Project description:PoxtA and OptrA are ATP binding cassette (ABC) proteins of the F subtype (ABCF) that confer resistance to oxazolidinone, such as linezolid, and phenicol antibiotics, such as chloramphenicol. PoxtA/OptrA are often encoded on mobile genetic elements, facilitating their rapid spread amongst Gram-positive bacteria. These target protection proteins are thought to confer resistance by binding to the ribosome and dislodging the antibiotics from their binding sites. However, a structural basis for their mechanism of action has been lacking. Here by investigating 5'P mRNA decay intermediates, that provide ribosome protection data, we show that PoxtA protects against Linezolid specific stalls. Furthermore, we present cryo-electron microscopy structures of PoxtA in complex with the Enterococcus faecalis 70S ribosome at 2.9–3.1 Å, as well as the complete E. faecalis 70S ribosome at 2.2–2.5 Å. The structures reveal that PoxtA binds within the ribosomal E-site with its antibiotic resistance domain (ARD) extending towards the peptidyltransferase center (PTC) on the large ribosomal subunit. At its closest point, the ARD of PoxtA is still located >15 Å from the linezolid and chloramphenicol binding sites, suggesting that drug release is elicited indirectly. Instead, we observe that the ARD of PoxtA perturbs the CCA-end of the P-site tRNA causing it to shift by ~4 Å out of the PTC, which correlates with a register shift of one amino acid for the attached nascent polypeptide chain. Given that linezolid and chloramphenicol are context-specific translation elongation inhibitors, we postulate that PoxtA/OptrA confer resistance to oxazolidinones and phenicols indirectly by perturbing the P-site tRNA and thereby altering the conformation of the attached nascent chain to disrupt the drug binding site.
Project description:To explore whether KSHV infection is a risk factor for osteosarcoma development in ethnic Uyghur population. Sarcoma specimens including tumor, adjacent normal tissues and paired blood samples were obtained from several osteosarcoma patients of Xinjiang China. Then, osteosarcoma clinical samples were subjected to analysis for the presence of the KSHV genome and proteins. Gene expression profiles of these osteosarcomas were analyzed to reveal the pathogenesis of KSHV-positive and -negative osteosarcomas.
2019-09-01 | GSE126209 | GEO
Project description:cfr and optrA-positive Staphylococcus spp.
Project description:Enterocin AS-48 is produced by Enterococcus faecalis S48 to compete with other bacteria in their environment. Due to its activity against various Gram positive and some Gram negative bacteria it has clear potential for use as a food preservative. Here, we studied the effect of enterocin AS-48 challenges on vegetative cells of Bacillus cereus ATCC 14579 by use of transcriptome analysis.
Project description:To study the role of miRNAs in the transition from latent to active TB and to discover candidate biomarkers that may help predict TB progression, we have employed miRNA microarray expression profiling as a discovery platform to probe the transcriptome of peripheral blood mononuclear cells (PBMCs) with active TB, latent TB infection (LTBI), and healthy donors.Patients were recruited at the Shanghai Public Health Clinical Centre (Shanghai, China) from December, 2008 to May, 2009. The diagnosis of active TB was based on clinical presentation, chest radiography, and acid-fast stain of sputum smear.All the patients were HIV negative, as diagnosed by the Livzon Anti-HIV1/2 EIA Kit (Livzon Pharmaceutical Group Inc., Guangdong, China). Additional tests were also performed to detect hepatitis B virus (HBV) and hepatitis C virus (HCV) by using the Abbott AxSYM anti-HBsAg and HCV 3.0 antibody assay kit (Abbott Laboratories, Illinois) to exclude HBV- and HCV-positive patients (these 2 diseases are highly prevalent in China). Patients with a diabetes history were also excluded because diabetes could increase the risk of TB. Peripheral venous blood was drawn before treatment. Subjects with LTBI and healthy donors both without a history of clinical TB or other infectious diseases were recruited from the staff at the Shanghai Public Health Clinical Centre. TST and IGRA (T-SPOT®.TB, Oxford Immunuotec, Oxfordshire, U.K) results were used to distinguish the two groups. The LTBI group was TST-positive (TST>10 mm) and IGRA-positive while the healthy donors were TST-negative (TST<5 mm) and IGRA-negative.