Pathogenicity ( retronymes portmanteau word from Greek πάθος pathos "suffering, disease" and γένεσις genesis "generation, born". See -genese ) is the fundamental ability of infectious agents ( bacteria , parasites , viruses , prions , toxins ), in certain organisms diseases to evoke. The adjective to is pathogenic (disease-causing potentially sickening), the opposite is non-pathogenic (non-disease-causing). Pathogens also with the noun (the) pathogen called. The extent of the pathogenicity (ability of the pathogen to multiply and the intensity of the toxin formation) is referred to as virulence , without a uniform measure being defined for it.
Pathogenicity is characterized by the toxicity and aggressiveness of a pathogen. The aggressiveness consists of the penetration, whereabouts and multiplication of the pathogen. For example, Clostridium tetani or Corynebacterium diphtheriae are not very aggressive, but very toxic, while Streptococcus pneumoniae is only slightly toxic. Pathogens are divided into four risk groups according to their hazard potential for humans . The work with them takes place in the corresponding biological protection level (English Biosafety Level ), with BSL-1 for activities with non-pathogenic up to BSL-4 for activities with highly pathogenic pathogens.
In a narrower sense, pathogenicity describes the ability of a pathogen (a parasitic organism such as bacteria , fungi , protozoa or parasites ) or parasitic molecules ( viruses , viroids , transposons , prions ) to damage a particular host through its acquisition of resources. Its opposite is apathogenicity , i. H. such an organism or substance does no harm to the host, it is apathogenic for the host . Pathogenicity is primarily a property of the pathogen, but only arises in contact with a host. Pathogenicity is increased by weakened hosts, e.g. B. when infected with Pneumocystis carinii or Cryptosporidium in patients with immunosuppression , intensified.
Various measures of pathogenicity can be determined experimentally, for example the minimum infectious dose ( i.e. the minimum dose at which a host becomes ill), the lethal dose (the dose that leads to certain death), the lethality at a certain dose of a pathogen ( i.e. the percentage of sick people who die at a certain dose), as well as the epidemiologically determined contagion index (how contagious a pathogen is) and the pathogenicity index (how many symptoms and to what degree the pathogen produces).
Other occasionally occurring properties are transmission (but not with Cryptococcus neoformans or some zoonoses ), adhesion , immune reactions of the host's own immune system , immunological escape mutants , mechanisms for immune evasion , a pathogenicity caused by the immune reaction (immunopathogenesis, e.g. the destruction of the lymph nodes in HIV , Arthus reactions with streptococcal infections or Tyrosis in tuberculosis ) and also changes in behavior of the host (eg. B. Yersinia pestis in fleas, Toxoplasma gondii in rats, the rabies virus in various mammals, the small liver fluke in ants or Polydnaviren at wasps prey). The property to kill (see mortality and mortality ) is given not all pathogens, some examples of which are human papillomavirus , herpes virus , adeno-associated virus , or rhinovirus .
The virulence of bacteria depends, among other things, on the existence of toxin proteins, which can also be part of a toxin-antitoxin pair. An association of virulence with an entire bacterial species only makes sense if there are no strains without virulence.
One observation in the pathogenesis in natural hosts is that pathogens adapted to the host usually do not harm it very much because they need it for their own development and the immune system is activated by cell damage and apoptosis , which in turn has a lowering effect on the virus concentration. Avoiding an immune reaction facilitates replication and transmission (synonymous with transmission ) to other hosts. For example, herpes simplex viruses reach infection rates (synonymous with contamination ) of over 90% of the German population with less pronounced symptoms. The simian immunodeficiency virus does not produce AIDS in its natural hosts , unlike HIV in humans. In contrast, infections with the Ebola virus in humans, but not in their natural hosts, are occasionally self- extinguishing due to their high virulence before efficient transmission takes place, since the host is severely weakened and soon dies, consequently its range of motion and thus its spread the virus is limited. A severe course of infection with high mortality (see lethality and mortality ) is usually an indication that the causative pathogen has not yet adapted to the organism in question as its reservoir host. However, the transition from pathogens with a high level of replication (and damage caused) to a permanent infection rate ( Infect and persist , avoiding damage) is fluid. In other words, adapted infectious objects tend to persist and a regulated rate of reproduction, while less adapted pathogens tend to lead to premature termination of the chain of infection . Among other things, bacteria use quorum sensing for this . Exceptions are e.g. B. H5N1 viruses in birds, Yersinia pestis and human smallpox viruses , which despite their prolonged occurrence claim comparatively high numbers of victims. Evolution also occurs in the host in response to a pathogen. This evolution is described in the gene-for-gene hypothesis . However, the adaptation usually takes place on the part of the host, since the pathogens compete with their conspecifics for resources and a less reproductive pathogen would perish more quickly. Therefore, a reduction in pathogenicity in pathogens occurs primarily in connection with an increased rate of reproduction.
The adaptation of the host to the pathogen is referred to as host restriction or host resistance . Known antiviral and antibacterial mechanisms in humans include e.g. B. the myxovirus resistance factor Mx1 , the PAMP receptors , the dsRNA-activated inhibitor of translation DAI, the melanoma differentiation antigen 5 ( MDA-5 ), the oligoadenylate synthase OAS1 , the Langerin , the tetherin , the SAM domain and HD domain 1 protein ( SAMHD1 ), the RIG-I , the APOBEC3 , the TRIM5alpha , the protein kinase R and the RNA interference . In addition, there is the immune response . Without pathogens, the evolution of the immune system would not be necessary. Plants have developed other mechanisms to defend themselves against pathogens.
In the case of vertical infection , according to the continuum hypothesis, a decrease in virulence is assumed when the proportion of vertical infection increases (i.e. from parent to offspring).
The trade-off hypothesis assumes that virulence is an unavoidable consequence of transmission. In the malaria pathogen Plasmodium sp. a decrease in transmission with increased virulence was observed.
The short-sighted evolution hypothesis describes virulence as an unavoidable consequence of mutation and selection of a pathogen when adapting to its direct host, without reference to other and later possible hosts. Meningococci , poliovirus and HIV are cited as examples .
The coincidental evolution hypothesis assumes that virulence is independent of transmission, i. H. the virulence arises for other reasons and is only a side effect. Examples are the toxin- forming soil bacteria Clostridium botulinum (forms the botulinum toxin ) and Clostridium tetani (forms the tetanus toxin ), to which the toxin does not provide any advantage in their normal habitat.
Classification according to host range
The specification of the pathogenicity can be described by the type of host: pathogens affecting humans are referred to as human pathogens , those affecting animals as zoopathogenic (animal pathogen), those affecting plants as phytopathogenic (plant pathogen). Depending on the ability to actually trigger a disease in individual cases , a distinction is made between facultative pathogenicity (not always pathogenic or only under certain circumstances) and obligate pathogenicity (always pathogenic). The origin of a pathogen can be outside the host (exopathogenic, most pathogens) or originate in the host itself (endopathogenic, e.g. some prions).
The term psychopathogenicity is used less often in connection with controversial content and dogmas of various religions and ideologies. In analogy to pathogenicity, the term here describes the property of such content to have a “damaging” effect on the mind.
Classification according to taxonomy
The group of inanimate pathogens includes prions , transposons , retroelements , viroids and viruses . Living pathogens occur as unicellular (bacteria, fungi and protists) and multicellular ( parasites ).
The idea of the pathogenicity of microorganisms arose at the end of the 18th century . At that time, the dispute between contagionists , i.e. representatives of the idea of infectious diseases, and anti-contagionists was decided in favor of the former. The transferability of diseases through pathogenic organisms has not been scientifically questioned since the end of the 19th century.
- Robert G. Webster , A. Granoff (Eds.): Encyclopedia of Virology. Academic Press Ltd., San Diego 1996, ISBN 978-0-12-374410-4 .
- JH Strauss, EG Strauss: Viruses and human disease. Academic Press Ltd., San Diego 2002, ISBN 0-12-673050-4 .
- DM Knipe, Peter M. Howley , DE Griffin (Eds.): Fields Virology. 5th edition. Lippincott Williams & Wilkins, Philadelphia 2007, ISBN 978-0-7817-6060-7 .
- ^ B. Alberts, A. Johnson, J. Lewis: Introduction to Pathogens . In: Molecular Biology of the Cell , 4th. Edition, Garland Science, 2002, p. 1 (Retrieved April 26, 2016).
- ↑ LA Pirofski, A. Casadevall: Q and A What is a pathogen? A question that begins the point. In: BMC Biol. 10: 6 (2012). PMID 22293325 . PMC 3269390 (free full text)
- ↑ a b A. Casadevall, LA Pirofski: Host ‐ Pathogen Interactions: The Attributes of Virulence. In: J Infect Dis . 184 (3) 337-344 (2001). PMID 11443560 . PDF
- ^ FS Stewart: Bacteria in Health and Disease. In: Bacteriology and immunology for students of medicine . Williams and Wilkins, Baltimore 1968, pp. 72-91.
- ^ A b R. Poulin, C. Combes: The concept of virulence: interpretations and implications. In: Parasitol Today 15: 474-5 (1999). PMID 10557145 .
- ↑ Kalliopi Georgiades, Didier Raoult: Comparative Genomics Evidence That Only Protein Toxins are Tagging Bad Bugs. In: Frontiers in Cellular and Infection Microbiology. 1, 2011, S., doi : 10.3389 / fcimb.2011.00007
- ^ F. von Rheinbaben, MH Wolff: Handbook of virus-effective disinfection. Springer-Verlag, 2013, ISBN 9783642563942 , p. 7.
- ↑ a b V. J. Torres, DL Stauff et al .: A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence. In: Cell Host Microbe. Vol. 1, No. 2, 2007, pp. 109-19, PMID 18005689 . PMC 2083280 (free full text)
- ↑ G. Silvestri: Naturally SIV-infected sooty mabeys: are we closer to understanding why they do not develop AIDS? In: J Med Primatol. (2005) 34 (5-6): 243-52. PMID 16128919 .
- ↑ MJ Pantin-Jackwood, DE Swayne: Pathogenesis and pathobiology of avian influenza virus infection in birds. In: Rev Sci Tech. (2009) 28 (1): 113-36. PMID 19618622 .
- ↑ a b P. N. Jimenez, G. Koch, JA Thompson, KB Xavier, RH Cool, WJ Quax: The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. In: Microbiol Mol Biol Rev. (2012), Vol. 76, No. 1, pp. 46-65. doi : 10.1128 / MMBR.05007-11 . PMID 22390972 ; PMC 3294424 (free full text).
- ↑ KD Mir, MA Gasper, V. Sundaravaradan, DL Sodora: SIV infection in natural hosts: resolution of immune activation during the acute-to-chronic transition phase. In: Microbes Infect. (2011), Vol. 13 (1), pp. 14-24. PMID 20951225 ; PMC 3022004 (free full text).
- ^ PX Kover, K. Clay: Trade-off between virulence and vertical transmission and the maintenance of a virulent plant pathogen. In: The American naturalist. Volume 152, Number 2, August 1998, pp. 165-175, doi : 10.1086 / 286159 , PMID 18811383 .
- ^ S. Alizon, A. Hurford, N. Mideo, M. Van Baalen: Virulence evolution and the trade-off hypothesis: history, current state of affairs and the future. In: Journal of evolutionary biology. Volume 22, Number 2, February 2009, pp. 245-259, doi : 10.1111 / j.1420-9101.2008.01658.x , PMID 19196383 .
- ↑ MJ Mackinnon, AF Read: Virulence in malaria: an evolutionary viewpoint. In: Philosophical transactions of the Royal Society of London. Series B, Biological sciences. Volume 359, number 1446, June 2004, pp. 965-986, doi : 10.1098 / rstb.2003.1414 , PMID 15306410 , PMC 1693375 (free full text).
- ^ RE Paul, T. Lafond, CD Müller-Graf, S. Nithiuthai, PT Brey, JC Koella: Experimental evaluation of the relationship between lethal or non-lethal virulence and transmission success in malaria parasite infections. In: BMC Evolutionary Biology. Volume 4, September 2004, p. 30, doi : 10.1186 / 1471-2148-4-30 , PMID 15355551 , PMC 520815 (free full text).
- ↑ a b B. R. Levin: The evolution and maintenance of virulence in microparasites. In: Emerging infectious diseases. Volume 2, number 2, 1996 Apr-Jun, pp. 93-102, doi : 10.3201 / eid0202.960203 , PMID 8903208 , PMC 2639826 (free full text).
- ^ BR Levin, JJ Bull: Short-sighted evolution and the virulence of pathogenic microorganisms. In: Trends in microbiology. Volume 2, Number 3, March 1994, pp. 76-81, PMID 8156275 .
- ^ SJ Gould, RC Lewontin: The spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist program. In: Proceedings of the Royal Society of London. Series B, Biological sciences. Volume 205, Number 1161, September 1979, pp. 581-598, PMID 42062 .