Project description:Tigecycline, a protein translation inhibitor, is a treatment of last resort for infections caused by the opportunistic multidrug resistant human pathogen Acinetobacter baumannii. However, strains resistant to tigecycline were reported not long after its clinical introduction. Translation inhibitor antibiotics perturb ribosome function and induce the reduction of (p)ppGpp, an alarmone involved in the stringent response that negatively modulates ribosome production. Through RNA sequencing, this study revealed a significant reduction in the transcription of genes in citric acid cycle and cell respiration, suggesting tigecycline inhibits or slows down bacterial growth. Our results indicated that the drug-induced reduction of (p)ppGpp level promoted the production but diminished the degradation of ribosomes, which mitigates the translational inhibition effect by tigecycline. The reduction of (p)ppGpp also led to a decrease of transcription coupled nucleotide excision repair which likely increases the chances of development of tigecycline resistant mutants. Increased expression of genes linked to horizontal gene transfer were also observed. The most upregulated gene, rtcB, involving in RNA repair, is either a direct tigecycline stress response or is in response to the transcription de-repression of a toxin-antitoxin system. The most down-regulated genes encode two b-lactamases, which is a possible by-product of tigecycline-induced reduction in transcription of genes associated with peptidoglycan biogenesis. This transcriptomics study provides a global genetic view of why A. baumannii is able to rapidly develop tigecycline resistance.
Project description:The antibiotic resistance of A. baumannii has been increasing in recent years. There are still many questions unclear concerning the mechanism of tigecycline resistance in A. baumannii. iTRAQ based proteomic analysis were used to reveal the mechanism of tigecycline resistance in Acinetobacter baumannii.
Project description:The mechanism of tigecycline resistance in Acinetobacter baumannii under sub-minimal inhibitory concentration tigecycline by comparative protemics
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:Acinetobacter baumannii AB042, a triclosan-resistant mutant, was examined for modulated gene expression using whole genome sequencing, transcriptomics, and proteomics in order to understand the mechanism of triclosan-resistance as well as its impact on A. Baumannii.
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: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.
