Project description: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
Project description:In the present work we compare the gene expression profile of A. baumannii and a mutant knock-out strain of A. baumannii lacking a small RNA gene 13573 and the corresponding small RNA 13573 over-producing strain. The main objective is to recognize the main pathways in which the small RNA 13573 is involved. Moreover, the same wild type strain was used to infect mice and was further analyzed after the infection with the aim of finding genes differentially expressed in vivo. Three biological replicates have been performed for each comparison. The RNA collection from Acinetobacter baumannii strain over-expresing the small RNA (sample 13573) was compared with this isolated from A. baumannii harboring the empty vector (PETRA sample) while gene expression in the knock-out strain (KO sample) was compared with the wild type strain Acinetobacter baumannii ATCC 17978 (ATCC sample). The RNA from A.baumannii recovered from the infected animals (INF sample) was compared with the wild type (ATCC).
Project description:Acinetobacter baumannii is an important pathogen of nosocomial infection worldwide, which can primarily cause pneumonia, bloodstream infection, and urinary tract infection. The increasing drug resistance rate of A. baumannii and the slow development of new antibacterial drugs brought great challenges for clinical treatment. Host immunity is crucial to the defense of A. baumannii infection, and understanding the mechanisms of immune response can facilitate the development of new therapeutic strategies. To obtain the system-level changes of host proteome in immune response, we used TMT labeling quantitative proteomics to compare the proteome changes of lungs from A. baumannii infected mice with control mice six hours after infection. A total of 6218 proteins were identified in which 6172 could be quantified. With threshold p < 0.05 and fold change > 1.2, we found 120 differentially expressed proteins. Bioinformatics analysis showed that differentially expressed proteins after infection were associated with receptor recognition, NADPH oxidase (NOX) activation and antimicrobial peptides. These differentially expressed proteins were involved in the pathways including leukocyte transendothelial migration, phagocyte, neutrophil degranulation, and antimicrobial peptides. In conclusion, our study showed proteome changes in mouse lung tissue due to A. baumannii infection and suggested the important roles of NOX, neutrophils, and antimicrobial peptides in host response. Our results provide a potential list of proteins candidates for the further study of host-bacteria interaction in A. baumannii infection.
Project description:Using Nanopore sequencing, our study has revealed a close correlation between genomic methylation levels and antibiotic resistance rates in Acinetobacter Baumannii. Specifically, the combined genome-wide DNA methylome and transcriptome analysis revealed the first epigenetic-based antibiotic-resistance mechanism in A. baumannii. Our findings suggest that the precise location of methylation sites along the chromosome could provide new diagnostic markers and drug targets to improve the management of multidrug-resistant A. baumannii infections.
Project description:Two Acinetobacter baumannii strains with low susceptibility to fosmidomycin and two reference with high susceptibility to fosmidomycin were DNA-sequenced to investigate the genomic determinants of fosmidomycin resistance.
Project description:Acinetobacter baumannii causes high mortality in ventilator-associated pneumonia patients and antibiotic treatment is compromised in multi-drug resistant strains resistant to beta-lactams, carbapenems, cephalosporins, polymyxins and tetracyclines. Among COVID-19 patients receiving ventilator support, multi-drug resistant A. baumannii secondary infection is associated with a two-fold increase in mortality. Here we investigated the use of the 8-hydroxyquinoline ionophore PBT2 to break resistance of A. baumannii to tetracycline class antibiotics.
