GSE194255
Transcriptomics analysis reveals the molecular mechanisms of the  antibacterial activity of gallium nitrate against Acinetobacter baumannii isolated from bloodstream infections
Purpose: The aim of this study was to explore the antibacterial effect and molecular mechanism  of gallium nitrate [Ga(NO 3 ) 3 ] against Acinetobacter baumannii from bloodstream  infection. Methods: A total of 40 A. baumannii with different antimicrobials susceptibility patterns were isolated from bloodstream infections. In vitro antibacterial effect of Ga(NO 3 ) 3 was analyzed by micro-dilution method and time-kill assay. The effect of ferric chloride/heme on the antibacterial effect of Ga(NO 3 ) 3 was evaluated.  Transcriptome sequencing was performed to elucidate the antibacterial mechanism of gallium nitrate. Mouse infection model was conducted to explore the in vivo efficacy of gallium nitrate . Results: Ga(NO 3 ) 3 exhibited excellent antibacterial effect in RPMI 1 640 medium containing 10% human serum (MICs ranged from 0.06 µg/mL to 0.125 µg/mL),  whereas its antibacterial effect was weakened by exogenous ferric chloride/heme.  Ga(NO 3 ) 3 inhibited A. baumannii growth in a dose- and time- dependent manner.  Ga(NO 3 ) 3 exerted antibacterial effect by up-regulating the expression of genes associated with biosynthesis and transport of siderophore and disrupting multiple iron  dependent metabolism processes. Ga(NO 3 ) 3 significantly reduced bacterial load in the neutropenic mouse thigh infection model. Conclusions: This study revealed that Ga(NO 3 ) 3 had excellent antibacterial activity both in vivo and in vitro . It might be a potential drug for treating bloodstream infections of A. baumannii Overall design: mRNA profiles of A. baumannii BM2333 wildtype and Ga(NO3 )3-treated BM2333