Abstract

Introduction: The dimorphic fungus Paracoccidioides brasiliensis is the causative agent of the most frequent systemic mycosis in Latin America. In humans, infection starts by inhalation of fungal propagules, which reach the pulmonary epithelium and differentiate into the yeast parasitic phase. Infectious diseases are the result of a close relationship between the pathogen and its host and the knowledge of this complex interaction is essential for advancing the understanding of the mechanisms of infection establishment. Studies from our laboratory allowed the suggestion of some adaptation strategies of P. brasiliensis during the infective process indicating differential regulation on niche dependence. The integration of proteomics and transcriptomics can aid the understanding of regulatory mechanisms and central metabolic pathways during the infection process and in different niches of infection in the host. Objective: identification of genes and proteins of P. brasiliensis induced during the infection process in the lung. Methods: Female Balb/C mice were infected intranasally with 1 x 107 yeast cells and killed on the 7th and 15th days after infection; lungs were removed homogenized and plated. After 14 days of plating, the yeast cells were used to extract total RNA. The Representational Difference Analysis (cDNA-RDA) was used to identify P. brasiliensis genes induced during the infective process. Results: This work describes the analysis of differentially expressed genes in yeast cells of P. brasiliensis recovered from the lungs of infected animals after 7 and 15 days of infection in relation to the fungus in culture maintained in laboratory. The data revealed that genes related to fatty acid degradation, protein synthesis, osmotic stress, cell wall remodeling and cell defense were induced in yeast cells derived from infected lung. The data were confirmed in yeast cells infecting lungs. Conclusions: The data suggest metabolic pathways induced during infection in the lung which may be important strategies for survival and growth of P. brasiliensis in different niches of the host. Proteomics analyses are under progress.਀䘀椀渀愀渀挀椀愀氀 匀甀瀀瀀漀爀琀㨀 䌀一倀焀Ⰰ 䘀䤀一䔀倀Ⰰ 䌀䄀倀䔀匀㰀⼀昀漀渀琀㸀㰀⼀瀀㸀㰀戀爀㸀㰀戀㸀䬀攀礀眀漀爀搀㨀 㰀⼀戀㸀☀渀戀猀瀀㬀刀攀瀀爀攀猀攀渀琀愀琀椀漀渀愀氀 䐀椀昀昀攀爀攀渀挀攀 䄀渀愀氀礀猀椀猀Ⰰ 氀甀渀最 椀渀昀攀挀琀椀漀渀Ⰰ 栀漀猀琀ⴀ昀甀渀最甀猀 椀渀琀攀爀愀挀琀椀漀渀㰀⼀琀搀㸀㰀⼀琀爀㸀㰀⼀琀愀戀氀攀㸀㰀⼀琀爀㸀㰀⼀琀搀㸀㰀⼀琀愀戀氀攀㸀㰀⼀戀漀搀礀㸀㰀⼀栀琀洀氀㸀