The role of cryptococcal 3-hydroxy fatty acids in mediating interspecies interactions

English: Cryptococcus neoformans is today recognised as an important human pathogen that has arisen from a non-pathogenic terrestrial fungus. Its interactions (specifically antagonistic interactions with other microbes (such as amoeba) in its natural habitat, soil, has led to cryptococcal cells evolving elegant offensive and defensive strategies to survive in nature. Importantly, these qualities seem to be maintained and activated whenever cryptococcal cells engage in antagonistic interactions with other cell types i.e. when in competition with Pseudomonas cells, which is the subject of chapter two, as well as when engaging in parasitism with macrophages, which is the subject of chapter three. Towards this end, in this dissertation, special attention was given to the role of the secondary metabolite, cryptococcal 3-hydroxy C9:0, in mediating the fate of C. neoformans when in contact with these other cell types. In chapter two, it was sought to explore the interactive outcome between cryptoccocal cells and Pseudomonas cells. Both cell types can, in their individual capacity, lead to the development of pneumonia. While the host body has optimal conditions (temperature, ambient air, etc.) to promote the growth of these two pathogens, their growth may be limited by the available nutrients within the confined space of the host lung. It is therefore reasonable to conclude that these microbes would engage in competition in order to exert territorial dominance over the other. To demonstrate this point in vitro, Pseudomonas cells were co-cultured with cryptococcal cells over a period of time. It was subsequently determined that cryptococcal cells dominated Pseudomonas cells. This domination manifested in a significant reduction (p = 0.05) in the number of Pseudomonas cells over a 24-h period. In order to determine if the observed domination could be as a result of the cryptococcal 3-hydroxy fatty acid, 3-OH-C9:0, negatively affecting the growth of Pseudomonas cells, Pseudomo
Afrikaans: Cryptococcus neoformans word tans erken as ‘n belnagrike menslike patogeen wat onstaan het vanaf ‘n nie-patogeniese terrestriële fungus. Sy interaksies (veral antagonistiese interaksies) met ander mikrobe (soos amoeba) in sy natuurlike habitat, grond, het daartoe gelei dat Cryptococcus selle elegante aanvals- en verdedigingstrategieë ontwikkel het om in die natuur te oorleef. Dit is van belang dat hierdie eienskaape blyk behou en geaktiveer te word wanneer Cryptococcus selle deelneem aan antagonistiese interaksies met ander tipes selle d.i. wanneer hulle kompeteer met Pseudomonas selle, die onderwerp van hoofstuk twee, asook wanneer hulle deelneem aan parasitisme met makrofage, die onderwerp van hoofstuk drie. Ter nastrewe van hierdie doel, word in hierdie verhandeling veral aandag gegee aan die rol van die sekondêre metaboliet, 3-hidroksie C9:0 (3-OH-C9:0) vanaf Cryptococcus, in bepaling van die lot van C. neoformans wanner dit in kontak is met hierdie ander seltipes. In hoofstuk twee is gepoog om die interaktiewe uitkoms tussen Cryptococcus selle en Pseudomonas selle te ondersoek. Beide seltipes kan individueel lei tot ontstaan van longontsteking. Alhoewel die gasheerliggaam optimale toestande (temperatuur, lug ens.) bevat om die groei van hierdie twee patogene te promoveer, mag hulle groei beperk word deur die beskikbare voedingstowwe binne die beperkte spasie van die gasheerlong. Dit kan dus redelikerwys afgelei word dat hierdie mikrobes sal deelneem aan kompetisie om territorial domanansie oor die ander uit te oefen. Om hierdie punt in vitro te demonstreer is Pseudomonas selle saam met Cryptococcus selle gekweek oor ‘n seker periode. Gevolglik is gevind dat Cryptococcus selle Pseudomonas selle domineer. Hierdie domineering het gemanifesteer as ‘n beduidende afname (p = 0.05) in die getal Pseudomonas selle oor ‘n tydperk van 24-h. Ten einde te bepaal of die waargeneemde dominering kan wees as gevolg van negatiewe invloed van die Cryptococcus 3-hidroks
National Research Foundation (NRF)
NMDS