Project description:Objectives: Colistin remains a last-line treatment for multidrug-resistant Acinetobacter baumannii and combined use of colistin and carbapenems has shown synergistic effects against multidrug-resistant strains. In order to understand the bacterial responses to these antibiotics we analysed the transcriptome of A. baumannii following exposure to each.
Project description:Here we investigated colistin effects on A. baumannii, employing a Mass spectrometry approach and comparing a colistin-susceptible multidrug-resistantclinical isolate to its colistin-dependent subpopulation obtained by subsequent passages in moderate colistin concentrations. Colistin dependence might represent a stepping-stone to resistance, but the mechanisms of colistin dependence are far from clear.
Project description:We analyzed the extracellular proteome of colistin-resistant Korean Acinetobacter baumannii (KAB) strains to identify proteome profiles that can be used to characterize extensively drug-resistant KAB strains.
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:Colistin is a crucial last-line drug used for the treatment of life-threatening infections caused by multi-drug resistant strains of the Gram-negative bacteria, Acinetobacter baumannii. However, colistin resistant A. baumannii isolates can be isolated following failed colistin therapy. Resistance is most often mediated by the addition of phosphoethanolamine (pEtN) to lipid A by PmrC, following missense mutations in the pmrCAB operon encoding PmrC and the two-component signal transduction system PmrA/PmrB. We recovered an isogenic pair of A. baumannii isolates from a single patient before (6009-1) and after (6009-2) failed colistin treatment that displayed low/intermediate and high levels of colistin resistance, respectively. To understand how increased colistin-resistance arose, we genome sequenced each isolate which revealed that 6009-2 had an extra copy of the insertion sequence element ISAba125 within a gene encoding an H-NS-family transcriptional regulator. Consequently, transcriptomic analysis of the clinical isolates identified was performed and more than 150 genes as differentially expressed in the colistin-resistant, hns mutant, 6009-2. Importantly, the expression of eptA, encoding a second lipid A-specific pEtN transferase, but not pmrC, was significantly increased in the hns mutant. This is the first time an H-NS-family transcriptional regulator has been associated with a pEtN transferase and colistin resistance.
Project description:Acinetobacter baumannii is a major cause of nosocomial infections which can survive in different hospital environments and its multidrug-resistant capacity is major concern now-a-days. ppGpp dependent stringent response mediates reprogramming of gene expression with diverse function in many bacteria. A baumannii A1S_0579 gene is responsible for ppGpp production. Transcriptome analysis of early stationary phase cultures represents several differentially expressed genes in ppGpp deficient strain (∆A1S_0579). We found that the expression of csu operon, which is important in pili biosynthesis for early biofilm formation, was significantly reduced in the ppGpp-deficient strain. Our findings showed that ppGpp signaling plays critical role in biofilm formation, surface motility, adherence and virulence of A baumannii. This study is the first demonstration of the association between ppGpp and pathogenicity of A. baumannii.
