Model Hosts Used To Determine Host Pathogen Interactions Biology Essay
In early century, microorganisms were considered as chief encroachers which ruled host-pathogen interaction doing disease. In early twentieth century, Smith recognized importance of host but continued to stress more microbic features as primilarily responsible for microbic virulency [ 1 ] . In his position, infective bugs were holding invading and supporting maps that separated them from non-pathogenic bugs which lead to the type and decision of host-pathogen interaction [ 1 ] .
Zinsser, explained the term pathogenic which means capable of doing disease, he suggested that virulency had 2 properties: ( I ) passive which possess microbic features such as capsules that allows stability in the host and ( two ) Aggressive which includes toxins, etc. [ 2 ] . Subsequently, it was found that the result of interaction between host and pathogen is a morbid status. This led to the beginning of footings commensalism, symbiosis, competition and parasitism. Commensalism refers to connexion between two where one being is benefited and other is neither benefited nor affected. On the other manus, relationship in which two dissimilar beings are benefited is called symbiosis.
Competition refers to the interaction in which both the beings are harmed and none is benefited. Whereas, symbiotic connexion between two beings out of which one known as parasite gets benefited at the cost of host is called parasitism. Koch ‘s posits which stated that: ( I ) There should be abundant microorganisms in all beings enduring from disease but none in unaffected animate beings.
( two ) Micro-organisms should be isolated from morbid being and should be grown in pure civilization. ( three ) The civilized being should do disease in healthy being when transfected. ( four ) The being should be once more isolated from inoculated, affected experimental host and recognized as indistinguishable to the original causative agent [ 3 ] , were non fulfilled as they were depicting behavior of bugs and non general relationship between host and pathogen. Recently, microbiologists reviewed the constructs of virulency and pathogencity and conveyed that microbic pathogenesis reflects interaction between host and pathogen.The thought of theoretical account being took topographic point in center of nineteenth century with the aid of Charles Darwin and Gregor Mendel with their work on “ Natural choice ” and “ Geneticss of heredity ” severally. Model beings are non-human species which are studied to derive better apprehension of biological phenomena with the hope that finds made in the being theoretical account will supply better penetration into the workings of other beings [ 4 ] . Model beings are classified as familial theoretical accounts ( e.
g. Drosophila melanogaster, Caenorhabditis elegans, etc. ) , experimental theoretical accounts ( e.g.
Xenopus laevis, etc. ) and genomic theoretical accounts ( e.g. Puffer fish, etc. ) . Often, exemplary beings are chosen on the footing that they are conformable to experimental use which normally includes features such as short life rhythm, familial use techniques, genome agreement and traits such as size, coevals clip, handiness, preservation of mechanisms and economic benefits. Multicellular non-mammalian hosts are used to analyze human diseases, to understand host-pathogen interactions, to analyze physical barriers, to analyze cellular mechanisms and molecular elements of the host response, to derive tonss of familial information to analyse development of worlds and for survey of cistron construction and ordinance.
Host-pathogen interaction consequences in assortment of responses like phagocytosis of pathogen, release of cytokines, secernment of toxins and production of reactive O species. The disadvantages of utilizing theoretical account beings are familial discrepancy, background cognition, reassign methodological analysis and deficiency of methodological analysis.Discussion:The table1 below shows non-mammalian theoretical account beings which are used hosts ( multicellular ) :Model beingFeaturesDrosophila melanogasterProvides consciousness of malignant neoplastic disease, encephalon diseases, behavior, unsusceptibility, aging, multiple cistrons heritage, and development.Caenorhabditis elegansTo analyze cell distinction and other developmental procedures in integral beings.Danio rerioUseful in mutational and infective surveies due to presence of crystalline egg embryologic developmental phase.Dictyostelium discoideumTo analyze cell distinction, signal transduction, cell screening etc.Galleria mellonellaUseful in in-vivo toxicology and pathogenecity testing.
Table 1: Non-mammalian multicellular theoretical account beingsDrosophila melanogasterDrosophila is normally known as fruit fly of acetum fly and belongs to household Drosophilidae. It is diphtheria which provenders and strains on spoilt fruits. It exhibits sexual dimorphism. It is used as a theoretical account for infective diseases in worlds and is an of import theoretical account for placing fresh cistrons and their merchandises which can activates host defense mechanism mechanisms. It is the first being used for familial analysis.
It is used for analyzing host pathogen interactions with Pseudomonas aeruginosa [ 5 ] , M. marinum [ 6 ] , Staphylococcus aureus [ 7 ] and L. monocytogenes [ 8 ] .
The outstanding characteristics of its life rhythm are a rapid period of embryogenesis followed by three periods of larval growing prior to metamorphosis as shown in fig1:Fig1: Life rhythm of Drosophila melanogaster [ 9,10 ]Understanding host-pathogen interactions between Listeria monocytogenes and Drosophila melanogaster:Listeria monocytogenes is an intracellular and facultative bacterial pathogen which has an ability to retroflex within wide scope of hosts. They were successful in doing deadly infections in grownup fruit flies and their larvae with reproduction of bacteriums before decease of host. Bacteria were present in the cytosol of phagocytic cells of insect and were possessing ability of triping polymerisation of host cell actin. For intracellular reproduction and cell-to-cell spreading within drosophila cells bacterial cistron merchandises were required. Furthermore, for look of L. monocytogenes virulency cistron the temperature should be more than 30 grades C.
But bacteriums within insect cells express virulency determiners at 25 grades C. Mutant strains which were compromised for innate unsusceptibility showed more susceptibleness to L. monocytogenes infection. This shows that infection of L.
monocytogenes of fruit flies shows many characteristics of mammalian infection which proves that Drosophila possess possible to function as a genetically manageable host system which will help the advancement of analysis of cellular response of host against L. monocytogenes infection [ 8 ] .Advantages of utilizing Drosophila melanogaster as a host theoretical account:Overall cost is low as attention and civilization requires small infinite and less equipments.It is easy to turn in research lab as it is little.
Easy to identifty its morphology after they are anesthetized.It has short coevals clip.It has high reproducing capableness.Familial mosaics permits analysis of deadly cistrons in grownup flies.Easy to make transgenic fruit flies which carries foreign DNA.
The first genome map was produced in Drosophila.Facilitates familial crossing as it ‘s easy to separate males and females and insulate virgin females.It has 3 autosomal chromosomes and one sex chromosome.The mature larva shows elephantine chromosome called polytene in salivary secretory organs of Drosophila which indicates zone of written text and therefore cistron activity.Its organ system is similar to mammals and so its physiology can be easy compared to mammals.
Disadvantages of utilizing Drosophila melanogaster as a host theoretical account:Coevals clip is longer than C. ElegansCan non stop dead.Homologous recombination is non easy.Does non demo advanced immune system like zebra fish.Danio rerioDanio rerio is normally known as Zebrafish. It lives in fresh H2O and is found in South Asia and is a common fish tank fish. It is an of import theoretical account being to analyze craniate ‘s development and disease, operation of variety meats, behavior and toxicology.
Its portions certain characteristics with worlds such as blood, kidney and optical system. Its genome is 50 per centum that of human and mouse genomes which helps in designation of of import craniate cistrons. It is used for analyzing host-pathogen interaction with Pseudomonas aeruginosa [ 11 ] , Streptococcus iniae [ 12 ] and Mycobacterium species [ 13 ] .
In life rhythm of D. rerio cleavage does non affect yolk ensuing into fertilized ovum on top of the yolk ( fig.2 ) .
Fig 2: Life rhythm of Danio rerio [ 14 ]Understanding host-pathogen interactions between Mycobacterium marinum and Danio rerio:Danio rerio are exposed to assorted sorts of mycobacterial pathogens like Mycobacterium fortuitum, Mycobacterium abscessus and mycobacteria chelonae [ 15 ] . M. Marinum is most exciting to analyze as it causes TB in fish. This pathogen has inauspicious consequence on the host and possess inclination to infect all animate beings with same efficiency. One job with M. Marinum infection is that fish can be infected for several hebdomads inveterate without clear symptoms, before they fall sick and get down to cast B.
The involvement in M. Marinum is due to its close relationship with M. TB and due to similarity of disease in fish to that of in worlds, with its characteristic continuity and granuloma formation. M. marinum is capable to last and undergo reproduction in grownup Zebrafish which leads to an ague or chronic disease on the footing of inoculants used [ 16 ] . Furthermore, the oucome of disease is due to the type of strain doing disease. M.
marinum strains can be divided into two bunchs depending on familial fingerprinting, and the bunch that possess most deadly strains besides contains mycobacteriums which are isolated from patients enduring from granulomas which is a skin infection caused by M. marinum [ 17 ] . In Zebrafish embryo theoretical account, embryologic macrophages infected with M. marinum erupts and begins to accumulate which leads to activation of certain cistrons in M. marinum which are evoked merely in enclosed environment of granuloma and non in isolated septic macrophages [ 18 ] . This shows that granuloma formation occurs in absence of lymph cells. Furthermore, Zebrafish mutations can be used to analyse collection of macrophages [ 18 ] . Zebrafish jaguar mutations are mutated in Zebrafish orthologue of the cistron which encodes macrophage-colony exciting factor-receptor.
The mutant macrophages are non able to assail embryologic tissues but signifiers clumps when infected by M. marinum. This reveals that this activity is non dependent on M-CSF [ 18 ] .
Therefore, this survey reveals the molecular interactions which lead to granuloma formation and continuity of mycobacterium.Advantages of utilizing Danio rerio as a host theoretical account:It has short coevals clip.Produce big figure of embryos per coupling.Allows all phases of development to be observed as development of transparent embryos occurs outside the female parent.Zebrafish is used as a theoretical account in analyzing assorted human diseases and procedure of aging.It has innate and immune system. It besides has complement system like worlds which activates by 3 different tracts: lectin, alternate and classical.
Familial showing and existent clip visual image is possible.They are easy to manage as they are little in size.They are easy to cultivate and shows rapid embryologic development.
They express few opposite numbers of human Toll like receptors ( TLR ) .Disadvantages of utilizing Danio rerio as a host theoretical account:They lack cell markers and cell lines.Gene duplicate and phylogenetics make it hard to place right orthologue or homologue opposite number.They can be used to analyze bacterial infections in existent clip but they lose transparence after 5-6 yearss.Gene omission.They have complex immune system.They contain merely sparsely arranged B and T cells.Galleria mellonellaG.
mellonella is by and large known as Greater wax moth or Honeycomb moth. Its larvae are effectual to analyze host pathogen interactions. It is used for survey host-pathogen interactions with Aspergillus fumigates [ 19 ] , Yersinia pseudotuberculosis [ 20 ] and Cryptococcus neoformans [ 21 ] . Y. Pseudotuberculosis is non harmful but it is infective in immunocompromized persons. The life rhythm of G. mellonella consists of 5 phases viz. egg, larva, whirling, pupa and grownup.
Understanding host-pathogen interactions between Galleria mellonella and Cryptococcus neoformans:Virulence of Cryptococcus neoformans in non-mammalian hosts suggests that C. neoformans is a non-specific pathogen. To analyze cryptococcal virulency, immune response of host to infection and effects of fungicidal compounds, G. mellonella is killed by C. neoformans so that an invertebrate host theoretical account system is developed.
After C. neoformans is injected into the insect hemocoel it proliferates and undergoes phagocytosis by host hemocytes and putting to deaths caterpillars at 37 every bit good as 30 degree C depending on cryptococcal strain and figure of fungous cells injected. It was found that H99 strain of C. neoformans was the most deadly strain of all and putting to deaths caterpillars with low inoculant. Even the cistrons of C.
neoformans like CAP59, GPA1, RAS1 and PKA1 plays an of import in killing the insect. Therefore, G. mellonella- C. neoformans pathogenicity theoretical account can be a substitute for mammalian theoretical accounts of infection and may help to analyze fungous virulency and efficaciousness of fungicidal therapies in vivo [ 21, 22, and 23 ] .Advantages of utilizing Galleria mellonella as a host theoretical account:Since larva shows susceptibleness to fungal infections and fungicidal agents their functions can be easy studied.It does non necessitate specific demands like microscopes, fly suites, etc.It can be cultivated at room temperature.
The larva exhibits systemic and local infection both.It is available at really low cost.Does non necessitate laboratory expertness to inoculate it as its size is merely 2.
5 centimeter.Disadvantages of utilizing Galleria mellonella as a host theoretical account:Complete sequenced genome is non available.Due to its complexness it is really hard to analyze response mechanism of this being to different Fungis.
Dictyostelium discoideum:D. discoideum grows as unicellular beings but upon famishment they aggregate to organize a multicellular tissue which is capable of distinguishing into several cell types. During this developmental period it undergoes many cellular procedures to organize a spore-bearing fruiting organic structure. This procedure includes chemotaxis, rearrangement of cytoskeleton, signal transduction, screening of cell and formation of form. D. Discoideum provides insight into procedures required for multicelluarity as its life rhythm consists of both uni- and multi-cellular stages as shown in fig.
3. It is used as a host theoretical account for several pathogens includingA Pseudomonas aeruginosa, Crytococcus neoformans, Mycobacterium spp. and Legionella pneumophila.Fig.3: Life of Dictyostelium discoideum [ 24 ]Understanding host-pathogen interaction between Dictyostelium discoideum and Legionella pneumophila:L. pneumophila is an intracellular bacterial pathogen which is capable of retroflexing inside D.
discoideum. Its ability to turn depends on growing province of cells. It follows same mechanism of growing in Dictyostelium as in ameba and macrophages.
This bacteria grows within membrane edge cysts which are associated with unsmooth endoplasmic Reticulum. The dot/icm mutation of the bacteriums which were blocked for growing in macrophages and ameba did non develop even in D. discoideum.
Internally, L. Pneumophila avoided debasement by D. discoideum and showed cut down merger with endocytic compartments.
During high degree of infection, when D. discoideum grows as adherent monolayer it was found to be susceptible to bacterial infection and to cytotoxicity, whereas when it was grown in suspension it was immune to cytotoxicity and therefore did non demo intracellular growing [ 25 ] .Advantages of utilizing Dictyostelium discoideum as a host theoretical account:It is easy to turn.Used in biomedical surveies.Has a rapid doubling clip.Allows frequent harvest home for survey.Due to both uni- and multicellular life rhythm it is an first-class theoretical account for developmental and cell biological science surveies.Facilitates mutant choice due to its simplw life rhythm.
Disadvantages of utilizing Dictyostelium discoideum as a host theoretical account:Glycosylation form varies.Industrial production of protein is non achieved in D. discoideum and therefore farther optimisations are required in bioprocessing and agitation.Caenorhabditis elegans:C. elegans is normally known as Roundworm. It is little, free life roundworm found in dirt. It is bacteriovorous as it feeds on bacteriums like E.
coli. It is diploid being holding two sex chromosomes and ten autosomal chromosomes. C. elegans is used to understand host pathogen interaction for gm positive bacteriums like Staphylococcus aureus, Enterococcus and Gram negative bacteriums like Salmonella typhimurium, Pseudomonas aeruginosa, serratia marcescenes and besides a fungus Cryptococcus neoformans, etc.
The short life rhythm of C. elegans shown in fig.4 facilitates familial experiments and is a major advantage for research workers working with this being.Fig.
4: Life rhythm of C. elegans [ 26 ]Understanding host-pathogen interaction between Caenorhabditis elegans and Staphylococcus aureus:S. aureus is a gram positive bacteria which is a taking cause of both community-acquired and hospital-acquired infections worldwide. It is an of import cause of bovine and ovine mastitis [ 27, 28 ] . It causes infection both in worlds every bit good as in C.
elegans. It causes infection by accretion of bacteriums in digestive piece of land and eventually kills the being. Some virulency determiners like Quarum feeling planetary virulency regulative system, planetary virulency regulator, V8 serine peptidases, alpha haemolysin and alternate sigma factor. Some mutations of C. elegans were susceptible to infection caused by S.
Aureus. Susceptibility of infection was enhanced in C. elegans when functional mutant of cistrons encoding p38 MAP tract was lost. This proves that there are some host factors in C. elegans which alter susceptibleness of gm positive pathogens [ 29 ] .Advantages of utilizing Caenorhabditis elegans as a host theoretical account:It is used to analyze malignant neoplastic disease and aging.Since it is crystalline, it is easy to detect utilizing fluorescent markers.It is easy to keep in research lab.
Its cell line of descent is good determined which makes it easier to analyze.It has a fast and convenient life rhythm.Though it is a simple being it shows the presence of a nervous system. Mechanisms like chemotaxis, thermotaxis can be studied.
Disadvantages of utilizing Caenorhabditis elegans as a host theoretical account:It size is really little which causes trouble to biochemical sums of roundworms at subsequently phase.Lack of cognition refering late-life pathology.It lacks unconditioned unsusceptibility.It can non last at 37 degree C at which pathogens cause infection in worlds.
Genetically they are non closely related to worlds.Decision:To reason, there are many facets of host-pathogen system that has been addressed by both experimental finds and computational theoretical accounts, though a comprehensive analysis of full host-pathogen interaction including pathogen intervention, host and pathogen response, etc. is a far-fetched end. Current theoretical accounts focus chiefly on host responses to infections or pathogenesity. Attempts are afoot to unite both pathogen action and host response in a comprehensive, intercrossed theoretical account, unifying attacks with “ omics ” [ 30 ] . Sophisticated experimental techniques such as protein look, tickets by quantum points for localisation and nano-biotechnological measurings on individual cells promise new penetrations into complexness of host-pathogen systems.
With regard to drug find, success narratives of utilizing theoretical account beings are still anecdotal. In future, patterning anticipations will most probably be merely inputs in determination devising procedure in pharmaceutical industries. A long-run end for host-pathogen systems biological science would include insilco theoretical accounts of an single human contending against infective interactions.