ERG11 mutations and expression of resistance genes in XXXX -resistant @entity5132 isolates.

@entity72172 @entity2380 @entity5132 @entity72171 @entity72174 @entity375 @entity5638 @entity72173
UNASSIGNED: @entity5638 resistance in the pathogenic @entity375 @entity5132 poses significant challenges for its antibiotic treatment. The conformational change of the target enzyme 14 alpha-demethylase (Erg11p) due to ERG11 gene mutations is one of the mechanisms resulting in the @entity5638 resistance. ERG11 of 23 isolates (8 susceptible and 15 resistant) and 6 standard strains of @entity5132 were amplified and sequenced. Nineteen missense mutations were detected. Two mutations, @entity72171 ( @entity72172 ) and @entity72173 ( @entity72174 ), coexisted exclusively in 14 @entity2380 -resistant isolates. To identify the resistance mechanisms in the isolates with @entity72171 and @entity72173 mutations, we compared the expression of 5 resistance-related genes in the 14 @entity5638 -resistant isolates with those in the susceptible type strain ATCC 10231, @entity375 AD/CDR1 and AD/CDR2. The tested values of mRNA transcription of CDR1 and CDR2 were higher than that of control strain, while the semi-quantified Cdr1p values were not higher in all of the 14 resistant isolates. And the data analyzed with t test suggest that both of the differences are significant (P  <  0.0005) when the resistant isolates are considered as a whole. Cdr2p was up-regulated in 5 isolates, and down-regulated or even undetectable in the remaining 9 isolates. The transcription of ERG11, MDR1, and FLU1 varied in these isolates. These data suggested that overexpression of the five genes might not be the reason of resistance in the 14 isolates with @entity72171 and @entity72173 , especially in the 5 isolates (GZ09, GZ15, GZ16, GZ58, and 4263) in which neither translation of Cdr1p/Cdr2p nor transcription of ERG11, MDR1, or FLU1 was detected up-regulated. The results suggest that Erg11p conformational change due to the point mutations is most likely responsible for the @entity5638 resistance in these isolates.
