Netwerk-gebaseerde analyse van reactiewegen betrokken in Salmonella biofilmvorming
De digitale strijd tegen bacteriën
Bacteriën hebben een zeer sterk aanpassingsvermogen waardoor ze steeds nieuwe manieren vinden om te overleven. De mens moet daardoor steeds nieuwe geneesmiddelen zoeken om ze te bestrijden, maar de bronnen raken stilaan uitgeput. Zijn onze huidige verdedigingsstrategieën nog wel opgewassen tegen deze ‘die hards’ of is het tijd om de aanval in te zetten?
Alles of niets: wat zijn de kansen?
De bestrijding van een bepaalde bacterie is een alles of niets actie: als één bacterie overleeft, kan deze zich vermenigvuldigen zodat zijn nakomelingen weer in grote aantallen aanwezig zijn. Geen probleem zou je kunnen denken, we moeten ze alleen om de zoveel tijd eens aanpakken. Dat is inderdaad een mogelijke strategie, tenzij de overleving van deze ene bacterie gebaseerd is op een bepaalde aanpassing die het gebruikte geneesmiddel inactiveert. Alle nakomelingen zullen deze aanpassing ook hebben en het geneesmiddel zal geen van deze bacteriën meer kunnen doden.
In tegenstelling tot wat je zou vermoeden, zijn deze aanpassingen willekeurige processen. De bacterie kan een geneesmiddel enkel overleven als hij toevallig vanaf zijn ontstaan al de juiste aanpassing heeft. De kans hierop is zeer klein, maar één bacterie met de aanpassing is voldoende om het geneesmiddel voor eens en altijd te inactiveren. En de bacteriën zijn met heel veel, zodat dit fenomeen mogelijk is en ook effectief voorkomt.
De aanvalsstrategie
In het begin werd niet zoveel aandacht besteed aan de manier waarop geneesmiddelen bacteriën doden. Dat het werkte was het enige dat van belang was. De mens selecteerde dus eigenlijk net zoals de bacteriën zijn wapens per toeval. De stapel van geneesmiddelen die niet meer werken wordt echter steeds groter en die van nieuwe mogelijke geneesmiddelen is beperkt. Als we deze strijd willen winnen, zullen we het over een andere boeg moeten gooien. Daarom zijn wetenschappers tegenwoordig meer en meer op zoek naar de exacte werking van bepaalde geneesmiddelen, zodat ze bacteriën met verschillende geneesmiddelen op verschillende plaatsen tegelijk kunnen aanvallen.
De zoektocht naar de exacte werking van een bepaald geneesmiddel is echter vergelijkbaar met het zoeken naar een speld in een hooiberg. Eén bacterie bestaat al uit duizenden onderdelen en het kan zijn dat de uitschakeling van ééntje voldoende is om de bacterie te doden. Waar moeten we dus beginnen met zoeken?
Huidige technieken in het laboratorium laten toe om het effect van een bepaald geneesmiddel op de meerderheid van deze onderdelen apart te bestuderen. Hierdoor kunnen onderzoekers al een eerste idee krijgen van de werking ervan. Meestal zijn er meerdere onderdelen die beïnvloed worden door een bepaald geneesmiddel, wat aangeeft dat deze samenwerken in de bacterie. Het geneesmiddel werkt dan niet op elk van deze onderdelen apart, maar op één gemeenschappelijk onderdeel dat al de andere beïnvloedt. De werking van een bepaald geneesmiddel bepalen is het vinden van dit gemeenschappelijke onderdeel.
Het geheime wapen van de mens
Tegenwoordig weet men al veel over de samenwerkingen die tussen de onderdelen van een bacterie optreden, zodat het moeilijk wordt al deze informatie handmatig te doorzoeken zonder dingen over het hoofd te zien. Maar waarom zouden we in deze tijd nog dingen handmatig doorzoeken? We maken dagelijks gebruik van Google om informatie op het internet te doorzoeken! Waarom zouden we deze digitale technieken niet toepassen in de strijd tegen bacteriën?
In de biologie is er een specifiek domein, de bio-informatica, dat zich bezighoudt met dit soort toepassingen. Men kan al de beschikbare informatie over de onderdelen in een bepaalde bacterie bundelen en vervolgens doorzoeken met specifieke computerprogramma’s. Om deze zoektocht te vereenvoudigen worden de onderdelen in een bacterie voorgesteld als punten in een netwerk. De verbindingen in dit netwerk geven dan de samenwerking tussen verschillende onderdelen aan. Nu kunnen we zien hoe de onderdelen, die beïnvloed worden door een bepaald geneesmiddel, met elkaar verbonden zijn in dit netwerk en hopelijk een gemeenschappelijk onderdeel vinden.
De ultieme test
De scriptie “Netwerk-gebaseerde analyse van reactiewegen betrokken in Salmonella biofilmvorming” bestudeert of we via een netwerkanalyse, zoals in de vorige paragraaf beschreven, de werking van geneesmiddelen op de Salmonella bacterie kunnen bestuderen. Dit is de bacterie die voedselvergiftiging veroorzaakt als je niet doorbakken of slecht bewaard vlees eet. Bovendien verzamelen deze bacteriën zich in kleine kolonies, biofilmen genaamd, wat een extra verdedigingsmechanisme vormt tegen bestrijdingsmiddelen. Maar… door deze scriptie hebben we nu meer inzicht in dit verdedigingsmechanisme zodat we ons in de toekomst er beter tegen kunnen wapenen. En dat allemaal dankzij de toepassing van computertechnieken op biologische gegevens!
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