Talaromyces marneffei is human fungal pathogen that infects immunocompromised patients and is endemic to southeast Asia, but a growing number of cases have been recently reported in other parts of the globe. Infections by this pathogen are generally associated with AIDS, therefore it has been named as AIDS defining pathogen, but an increasing number of cases in non-HIV patients have been documented. The fungal cell wall represents the first line of interaction between the pathogen and the host. The cell wall protects the fungal cell and is known to modulate the interaction with the host. Given its importance to the viability of the fungus, inhibitors that affect the fungal cell wall integrity are considered ideal targets for drug development. Moreover, the general conservation in composition of fungal cell walls means that it is possible to target both animal- and plant-pathogenic fungi with these compounds. By characterising the different components of cell wall, we can move towards discovering novel targets for antifungal drugs. We are also looking into the host-pathogen interactions at molecular level which will give us an insight of the phagocytosis and killing of this pathogen in its natural environment. This mechanism can be exploited through genetic manipulation to discover more natural targets for our antifungal drugs arsenal. This project is focused on some of the major  components of the cell wall such as β- glucans and their role in growth and pathogenicity. Mutant strains created by deleting the genes required to produce or assemble these cell wall components were characterised at  macroscopic and microscopic levels. Examination of the cell wall architecture and pattern of different cell wall components was done using field emission Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Gas chromatography-mass spectrometry (GC-MS) will be used to analyse the cell wall composition and different types of linkages inside the cell wall for wild type and deletion strains. It is known that cell wall composition is dynamic, so to assess whether the expression of genes associated with cell wall biogenesis was affected by the deletion of certain components,  levels of transcription of several cell wall–related genes was analyzed using RT-qPCR. These results lead us to a comprehensive picture of the cell wall, the importance of the various components and how the fungus copes with changes in it cell wall. The results can then be used to identify antifungal drugs for novel targets in the cell wall and combinatorial treatment strategies that can subvert the compensatory mechanisms used the maintain cell wall integrity.

3 / Talaromyces marneffei cell wall glucans: their role in recognition by host cell and pathogenicity