Proteomics of Rat Lungs Infected by Cryptococcus gattii Reveals a Potential Warburg-like Effect

Cryptococcus gattii is the causative
agent of cryptococcosis infection that can lead to pneumonia and meningitis
in immunocompetent individuals. The molecular basis of the pathogenic
process and impact on the host biochemistry are poorly understood
and remain largely unknown. In this context, a comparative proteomic
analysis was performed to investigate the response of the host during
an infection caused by C. gattii. Lungs
of experimentally infected rats were analyzed by shotgun proteomics
to identify differentially expressed proteins induced by C. gattii clinical strain. The proteomic results
were characterized using bioinformatic tools, and subsequently, the
molecular findings were validated in cell culture and lungs of infected
animals. A dramatic change was observed in protein expression triggered
by C. gattii infection, especially
related to energy metabolism. The main pathways affected include aerobic
glycolysis cycle, TCA cycle, and pyrimidine and purine metabolism.
Analyses in human lung fibroblast cells confirmed the altered metabolic
status found in infected lungs. Thus, it is clear that C. gattii infection triggers important changes in
energy metabolism leading to the activation of glycolysis and lactate
accumulation in lung cells, culminating in a cancerlike metabolic
status known as the Warburg effect. The results presented here provide
important insights to better understand C. gattii molecular pathogenesis.