Discussion

Leishmania communicate with their host environments by the uptake and secretion of proteins and metabolites. Secreted molecules from the parasite are hypothesised to play a critical role in parasite establishment and survival through amelioration of host challenges or augmentation of nutrient availability. Our aim is to identify effector molecules and survival mechanisms used by the parasite to maintain infection. We have optimised methods of controlled serum-free secretome extraction to minimise the contribution of serum and cell lysis proteins to the proteome of the cell conditioned media. Results show the identification of proteins enriched in the secretome of both promastigotes and amastigotes of L. mexicana. In addition, differences between the secreted proteins of the two forms are highlighted, indicating a defined role for these secreted proteins in each of the distinct host environments. Furthermore, attenuated parasites which can infect but do not survive in macrophages demonstrate significant differences in their secreted proteins to that of the wild type. This indicates a key role for secreted proteins in parasite survival in the host cell. Investigating the host parasite interaction furthers our understanding of the factors that determine the growth and persistence of these parasites in the body to aid in the development of drug interventions.