. WooldridgeK 2009 Bacterial Secreted Proteins: Secretory Mechanisms and Role in Pathogenesis Caister Academic Press

47. KrauseG Working group on prioritisation at the Robert Koch Institute 2008 How can infectious diseases be prioritized in public health? A standardized prioritization scheme for discussion. Embo Rep 9 S22 S27 doi:10.1038/embor.2008.76

48. SayersEWBarrettTBensonDABryantSHCaneseK 2009 Database resources of the National Center for Biotechnology Information (vol 37, pg D5, 2008). Nucleic Acids Res 37 3124 3124 doi:10.1093/nar/gkp382

49. CrawleyMJ 2002 Statistical Computing: An Introduction to Data Analysis using S-Plus West Sussex Wiley

50. KenwardMGRogerJH 1997 Small Sample Inference for Fixed Effects from Restricted Maximum Likelihood. Biometrics 53 983 997

51. LittellRCMillikenGAStroupWWWolfingerRDSchabenbergerO 2006 SAS for Mixed Models SAS Publishing

52. BolkerBMBrooksMEClarkCJGeangeSWPoulsenJR 2009 Generalized linear mixed models: a practical guide for ecology and evolution. Trends Ecol Evol 24 127 135 doi:10.1016/j.tree.2008.10.008

53. SelfSGLiangKY 1987 Asymptotic properties of maximum likelihood estimators and likelihood ratio tests under non-standard conditions. J Am Stat Assoc 82 605 610

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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