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[{"key": "dc.contributor.advisor", "value": "Parikka, Mataleena", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Jalasvuori, Matti", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Lintil\u00e4, Emilia", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2024-06-19T09:13:30Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2024-06-19T09:13:30Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2024", "language": "", "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/96019", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Tuberkuloosi on infektiosairaus, jonka aiheuttaja on bakteeri Mycobacterium tuberculosis. Vuosittain tuberkuloosin sairastuu yli 10 miljoonaa ihmist\u00e4 ymp\u00e4ri maailman, ja sairaus aiheuttaa kuolleisuutta etenkin lapsissa ja muissa immuunipuutteisissa v\u00e4est\u00f6ryhmiss\u00e4. Yleisesti tuberkuloosin hoidossa on k\u00e4yt\u00f6ss\u00e4 nelj\u00e4n eri antibiootin yhdistelm\u00e4. Hoito on pitk\u00e4, kest\u00e4en yleens\u00e4 v\u00e4hint\u00e4\u00e4n kuusi kuukautta. Lis\u00e4ksi M. tuberculosis on luontaisesti tolerantti monille antibiooteille, sill\u00e4 se kykenee muun muassa vaipumaan lepotilaan sek\u00e4 piilottelemaan itsetuotetussa, soluv\u00e4liaineesta koostuvassa biofilmiss\u00e4. Pitkittyv\u00e4 hoito my\u00f6s lis\u00e4\u00e4 riski\u00e4 geneettisesti resistenttien kantojen syntyyn. Uusia strategioita tarvitaankin tehostamaan tuberkuloosin hoitoa, jotta my\u00f6s tolerantit bakteerit saadaan tehokkaasti eliminoitua infektion aikana. Tehosteaineiden k\u00e4ytt\u00f6 antibioottien rinnalla on yksi mahdollinen tapa saada antibiootit tehoamaan paremmin. Jotkin yhdisteet voivat toimia biofilmi-inhibiittoreina est\u00e4en biofilmin synty\u00e4 tai hajottaen biofilmin rakennetta, jolloin antibiootit saavuttavat biofilmiss\u00e4 el\u00e4v\u00e4t bakteerit paremmin. T\u00e4m\u00e4n pro gradu -tutkielman tarkoituksena olikin selvitt\u00e4\u00e4 25:n uuden johdannaisen potentiaali toimia biofilmin rakennetta heikent\u00e4v\u00e4n\u00e4 tehosteyhdisteen\u00e4 tavallisesti tuberkuloosin hoidossa k\u00e4ytetylle antibiootille, rifampisiinille. Tehokkuuttta tutkittiin Lux MDK (minimum duration of killing) -koeasetelmalla. Lux MDK-analyysi perustuu luminesenssin muutokseen, kun bioluminesenssia tuottavan bakteerin kasvua inhiboidaan antibakteerisilla aineilla. Tulokset vahvistettiin CFU maljaukseen perustuvalla MDK-analyysill\u00e4. Parhaiden yhdisteiden turvallisuutta testattiin my\u00f6s seeprakalan alkioille tehdyll\u00e4 toksisuustestauksella. Tutkimuksen mukaan yksi testatuista johdannaisista, JZP-AoF-249F, erottui muista tehokkuudessa. Se auttoi Lux MDK-analyysin perusteella rifampisiinia inhiboimaan 99 %:a koko bakteeripopulaatiosta kaksi kertaa nopeammin kuin rifampisiini, kun testikonsentraationa oli 40 \u00b5M. Lis\u00e4ksi yhdistelm\u00e4hoito eliminoi mykobakteereja CFU-maljauksen mukaan tilastollisesti merkitt\u00e4v\u00e4sti tehokkaammin kuin rifampisiini yksin kaikilla testatuilla konsentraatioilla. Yhdiste oli my\u00f6s toksisuustestin perusteella melko turvallinen (LC50=307.6 \u00b5M).", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Tuberculosis is an infectious disease which is caused by Mycobacterium tuberculosis. Annually over 10 million people fall ill with tuberculosis worldwide, and it causes mortality, especially among immunocompromised people and children. Tuberculosis is commonly treated with four first-line antibiotics. The treatment is long, lasting normally up to six to nine months. In addition, M. tuberculosis is naturally tolerant to many antibiotics because the bacteria can, for instance, enter a state of dormancy or hide in self-produced biofilm matrixes. The extensive treatment time also increases the risk of emerging genetically resistant strains. Because the current tuberculosis treatment is so inefficient, new strategies are needed to shorten the treatment and eliminate the tolerant sub-populations. One possible treatment strategy is to use adjunct compounds along with conventional antibiotics. The adjunct compounds could act as biofilm inhibitors which prevent the formation of biofilms or disrupt mature biofilms so that conventional antibiotics can target all bacteria in the infection site, including the tolerant sub-populations. Thus, this thesis aimed to study the killing efficacy of 25 new anti-biofilm compounds against mycobacterial biofilms when used with a conventional antibiotic, rifampicin. The efficacy was studied using Lux MDK (minimum duration of killing) -assay and CFU (colony forming unit) plating based MDK-assay. The idea of Lux MDK-assay is based on a change of bioluminescence when transgenic, bioluminescence-producing bacteria are eliminated from biofilms. CFU-plating was used to confirm that the treatment kills the bacteria and not just inhibits the growth. Additionally, the safety of the best compounds was studied with an acute embryonic toxicity test, in which, zebrafish embryos were exposed to the tested compounds. One hit compound, JZP-AoF-249F, was found in this study. Together with rifampicin, in the concentration of 40 \u00b5M, it inhibited the growth of 99% of the whole bacteria population twice as fast as rifampicin alone. In CFU plating the combination treatment of this compound and rifampicin was statistically significantly more efficient than rifampicin alone in all tested concentrations from 10 \u00b5M to 160 \u00b5M. According to the acute embryonic toxicity test, compound JZO-AoF-249F was also safe for the embryos with LC50 of 307.6 \u00b5M.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Miia Hakanen (mihakane@jyu.fi) on 2024-06-19T09:13:30Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2024-06-19T09:13:30Z (GMT). No. of bitstreams: 0\n Previous issue date: 2024", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "53", "language": "", "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.language.iso", "value": "eng", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "mycobacterium marinum", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "tolerance", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "JZP-AoF-compounds against mycobacterium biofilms : efficacy and safety", "language": "", "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-202406194784", "language": null, "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "yvv.contractresearch.funding", "value": "0", "language": "", "element": "contractresearch", "qualifier": "funding", "schema": "yvv"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "restrictedAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "4013", "language": "", "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "tuberkuloosi", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "biofilmit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "antibiootit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "mykobakteerit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "tuberculosis", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "biofilms", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "antibiotics", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "mycobacteria", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "The author has not given permission to make the work publicly available electronically. Therefore the material can be read only at the archival workstation at Jyv\u00e4skyl\u00e4 University Library (https://kirjasto.jyu.fi/collections/archival-workstation).", "language": "en", "element": "rights", "qualifier": "accessrights", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "Tekij\u00e4 ei ole antanut lupaa avoimeen julkaisuun, joten aineisto on luettavissa vain Jyv\u00e4skyl\u00e4n yliopiston kirjaston arkistoty\u00f6semalta. Ks. https://kirjasto.jyu.fi/kokoelmat/arkistotyoasema..", "language": "fi", "element": "rights", "qualifier": "accessrights", "schema": "dc"}]
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