Divergent Targets of XXXX AcuK and AcuM Transcription Factors during Growth in vitro versus Invasive Disease.

@entity19 @entity14940 @entity54 @entity358 @entity68 @entity59531
UNASSIGNED: In @entity14940 , the AcuK and AcuM transcription factors form a complex that regulates gluconeogenesis. In @entity54 , AcuM governs gluconeogenesis and @entity68 acquisition in vitro, and virulence in immunosuppressed @entity19 . However, the function of AcuK was previously unknown. Through in vitro studies, we found that A. fumigatus   acuK single and   acuK   acuM double mutants had impaired gluconeogenesis and @entity68 acquisition, similar to the   acuM mutant. Also, the   acuK,   acuM, and   acuK   acuM mutants had similar virulence defects in @entity19 . However, compared to the   acuM mutant, the   acuK mutant had a milder defect in extracellular siderophore activity and induction of epithelial cell damage in vitro. Moreover, overexpression of acuM in the   acuK mutant altered expression of 3 genes and partially restored growth under @entity68 -limited conditions, suggesting that AcuM can govern some genes independently of AcuK. Although the   acuK and   acuM mutants had very similar transcriptional profiles in vitro, their transcriptional profiles during @entity19 @entity358 differed both from their in vitro profiles and from each other. While AcuK and AcuM governed the expression of only a few @entity68 responsive genes in vivo, they influenced the expression of other virulence-related genes such as @entity59531 and dvrA. Therefore, in A. fumigatus, while AcuK and AcuM likely function as part of the same complex, they can also function independently of each other. Furthermore, AcuK and AcuM have different target genes in vivo as compared to in vitro, suggesting that in vivo infection stimulates unique transcriptional regulatory pathways in A. fumigatus.
