Inbiology, apathogen (Greek:πάθος,pathos "suffering", "passion" and-γενής,-genēs "producer of"), in the oldest and broadest sense, is anyorganism or agent that can producedisease. A pathogen may also be referred to as aninfectious agent, or simply agerm.[1]
The termpathogen came into use in the 1880s.[2][3] Typically, the termpathogen is used to describe aninfectiousmicroorganism or agent, such as a virus, bacterium,protozoan,prion,viroid, orfungus.[4][5][6] Small animals, such ashelminths and insects, can also cause ortransmit disease. However, these animals are usually referred to asparasites rather than pathogens.[7] The scientific study of microscopic organisms, including microscopic pathogenic organisms, is calledmicrobiology, whileparasitology refers to the scientific study of parasites and the organisms that host them.
There are several pathways through which pathogens can invade a host. The principal pathways have different episodic time frames, butsoil has the longest or most persistent potential for harboring a pathogen.
Pathogenicity is the potential disease-causing capacity of pathogens, involving a combination ofinfectivity (pathogen's ability to infect hosts) andvirulence (severity of host disease).Koch's postulates are used to establish causal relationships between microbial pathogens and diseases. Whereasmeningitis can be caused by a variety of bacterial, viral, fungal, and parasitic pathogens,cholera is only caused by some strains ofVibrio cholerae. Additionally, some pathogens may only cause disease in hosts with animmunodeficiency. Theseopportunistic infections often involvehospital-acquired infections among patients already combating another condition.[8]
Infectivity involvespathogen transmission through direct contact with the bodily fluids or airborne droplets of infected hosts, indirect contact involving contaminated areas/items, or transfer by livingvectors likemosquitos andticks. Thebasic reproduction number of an infection is the expected number of subsequent cases it is likely to cause through transmission.[9]
Virulence involves pathogens extracting host nutrients for their survival, evading host immune systems by producingmicrobial toxins and causingimmunosuppression.Optimal virulence describes a theorized equilibrium between a pathogen spreading to additional hosts to parasitize resources, while lowering their virulence to keep hosts living forvertical transmission to their offspring.[10]
Algae include single-celledeukaryotes that are generally non-pathogenic. Green algae from the genusPrototheca lack chlorophyll and are known to cause the diseaseprotothecosis in humans, dogs, cats, and cattle, typically involving the soil-associated speciesPrototheca wickerhamii.[11][12][13]
Bacteria are single-celledprokaryotes that range in size from 0.15 and 700 μM.[14] While the vast majority are either harmless or beneficial to their hosts, such as members of thehuman gut microbiome that support digestion, a small percentage are pathogenic and cause infectious diseases. Bacterialvirulence factors include adherence factors to attach to host cells, invasion factors supporting entry into host cells,capsules to preventopsonization andphagocytosis, toxins, andsiderophores to acquire iron.[15]
A photomicrograph of a stool that has shigella dysentery. These bacteria typically cause foodborne illness.
Fungi are eukaryotic organisms that can function as pathogens. There are approximately 300 known fungi that are pathogenic to humans, includingCandida albicans, which is the most common cause ofthrush, andCryptococcus neoformans, which can cause a severe form ofmeningitis.[19] Typical fungal spores are 4.7 μm long or smaller.[20]
Magnified 100× and stained. This photomicrograph of the brain tissue shows the presence of the prominent spongiotic changes in the cortex, with the loss of neurons in a case of a variant of Creutzfeldt-Jakob disease (vCJD)
Prions are misfolded proteins that transmit their abnormal folding pattern to other copies of the protein without usingnucleic acids. Besides obtaining prions from others, these misfolded proteins arise from genetic differences, either due to family history or sporadic mutations.[21] Plants uptake prions from contaminated soil and transport them into their stem and leaves, potentially transmitting the prions toherbivorous animals.[22] Additionally, wood, rocks, plastic, glass, cement, stainless steel, and aluminum have been shown binding, retaining, and releasing prions, showcasing that the proteins resist environmental degradation.[23]
While prions are typically viewed as pathogens that cause proteinamyloid fibers to accumulate into neurodegenerative plaques,Susan Lindquist led research showing that yeast use prions to pass on evolutionarily beneficial traits.[25]
Not to be confused withvirusoids or viruses, viroids are the smallest known infectious pathogens. Viroids are small single-stranded, circular RNA that are only known to cause plant diseases, such as thepotato spindle tuber viroid that affects various agricultural crops. Viroid RNA is not protected by a protein coat, and it does not encode any proteins, only acting as aribozyme to catalyze other biochemical reactions.[26]
Viruses are generally between 20–200 nm in diameter.[27] For survival and replication, viruses inject their genome into host cells, insert those genes into the host genome, and hijack the host's machinery to produce hundreds of new viruses until the cell bursts open to release them for additional infections. Thelytic cycle describes this active state of rapidly killing hosts, while thelysogenic cycle describes potentially hundreds of years of dormancy while integrated in the host genome.[28] Alongside the taxonomy organized by theInternational Committee on Taxonomy of Viruses (ICTV), theBaltimore classification separates viruses by seven classes ofmRNA production:[29]
Parasitic worms (helminths) are macroparasites that can be seen by the naked eye. Worms live and feed in their living host, acquiring nutrients and shelter in the digestive tract or bloodstream of their host. They also manipulate the host's immune system by secreting immunomodulatory products which allows them to live in their host for years.[31]Helminthiasis is the generalized term for parasitic worm infections, which typically involveroundworms,tapeworms, andflatworms.[32]
While bacteria are typically viewed as pathogens, they serve as hosts tobacteriophage viruses (commonly known as phages). The bacteriophage life cycle involves the viruses injecting their genome into bacterial cells, inserting those genes into the bacterial genome, and hijacking the bacteria's machinery to produce hundreds of new phages until the cell bursts open to release them for additional infections. Typically, bacteriophages are only capable of infecting a specific species or strain.[33]
Streptococcus pyogenes uses aCas9nuclease to cleave foreign DNA matching the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated with bacteriophages, removing the viral genes to avoid infection. This mechanism has been modified for artificialCRISPR gene editing.[34]
Plants can play host to a wide range of pathogen types, including viruses, bacteria, fungi, nematodes, and even other plants.[35] Notable plant viruses include thepapaya ringspot virus, which has caused millions of dollars of damage to farmers in Hawaii and Southeast Asia,[36] and thetobacco mosaic virus which caused scientistMartinus Beijerinck to coin the term "virus" in 1898.[37] Bacterialplant pathogens cause leaf spots, blight, and rot in many plant species.[38] The most common bacterial pathogens for plants arePseudomonas syringae andRalstonia solanacearum, which cause leaf browning and other issues in potatoes, tomatoes, and bananas.[38]
Brown rot fungal disease on an apple. Brown rot typically target a variety of top-fruits.
Fungi are another major pathogen type for plants. They can cause a wide variety of issues such as shorter plant height, growths or pits on tree trunks, root or seed rot, and leaf spots.[39] Common and serious plant fungi include therice blast fungus,Dutch elm disease,chestnut blight and theblack knot andbrown rot diseases of cherries, plums, and peaches. It is estimated that pathogenic fungi alone cause up to a 65% reduction in crop yield.[38]
Overall, plants have a wide array of pathogens and it has been estimated that only 3% of the disease caused by plant pathogens can be managed.[38]
Animals often get infected with many of the same or similar pathogens as humans including prions, viruses, bacteria, and fungi. While wild animals often get illnesses, the larger danger is for livestock animals. It is estimated that in rural settings, 90% or more of livestock deaths can be attributed to pathogens.[40][41] Animal transmissible spongiform encephalopathy (TSEs) involving prions includebovine spongiform encephalopathy (mad cow disease),chronic wasting disease,scrapie,transmissible mink encephalopathy,feline spongiform encephalopathy, and ungulate spongiform encephalopathy.[24][42] Other animal diseases include a variety of immunodeficiency disorders caused by viruses related to human immunodeficiency virus (HIV), such asBIV andFIV.[43]
Humans can be infected with many types of pathogens, including prions, viruses, bacteria, and fungi, causing symptoms like sneezing, coughing, fever, vomiting, and potentially lethalorgan failure. While some symptoms are caused by the pathogenic infection, others are caused by the immune system's efforts to kill the pathogen, such as feverishly high body temperatures meant todenature pathogenic cells.[4]
A variety of prevention and treatment options exist for some viral pathogens.Vaccines are one common and effective preventive measure against a variety of viral pathogens.[45] Vaccines prime the immune system of the host, so that when the potential host encounters the virus in the wild, the immune system can defend against infection quickly. Vaccines designed against viruses include annualinfluenza vaccines and the two-doseMMR vaccine againstmeasles,mumps, andrubella.[46] Vaccines are not available against the viruses responsible forHIV/AIDS,dengue, andchikungunya.[47]
Treatment of viral infections often involves treating the symptoms of the infection, rather than providing medication to combat the viral pathogen itself.[48][49] Treating the symptoms of a viral infection gives the host immune system time to develop antibodies against the viral pathogen. However, for HIV,highly active antiretroviral therapy (HAART) is conducted to prevent the viral disease from progressing into AIDS as immune cells are lost.[50]
A structure of Doxycycline a tetracycline-class antibiotic
Much like viral pathogens, infection by certain bacterial pathogens can be prevented via vaccines.[46] Vaccines against bacterial pathogens include theanthrax vaccine andpneumococcal vaccine. Many other bacterial pathogens lack vaccines as a preventive measure, but infection by these bacteria can often be treated or prevented withantibiotics. Common antibiotics includeamoxicillin,ciprofloxacin, anddoxycycline. Each antibiotic has different bacteria that it is effective against and has different mechanisms to kill that bacteria. For example,doxycycline inhibits the synthesis of new proteins in bothgram-negative andgram-positive bacteria, which makes it abroad-spectrum antibiotic capable of killing most bacterial species.[51]
Due to misuse of antibiotics, such as prematurely ended prescriptions exposing bacteria toevolutionary pressure under sublethal doses, some bacterial pathogens have developedantibiotic resistance.[52] For example, a genetically distinct strain ofStaphylococcus aureus calledMRSA is resistant to the commonly prescribedbeta-lactam antibiotics. A 2013 report from theCenters for Disease Control and Prevention (CDC) estimated that in the United States, at least 2 million people get an antibiotic-resistant bacterial infection annually, with at least 23,000 of those patients dying from the infection.[53]
Due to their indispensability in combating bacteria, new antibiotics are required for medical care. One target for new antimicrobial medications involves inhibitingDNA methyltransferases, as these proteins control the levels of expression for other genes, such as those encoding virulence factors.[54][55]
Infection by fungal pathogens is treated with anti-fungal medication.Athlete's foot,jock itch, andringworm are fungal skin infections that are treated with topical anti-fungal medications likeclotrimazole.[56] Infections involving the yeast speciesCandida albicans causeoral thrush andvaginal yeast infections. These internal infections can either be treated with anti-fungal creams or with oral medication. Common anti-fungal drugs for internal infections include theechinocandin family of drugs andfluconazole.[57]
While algae are commonly not thought of as pathogens, the genusPrototheca causes disease in humans.[58][13] Treatment forprotothecosis is currently under investigation, and there is no consistency in clinical treatment.[13]
Viruses may also undergo sexual interaction when two or more viralgenomes enter the same host cell. This process involves pairing of homologous genomes and recombination between them by a process referred to as multiplicity reactivation. Theherpes simplex virus,human immunodeficiency virus, andvaccinia virus undergo this form of sexual interaction.[59]
These processes of sexual recombination between homologous genomes supportsrepairs to genetic damage caused by environmental stressors and host immune systems.[60]
^abAlberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002)."Introduction to Pathogens".Molecular Biology of the Cell (4th ed.). Garland Science.
^Beijerinck MW (1898). "Über ein Contagium vivum fluidum als Ursache der Fleckenkrankheit der Tabaksblätter".Verhandelingen der Koninklijke Akademie van Wetenschappen te Amsterdam (in German).65:1–22.;"About a contagium vivum fluidum as a cause of the spot disease of tobacco leaves"(PDF).Phytopathological Classics.7. Translated by Johnson J. St. Paul, Minnesota: American Phytopathological Society:33–52. 1942.
^Forloni G, Artuso V, Roiter I, Morbin M, Tagliavini F (2013-09-30). "Therapy in prion diseases".Current Topics in Medicinal Chemistry.13 (19):2465–76.doi:10.2174/15680266113136660173.PMID24059336.
%2c_H%2526E.jpg)
