XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:96-2

Investigação

96-2	PRP8 INTEIN: A PARASITIC GENETIC ELEMENT IN A HOUSE KEEPING GENE OF Paracoccidioides brasiliensis- MEANING AND APPLICATIONS
Authors:	Raquel Cordeiro Theodoro (UNESP - Universidade Estadual Paulista Júlio de Mesquita Filho) ; Eduardo Bagagli (UNESP - Universidade Estadual Paulista Júlio de Mesquita Filho)

Abstract

Inteins are intervening sequences translated in frame with the host protein coding gene. They are self-excised through protein splicing, joining the N and C terminals of the host protein by a peptide bond, maintaining its normal function. Besides their splicing domain, inteins might also contain a homing endonuclease (HE) domain, making them mobile elements. Inteins are also considered promising therapeutic drug target, since once the autocatalytic splicing is inhibited, the host protein, which is typically vital, will not be able to perform its normal function and the fungal cell will not survive or reproduce.਀吀栀攀倀刀倀㠀椀渀琀攀椀渀漀挀挀甀爀猀椀渀琀栀攀倀爀瀀㠀瀀爀漀琀攀椀渀Ⰰ 愀挀漀洀瀀漀渀攀渀琀漀昀唀㔀猀渀刀一倀猀椀洀瀀氀椀挀愀琀攀搀椀渀琀栀攀攀搀椀琀椀渀最漀昀瀀爀攀ⴀ洀攀猀猀攀渀最攀爀刀一䄀猀⸀ 吀栀椀猀椀渀琀攀椀渀栀愀猀戀攀攀渀昀漀甀渀搀椀渀椀洀瀀漀爀琀愀渀琀栀甀洀愀渀瀀愀琀栀漀最攀渀猀昀爀漀洀㰀椀㸀䌀爀礀瀀琀漀挀漀挀挀甀猀㰀⼀椀㸀愀渀搀㰀椀㸀䄀猀瀀攀爀最椀氀氀甀猀㰀⼀椀㸀最攀渀攀爀愀愀渀搀愀氀猀漀昀爀漀洀䄀樀攀氀氀漀洀礀挀攀琀愀挀攀愀攀昀愀洀椀氀礀Ⰰ 猀甀挀栀愀猀㰀椀㸀䠀椀猀琀漀瀀氀愀猀洀愀挀愀瀀猀甀氀愀琀甀洀㰀⼀椀㸀Ⰰ 㰀椀㸀䈀氀愀猀琀漀洀礀挀攀猀搀攀爀洀愀琀椀琀椀搀椀猀㰀⼀椀㸀Ⰰ 㰀椀㸀䔀洀洀漀渀猀椀愀瀀愀爀瘀愀㰀⼀椀㸀愀渀搀倀愀爀愀挀漀挀挀椀搀椀漀椀搀攀猀猀瀀攀挀椀攀猀⸀ The phylogenetic potential of this region was studied in order to distinguish the four cryptic species of Paracoccidioides genus (S1, PS2 and PS3, from the P. brasiliensis complex, and P. lutzii). Maximum-Parsimony, Maximum Likelihood, and Bayesian analysis clearly separated the isolates from the three species and revealed a significant divergence between the Pb01 isolate, from P. lutzii species, and the remaining ones.਀吀栀攀猀瀀氀椀挀椀渀最昀甀渀挀琀椀漀渀漀昀琀栀攀倀倀刀㠀椀渀琀攀椀渀猀昀爀漀洀䈀⸀ 搀攀爀洀愀琀椀琀椀搀椀猀Ⰰ 䔀⸀ 瀀愀爀瘀愀愀渀搀昀漀甀爀挀爀礀瀀琀椀挀猀瀀攀挀椀攀猀漀昀㰀椀㸀倀⸀ 戀爀愀猀椀氀椀攀渀猀椀猀㰀⼀椀㸀眀愀猀攀瘀愀氀甀愀琀攀搀椀渀愀渀漀渀ⴀ渀愀琀椀瘀攀爀攀挀漀洀戀椀渀愀渀琀瀀爀漀琀攀椀渀挀漀渀琀攀砀琀戀礀椀渀猀攀爀琀椀渀最琀栀攀椀渀琀攀椀渀戀攀琀眀攀攀渀愀䴀愀氀琀漀猀攀䈀椀渀搀椀渀最倀爀漀琀攀椀渀愀渀搀愀吀栀椀漀爀攀漀搀漀砀椀渀Ⰰ 椀渀㰀椀㸀䔀猀挀栀攀爀椀挀栀椀愀挀漀氀椀㰀⼀椀㸀挀攀氀氀猀⸀ 䄀氀氀倀刀倀㠀椀渀琀攀椀渀猀瀀爀漀瘀攀搀琀漀戀攀愀挀琀椀瘀攀椀渀琀栀椀猀攀砀琀攀椀渀洀漀搀攀氀Ⰰ 猀甀最最攀猀琀椀渀最琀栀攀椀爀甀猀攀昀甀氀渀攀猀猀昀漀爀猀挀爀攀攀渀椀渀最搀爀甀最猀琀栀愀琀椀渀栀椀戀椀琀琀栀攀椀渀琀攀椀渀攀砀挀椀猀椀漀渀椀渀瀀愀琀栀漀最攀渀猀昀爀漀洀琀栀攀䄀樀攀氀氀漀洀礀挀攀琀愀挀攀愀攀昀愀洀椀氀礀⸀ In silico and in vitro experimental analyses of HE domain provide evolutionary evidence that the P. brasiliensis PRP8 intein lost its endonuclease activity, revealing that this domain was active until recently but it is now in a degenerative process. ਀䘀椀渀愀渀挀椀愀氀匀甀瀀瀀漀爀琀㨀䘀愀瀀攀猀瀀㈀　　㜀⼀　㄀㌀　㘀ⴀ㔀愀渀搀㈀　㄀　⼀　㠀㠀㈀㤀ⴀ㘀⸀

Keyword: Ajellomycetaceae, cryptic species, endonuclease domain, splicing domain, therapeutic target

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