Faagicocktail-erojen vaikutus E. coli –bakteerien hävittämisen tehokkuuteen

Antibioottiresistenssi on yksi nykymaailman suurimmista lääketieteellisistä uhista, sillä vastustuskykyisten bakteeri-infektioiden hoito on hankalaa tai mahdotonta. Antibioottien rinnalle tarvitaan nopeasti uusia hoitomuotoja bakteeri-infektioita vastaan. Yksi mahdollinen vaihtoehto bakteeri-infe...

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Päätekijä: Nykänen, Eino
Muut tekijät: Matemaattis-luonnontieteellinen tiedekunta, Faculty of Sciences, Bio- ja ympäristötieteiden laitos, Department of Biological and Environmental Science, Jyväskylän yliopisto, University of Jyväskylä
Aineistotyyppi: Pro gradu
Kieli:fin
Julkaistu: 2025
Aiheet:
Linkit: https://jyx.jyu.fi/handle/123456789/100752
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author Nykänen, Eino
author2 Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_facet Nykänen, Eino Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä Nykänen, Eino Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_sort Nykänen, Eino
datasource_str_mv jyx
description Antibioottiresistenssi on yksi nykymaailman suurimmista lääketieteellisistä uhista, sillä vastustuskykyisten bakteeri-infektioiden hoito on hankalaa tai mahdotonta. Antibioottien rinnalle tarvitaan nopeasti uusia hoitomuotoja bakteeri-infektioita vastaan. Yksi mahdollinen vaihtoehto bakteeri-infektioiden hoitamiseen on faagiterapia, jossa bakteriofageja, eli ainoastaan bakteereja tuhoavia viruksia käytetään antibakteerisessa hoidossa. Faagiterapian yksi kulmakivistä on faagicocktailit, eli useamman samaa bakteerikantaa infektoivan bakteriofagin käyttö samanaikaisesti. Faagicocktailien tarkoituksena on vähentää bakteerien kykyä muodostaa vastustus bakteriofagien infektiolle. Faagicocktailien muodostamisen haasteena on löytää mahdollisimman erilaisten infektiomekanismien omaavia bakteriofageja, jotka kuitenkin infektoivat samaa bakteerikantaa. Tähän ongelmaan vastauksena PrecisionPhage Oy on kehittänyt laskennallisen työkalun CocktailShakerin, jonka tarkoituksena on muodostaa bakteriofagien rakenteiden perusteella tehokkaita faagicocktailehdotuksia faagiterapiaa varten. Tässä tutkielmassa CocktailShakerin luotettavuutta testattiin kokeellisesti, vertaamalla laskennallisesti valitun ja satunnaisesti valittujen faagicocktailien kykyä tuhota antibioottiresistentin Escherichia coli – bakteerin EC10 –kantaa. Tulokset osoittivat kaikkien valittujen faagicocktailien estävän tehokkaasti EC10-kannan kasvua. Eroja faagicocktailien tehokkuudessa ilmeni vasta pienillä faagipitoisuuksilla, eikä CocktailShakerin valitsema faagicocktail osoittautunut satunnaisesti valittuja cocktaileja paremmaksi. Kokeessa käytetyt faagit osoittautuivat harvinaisen tehokkaiksi, ja sen vuoksi cocktailin koostumuksella ei ollut niin suurta merkitystä. Faagien fylogeneettisillä eroilla puolestaan osoittautui olevan vaikutusta faagicocktailien tehokkuuteen, mikä voi antaa uuttaa suuntaa faagicocktailien ja laskennallisten algoritmien kehittämiseen. Antibiotic resistance is one of the major threats in modern health care. Treatment of resistant bacterial infections is difficult or impossible so there is vital need for new treatments alongside antibiotics. One possible treatment against bacterial infections is phage therapy. In phage therapy bacteriophages are used in antibacterial treatment. Bacteriophages are viruses which infect only bacteria. One of the cornerstones in phage therapy is phage cocktails. Phage cocktails are formed from several bacteriophages which are infected by the same bacteria strains. The main goal of using phage cocktails is to reduce the ability of bacteria to form resistance to bacteriophage infection. However, there is one big challenge to make phage cocktails. It is demanding to find bacteriophages with sufficiently different infection mechanisms, and which infect the same bacteria strain. In response to that problem PrecisionPhage Ltd. has developed a computational tool named CocktailShaker which intention is producing proposals of effective phage cocktails used in phage therapy. The CocktailShaker makes proposals based on structures of bacteriophages. In this experiment, the ability of computationally selected phage cocktail and randomly selected phage cocktails to eradicate an antibiotic resistance Escherichia coli strain EC10, were studied. Results showed that all selected phage cocktails were highly efficient against EC10 strain. Differences in the ability of the cocktails to eradicate bacteria were reached only in lower phage concentrations. CocktailShaker prediction did not turn out to be better than randomly selected cocktails because phages turned out to be extremely effective and therefore the composition of the cocktail was not so important. One of the important observations was that phylogenetic differences between phages of the cocktails would seem to have a big impact on the inhibition efficiency to the bacteria growth. These findings may give a new direction to the development of the computational algorithms and phage cocktails.
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Antibioottien rinnalle tarvitaan nopeasti uusia hoitomuotoja \nbakteeri-infektioita vastaan. Yksi mahdollinen vaihtoehto bakteeri-infektioiden\nhoitamiseen on faagiterapia, jossa bakteriofageja, eli ainoastaan bakteereja \ntuhoavia viruksia k\u00e4ytet\u00e4\u00e4n antibakteerisessa hoidossa. Faagiterapian yksi \nkulmakivist\u00e4 on faagicocktailit, eli useamman samaa bakteerikantaa infektoivan \nbakteriofagin k\u00e4ytt\u00f6 samanaikaisesti. Faagicocktailien tarkoituksena on \nv\u00e4hent\u00e4\u00e4 bakteerien kyky\u00e4 muodostaa vastustus bakteriofagien infektiolle. \nFaagicocktailien muodostamisen haasteena on l\u00f6yt\u00e4\u00e4 mahdollisimman erilaisten \ninfektiomekanismien omaavia bakteriofageja, jotka kuitenkin infektoivat samaa \nbakteerikantaa. T\u00e4h\u00e4n ongelmaan vastauksena PrecisionPhage Oy on kehitt\u00e4nyt \nlaskennallisen ty\u00f6kalun CocktailShakerin, jonka tarkoituksena on muodostaa \nbakteriofagien rakenteiden perusteella tehokkaita faagicocktailehdotuksia \nfaagiterapiaa varten. T\u00e4ss\u00e4 tutkielmassa CocktailShakerin luotettavuutta \ntestattiin kokeellisesti, vertaamalla laskennallisesti valitun ja satunnaisesti \nvalittujen faagicocktailien kyky\u00e4 tuhota antibioottiresistentin Escherichia coli \u2013\nbakteerin EC10 \u2013kantaa. Tulokset osoittivat kaikkien valittujen faagicocktailien \nest\u00e4v\u00e4n tehokkaasti EC10-kannan kasvua. Eroja faagicocktailien tehokkuudessa \nilmeni vasta pienill\u00e4 faagipitoisuuksilla, eik\u00e4 CocktailShakerin valitsema \nfaagicocktail osoittautunut satunnaisesti valittuja cocktaileja paremmaksi. \nKokeessa k\u00e4ytetyt faagit osoittautuivat harvinaisen tehokkaiksi, ja sen vuoksi \ncocktailin koostumuksella ei ollut niin suurta merkityst\u00e4. Faagien \nfylogeneettisill\u00e4 eroilla puolestaan osoittautui olevan vaikutusta faagicocktailien \ntehokkuuteen, mik\u00e4 voi antaa uuttaa suuntaa faagicocktailien ja laskennallisten \nalgoritmien kehitt\u00e4miseen.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Antibiotic resistance is one of the major threats in modern health care. Treatment \nof resistant bacterial infections is difficult or impossible so there is vital need for \nnew treatments alongside antibiotics. One possible treatment against bacterial \ninfections is phage therapy. In phage therapy bacteriophages are used in \nantibacterial treatment. Bacteriophages are viruses which infect only bacteria. \nOne of the cornerstones in phage therapy is phage cocktails. Phage cocktails are \nformed from several bacteriophages which are infected by the same bacteria \nstrains. The main goal of using phage cocktails is to reduce the ability of bacteria \nto form resistance to bacteriophage infection. However, there is one big challenge \nto make phage cocktails. It is demanding to find bacteriophages with sufficiently \ndifferent infection mechanisms, and which infect the same bacteria strain. In \nresponse to that problem PrecisionPhage Ltd. has developed a computational \ntool named CocktailShaker which intention is producing proposals of effective \nphage cocktails used in phage therapy. The CocktailShaker makes proposals \nbased on structures of bacteriophages. In this experiment, the ability of \ncomputationally selected phage cocktail and randomly selected phage cocktails \nto eradicate an antibiotic resistance Escherichia coli strain EC10, were studied. \nResults showed that all selected phage cocktails were highly efficient against \nEC10 strain. Differences in the ability of the cocktails to eradicate bacteria were \nreached only in lower phage concentrations. CocktailShaker prediction did not\nturn out to be better than randomly selected cocktails because phages turned out \nto be extremely effective and therefore the composition of the cocktail was not so \nimportant. One of the important observations was that phylogenetic differences \nbetween phages of the cocktails would seem to have a big impact on the \ninhibition efficiency to the bacteria growth. 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spellingShingle Nykänen, Eino Faagicocktail-erojen vaikutus E. coli –bakteerien hävittämisen tehokkuuteen Solu- ja molekyylibiologia Cell and molecular biology bakteriofagit bakteeritaudit mikrobiologia antibiootit resistenssi fagiterapia
title Faagicocktail-erojen vaikutus E. coli –bakteerien hävittämisen tehokkuuteen
title_full Faagicocktail-erojen vaikutus E. coli –bakteerien hävittämisen tehokkuuteen
title_fullStr Faagicocktail-erojen vaikutus E. coli –bakteerien hävittämisen tehokkuuteen Faagicocktail-erojen vaikutus E. coli –bakteerien hävittämisen tehokkuuteen
title_full_unstemmed Faagicocktail-erojen vaikutus E. coli –bakteerien hävittämisen tehokkuuteen Faagicocktail-erojen vaikutus E. coli –bakteerien hävittämisen tehokkuuteen
title_short Faagicocktail-erojen vaikutus E. coli –bakteerien hävittämisen tehokkuuteen
title_sort faagicocktail erojen vaikutus e coli bakteerien hävittämisen tehokkuuteen
title_txtP Faagicocktail-erojen vaikutus E. coli –bakteerien hävittämisen tehokkuuteen
topic Solu- ja molekyylibiologia Cell and molecular biology bakteriofagit bakteeritaudit mikrobiologia antibiootit resistenssi fagiterapia
topic_facet Cell and molecular biology Solu- ja molekyylibiologia antibiootit bakteeritaudit bakteriofagit fagiterapia mikrobiologia resistenssi
url https://jyx.jyu.fi/handle/123456789/100752 http://www.urn.fi/URN:NBN:fi:jyu-202503182567
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