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:Coordinated protein-coding sequence transcriptional responses of Staphylococcus aureus to antimicrobial exposure are well described but little is known of the role of bacterial non-coding, small RNAs (sRNAs) in these responses. Here we used RNAseq to investigate the sRNA response of the epidemic multiresistant hospital ST239 S. Aureus strain JKD6009 and its vancomycin-intermediate clinical derivative, JKD6008, after exposure to four antibiotics representing the major classes of antimicrobials used to treat methicillin-resistant S. Aureus infections. These agents included vancomycin, linezolid, ceftobiprole, and tigecycline. We identified 410 potential sRNAs (sRNAs) and then compared global sRNA and mRNA expression profiles at 2 and 6 hours, without antibiotic exposure, and after exposure to 0.5 x MIC for each antibiotic, for both JKD6009 (VSSA), and JKD6008 (VISA). Two strains were used (JKD6009, vancomycin-susceptible S. Aureus; JKD6008, in vivo derived vancomycin-intermediate S. Aureus). The complete JKD6008 genome seqeuce was used as the reference. Two time points, 2 hours and 6 hours after culture in Mueller Hinton broth. Strains were exposed to no antibiotic, or 0.5 x MIC for 10 mins for the following antibiotics; vancomycin, linezolid, ceftobiprole, tigecycline. RNA isolation procedures enriched for mRNA or sRNA. The 40 cDNA libraries were sequenced using a whole flowcell (8 lanes) in an Illumina genome analyzer GAII for 36 cycles. Data was analyzed using the BioConductor package limma, and by applying non-negative matrix factorization to determine the impact of antibiotic exposure on the sRNA and mRNA transcriptional profiles.
Project description:Purpose: The present study provides the firstly large-scale characterization of miRNAs in Tetranychus cinnabarinus and the comparison between fenpropathrin resistant and susceptible strains gives a clue on study how miRNA involving in fenpropathrin resistance Methods: Using Illumina sequencing to identify the differentially expressed miRNAs between the fenpropathrin resistant and susceptible strains of Tetranychus cinnabarinus Results: 12 miRNAs that were expressed significantly differently were identified between thethe fenpropathrin resistant and susceptible strains of Tetranychus cinnabarinus
Project description:Analysis of pulmonary gene expression in two mouse strains, resistant (BALB/c) and susceptible (CBA/Ca) to Streptococcus pneumoniae infection. Data collected at 6h post-infection and for control animals (PBS-treated). The list of differentially expressed genes was created by comparisons of infected versus PBS-treated animals and PBS-treated BALB/c versus CBA/Ca. The hypothesis tested in the present study was that pulmonary transcriptomes of both mouse strains differ during pneumococcal infection and in non-disease conditions. Results provided important information on differences in immune responses between both mouse strains. The results identified genes and pathways uniquely regulated by only one of the tested mouse strains helping to understand molecular mechanism behind resistance or susceptibility to pneumococcal infections. Total RNA obtained from lung tissue from BALB/cOlaHsd and CBA/CaOlaHsd mouse strains (Harlan) 6 hours post intranasal infection with Streptococcus pneumoniae serotype 2 strain D39 dose 5.0E06 or PBS-treated animals