Project description:Acinetobacter baumannii is a Gram-negative pathogen that has emerged as one of the most troublesome pathogens for health care institutions globally. Bacterial quorum sensing (QS) is a process of cell-to-cell communication that relies on the production, secretion and detection of autoinducer (AI) signals to share information about cell density and regulate gene expression accordingly. The molecular and genetic basis of Acinetobacter baumannii virulence remains poorly understood. Therefore, the contribution of the abaI/abaR quorum sensing system to growth characteristics, morphology, biofilm formation, resistance, motility and virulence of Acinetobacter baumannii was studied in detail. RNA-seq analysis indicated that genes involved in various aspects of energy production and conversion, Valine, leucine and isoleucine degradation and lipid transport and metabolism are associated with bacterial pathogenicity. Our work provides a new insight into abaI/abaR quorum sensing system effects pathogenicity in A. baumannii. We propose that targeting the AHL synthase enzyme abaI could provide an effective strategy for attenuating virulence. On the contrary, interdicting the autoinducer synthase–receptor abaR elicits unpredictable consequences, which may lead to enhanced bacterial virulence.
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: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:In recent years, the Gram-negative bacterium Acinetobacter baumannii has garnered considerable attention for its unprecedented capacity to rapidly develop resistance to antibacterial therapeutics. This is coupled with the seemingly epidemic emergence of new hyper-virulent strains. Although strain-specific differences for A. baumannii isolates have been well described, these studies have primarily focused on proteinaceous factors. At present, only limited publications have investigated the presence and role of small regulatory RNA (sRNA) transcripts. Herein, we perform such an analysis, describing the RNA-seq-based identification of 78 A. baumannii sRNAs in the AB5075 background. Together with six previously identified elements, we include each of these in a new genome annotation file, which will serve as a tool to investigate regulatory events in this organism. Our work reveals that the sRNAs display high expression, accounting for >50 % of the 20 most strongly expressed genes. Through conservation analysis we identified six classes of similar sRNAs, with one found to be particularly abundant and homologous to regulatory, C4 antisense RNAs found in bacteriophages. These elements appear to be processed from larger transcripts in an analogous manner to the phage C4 molecule and are putatively controlled by two further sRNAs that are strongly antisense to them. Collectively, this study offers a detailed view of the sRNA content of A. baumannii, exposing sequence and structural conservation amongst these elements, and provides novel insight into the potential evolution, and role, of these understudied regulatory molecules. This study is based on the annotation of novel sRNAs on basis of an Acinetobacter baumannii RNA sequencing dataset. Each sample was generated by pooling three independent biological replicate RNA preps