ABSTRACT: Metagenomics analysis revealing the characterization of antibiotic resistance genes and their relationship with the pathogen in aquaculture ponds
Project description:Infectious pancreatic necrosis (IPN) is a serious viral disease that causes significant economic losses in salmon aquaculture. To characterize the host-pathogen relationship in IPN, we analysed transcriptional profiles of salmon head kidney (SHK-1) cells infected with infectious pancreatic necrosis virus (IPNV) at three timepoints over six days (at 1, 3 & 6 days post infection. The transcriptome was investigated using the TRAITS / SGP 16950-feature Atlantic salmon cDNA microarray, which is enriched for genes with functions related to the immune response.
Project description:With the global increase in the use of carbapenems, several gram-negative bacteria have acquired carbapenem resistance, thereby limiting treatment options. Klebsiella pneumoniae is one of such notorious pathogen that is being widely studied to find novel resistance mechanisms and drug targets. These antibiotic-resistant clinical isolates generally harbor many genetic alterations, and identification of causal mutations will provide insights into the molecular mechanisms of antibiotic resistance. We propose a method to prioritize mutated genes responsible for antibiotic resistance, in which mutated genes that also show significant expression changes among their functionally coupled genes become more likely candidates. For network-based analyses, we developed a genome-scale co-functional network of K. pneumoniae genes, KlebNet (www.inetbio.org/klebnet). Using KlebNet, we could reconstruct functional modules for antibiotic-resistance, and virulence, and retrieved functional association between them. With complementation assays with top candidate genes, we could validate a gene for negative regulation of meropenem resistance and four genes for positive regulation of virulence in Galleria mellonella larvae. Therefore, our study demonstrated the feasibility of network-based identification of genes required for antimicrobial resistance and virulence of human pathogenic bacteria with genomic and transcriptomic profiles from antibiotic-resistant clinical isolates.
Project description:<p>Aeromonas veronii (A. veronii) is a zoonotic pathogen. It causes clinically a variety of diseases such as dysentery, bacteremia, and meningitis. And it also brings huge losses to aquaculture. A. veronii has been documented as a multiple antibiotic resistant bacterium. Hfq (host factor for RNA bacteriophage Qβ replication) plays vital regulation roles in a variety of cell programs. The deletion of hfq in A. veronii showed an increased sensitivity to the trimethoprim, accompanying by the down regulation of the efflux pump related genes acrA and acrB in transcriptomic data. Coherently, the complementation of acrA and acrB in ∆hfq recovered the trimethoprim resistance. Besides, the productions of adenosine and guanosine were revealed to augment in ∆hfq in metabonomic data. Both wild type and ∆hfq conferred more sensitive to trimethoprim after appending 1 mM adenosine or guanosine to M9 medium. These results demonstrated that Hfq mediated trimethoprim resistance by elevating efflux pump expression and degrading adenosine, and guanosine metabolites. Collectively, Hfq is a potential target to tackle trimethoprim resistance in A. veronii infection.</p>
