Caracterização dos mecanismos de captação de ferro em Fonsecaea pedrosoi e Cladophialophora carrionii
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Data
2017-02-20
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Universidade Federal de Goiás
Resumo
The polymorphic fungi Fonsecaea pedrosoi and Cladophialophora carrionii are the
main etiological agents of Chromoblastomycosis (CBM), a chronic cutaneous mycotic
infection, which occurs mainly in humid tropical regions. The scarcity of effective therapeutic
protocols added to the clinical polymorphism of CBM leads to prolonged therapies and a high
relapse rate. There are few data on the molecular biology of F. pedrosoi and C. carrionii,
although some virulence factors have already been described, revealing the need to explore
the mechanisms used by these pathogens during infection. Iron is a vital micronutrient for all
organisms, with the exception of some bacteria, participating in essential cellular processes,
such as: DNA replication, oxidative stress, cellular respiration, oxygen transport, energy
production, among others. During the infection, the host decreases the availability of iron to
the pathogen to contain the advancement of the infection; while the pathogen activates
mechanisms for obtain and use the metal to survive in the infected tissues, revealing a
scenario of intense dispute. In order to characterize the presence of these systems in F.
pedrosoi and C. carrionii, in sílico analyzes were performed, revealing the presence of
orthologs for proteins involved in reductive iron assimilation, siderophore mediated uptake
and regulators of capture and utilization strategies of the metal, these sequences containing
conserved domains consistent with the predicted functions. The expression profile of
transcripts demonstrated the induction of iron reducing scavengers, siderophore biosynthesis
intermediates and the hapX positive regulator during iron deprivation, in addition to
repressing the negative regulatory sreA. The production of siderophores was observed after
qualitative approaches, and the siderophore ferricrocine was subsequently identified intra- and
extracellularly in F. pedrosoi and C. carrionii. These siderophores were able to restore the
growth of a mutant strain of ΔsidA from A. nidulans. Preferred iron sources were observed
after growth assays and, in addition, some of these sources were used by F. pedrosoi and C.
carrionii during infection in macrophages, demonstrating that these pathogens may have
strategies for remodeling iron homeostasis for survival.
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Palavras-chave
Virulência , Sideróforos , Metal , Via redutiva , Reguladores , Virulence , Siderophores , Metal , Reductive pathway , Regulators
Citação
SILVA, K. L. P. Caracterização dos mecanismos de captação de ferro em Fonsecaea pedrosoi e Cladophialophora carrionii. 2017. 99 f. Dissertação (Mestrado em Genética e Biologia Molecular) - Universidade Federal de Goiás, Goiânia, 2017.