Testing of the antifungal activity of oleylphosphocholine on Candida albicans planktonic cells and biofilms developed in vitro and in vivo in a subcutaneous biofilm model

jurgen wuyts
Wapenwedloop: de mens versus het minusculeWe worden steeds ouder, maar voor hoe lang nog? Voor de Tweede Wereldoorlog waren antibiotica nog niet ontdekt. In die tijd lag de levensverwachting rond de 50 jaar. Toen na Tweede Wereldoorlog penicilline ontdekt en verspreid werd, steeg de levensverwachting snel. Niet lang daarna werden al de eerste resistente bacteriën ontdekt waardoor onze lange levensverwachting nu in het gedrang komt. . Resistentiemechanismen van bacteriën en schimmelsMaar wat betekent resistentie nu eigenlijk? Wel, bacteriën en schimmels kunnen antibiotica onschadelijk maken.

Testing of the antifungal activity of oleylphosphocholine on Candida albicans planktonic cells and biofilms developed in vitro and in vivo in a subcutaneous biofilm model

Wapenwedloop: de mens versus het minuscule

We worden steeds ouder, maar voor hoe lang nog? Voor de Tweede Wereldoorlog waren antibiotica nog niet ontdekt. In die tijd lag de levensverwachting rond de 50 jaar. Toen na Tweede Wereldoorlog penicilline ontdekt en verspreid werd, steeg de levensverwachting snel. Niet lang daarna werden al de eerste resistente bacteriën ontdekt waardoor onze lange levensverwachting nu in het gedrang komt. .

Resistentiemechanismen van bacteriën en schimmels

Maar wat betekent resistentie nu eigenlijk? Wel, bacteriën en schimmels kunnen antibiotica onschadelijk maken. Zo kunnen ze bijvoorbeeld de antibiotica uit de cel pompen of de concentratie van het eiwit waarop het antibiotica werkt verhogen. Hierdoor zijn de bacteriën in staat te overleven en verliezen de antibiotica hun werking. De gevolgen hiervan zijn rampzalig. Een banale infectie kan plots levensbedreigend worden. Erger nog, sommige bacteriën hebben mechanismen om meerdere antibiotica te omzeilen. Hierdoor hebben ze zelfs een voordeel tegenover andere bacteriën. Deze zogenaamde ‘ziekenhuisbacterie’ is nu al verantwoordelijk voor duizenden doden op jaarbasis.

Antibiotica als redmiddel

De ontwikkeling van nieuwe antibiotica is duur en neemt veel tijd in beslag. Ze brengen weinig op in vergelijking met medicijnen tegen chronische ziektes en zijn vaak gebaseerd op bestaande antibiotica. Hierdoor worden bacteriën en schimmels sneller resistent. Grote farmaceutische bedrijven zijn dan ook minder geneigd nieuwe antibiotica te ontwikkelen. Dit vormt een serieuze bedreiging voor de gezondheidszorg. Toch is het noodzakelijk continu nieuwe antibiotica te ontwikkelen om de resistentiemechanismen te omzeilen. Alleen zo kunnen we ook in de toekomst de strijd aangaan met bacteriën en schimmels.

Schimmels vormen biofilms

Candida albicans is een schimmel die iedereen met zich meedraagt zonder veel problemen, maar kan levensbedreigend worden onder de juiste omstandigheden. Deze schimmel vormt vooral een ernstig gevaar bij mensen met een verzwakt immuunsysteem. Verder staat deze schimmel bekend om een biofilm te vormen op implantaten zoals katheters of pacemakers. Deze biofilm is bijna niet uit te roeien met conventionele antibiotica en bijgevolg dient een geïnfecteerd implantaat steeds verwijderd te worden.

Oleylphosphocholine: een nieuw antischimmelmiddel?

Tijdens mijn thesis heb ik het potentieel van oleylphosphocholine (OIPC) onderzocht als nieuw antischimmelmiddel. OIPC is een stof die eerder ontwikkeld werd als antikankermiddel, maar bleek achteraf niet te werken in mensen. Het potentieel van deze stof werd getest tegen de schimmel Candida albicans. Biofilmen werden gevormd op catheters. Hier werden verschillende concentraties OIPC aan toegevoegd. Hieruit bleek dat OIPC een heel goede antischimmelactiviteit heeft. Om na te gaan of dit ook het geval zou kunnen zijn in mensen werd OIPC eerst getest op muizen. Geïnfecteerde katheters werden ingeplant in muizen en gedurende 7 dagen werd OIPC toegediend. Hier was het antischimmelmiddel echter minder effectief.

De toekomst gegarandeerd?

Het ontwikkelen van nieuwe antibiotica verloopt moeizaam en vele potentiële kandidaten falen tijdens de ontwikkeling. Daarom is het noodzakelijk dat iedereen verantwoord omgaat met antibiotica. Zo neem je best geen antibiotica in bij virale infecties, ze werken toch niet tegen virussen. Bij je volgende verkoudheid neem je dus best geen antibiotica in. Het buitenspel zetten van resistente bacteriën is een harde strijd, maar een strijd die desalniettemin gevochten zal moeten worden om onze levensverwachting in te toekomst te garanderen. 

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Websites

http://labeling.pfizer.com/ShowLabeling.aspx?id=566

http://www.medchemexpress.com/miltefosine.htmL

http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=5476&lvl=3&lin=f&keep=1&srchmode=1&unlock

http://www.pfizer.com/files/products/uspi_fluconazole.pdf

https://www.ambisome.com/MOA.aspx

https://www.merck.com/product/usa/pi_circulars/c/cancidas/cancidas_pi.pdf

 

 

 

 

Universiteit of Hogeschool
biochemie & biotechnologie
Publicatiejaar
2015
Kernwoorden
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