Deinococcus radiodurans is an extreme bacterium known for its high resistance to stresses including radiation and oxidants. The ability of D. radiodurans to reduce Au(III) and biosynthesize gold nanoparticles (AuNPs) was investigated in aqueous solution by ultraviolet and visible (UV/Vis) absorption spectroscopy, electron microscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). D. radiodurans efficiently synthesized AuNPs from 1 mM Au(III) solution in 8 h. The AuNPs were of spherical, triangular and irregular shapes with an average size of 43.75 nm and a polydispersity index of 0.23 as measured by DLS. AuNPs were distributed in the cell envelope, across the cytosol and in the extracellular space. XRD analysis confirmed the crystallite nature of the AuNPs from the cell supernatant. Data from the FTIR and XPS showed that upon binding to proteins or compounds through interactions with carboxyl, amine, phospho and hydroxyl groups, Au(III) may be reduced to Au(I), and further reduced to Au(0) with the capping groups to stabilize the AuNPs. Biosynthesis of AuNPs was optimized with respect to the initial concentration of gold salt, bacterial growth period, solution pH and temperature. The purified AuNPs exhibited significant antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria by damaging their cytoplasmic membrane. Therefore, the extreme bacterium D. radiodurans can be used as a novel bacterial candidate for efficient biosynthesis of AuNPs, which exhibited potential in biomedical application as an antibacterial agent.

Background: Nanoplastics have been recently found widely distributed in our natural environment where ubiquitously bacteria are major participants in various material cycles. Understanding how nanoplastics interact with bacterial cell membrane is critical to grasp their uptake processes as well as to analyze their associated risks in ecosystems and human microflora. However, little is known about the detailed interaction of differentially charged nanoplastics with bacteria. The present work experimentally and theoretically demonstrated that nanoplastics enter into bacteria depending on the surface charges and cell envelope structural features, and proved the shielding role of membrane lipids against nanoplastics. Results: Positively charged polystyrene nanoplastics (PS-NH₂, 80 nm) can efficiently translocate across cell membranes, while negatively charged PS (PS-COOH) and neutral PS show almost no or much less efficacy in translocation. Molecular dynamics simulations revealed that the PS-NH₂ displayed more favourable electrostatic interactions with bacterial membranes and was subjected to internalisation through membrane penetration. The positively charged nanoplastics destroy cell envelope of Gram-positive B. subtilis by forming membrane pore, while enter into the Gram-negative E. coli with a relatively intact envelope. The accumulated positively charged nanoplastics conveyed more cell stress by inducing a higher level of reactive oxygen species (ROS). However, the subsequently released membrane lipid-coated nanoplastics were nearly nontoxic to cells, and like wise, stealthy bacteria wrapped up with artifical lipid layers became less sensitive to the positively charged nanoplastics, thereby illustrating that the membrane lipid can shield the strong interaction between the positively charged nanoplastics and cells. Conclusions: Our findings elucidated the molecular mechanism of nanoplastics’ interaction and accumulation within bacteria, and implied the shielding and internalization effect of membrane lipid on toxic nanoplastics could promote bacteria for potential plastic bioremediation. Graphical

Primary and acquired drug resistance is one of the main obstacles encountered in high-grade serous ovarian cancer (HGSC) chemotherapy. Cisplatin induces DNA damage through cross-linking and long integrated non-coding RNAs (lincRNAs) play an important role in chemical induced DNA-damage response, which suggests that lincRNAs may be also associated with cisplatin resistance. However, the mechanism of long integrated non-coding RNAs (lincRNAs) acting on cisplatin resistance is not well understood. Here, we showed that expression of lin-RECK-3, H19, LUCAT1, LINC00961 and linc-CARS2-2 was enhanced in cisplatin-resistant A2780-DR cells, while transcriptome sequencing showed decreased Linc-TNFRSF19-1 and LINC00515 expression. Additionally, we verified that different H19 expression levels in HGSC tissues showed strong correlation with cancer recurrence. H19 knockdown in A2780-DR cells resulted in recovery of cisplatin sensitivity in vitro and in vivo. Quantitative proteomics analysis indicated that six NRF2-targeted proteins, including NQO1, GSR, G6PD, GCLC, GCLM and GSTP1 involved in the glutathione metabolism pathway, were reduced in H19-knockdown cells. Furthermore, H19-knockdown cells were markedly more sensitive to hydrogen-peroxide treatment and exhibited lower glutathione levels. Our results reveal a previously unknown link between H19 and glutathione metabolism in the regulation of cancer-drug resistance.

Summary: Two‐component systems are predominant signal transduction pathways in prokaryotes, and also exist in many archaea as well as some eukaryotes. A typical TCS consists of a histidine kinase and a cognate response regulator. In this study, a novel gene encoding a response regulator (we designate it drRRA) is identified to be essential for the extreme radioresistance of Deinococcus radiodurans. DrRRA null mutant (we designate it MR) is sensitive to gamma‐radiation compared with the wild‐type strain. Transcriptional assays show that numerous genes are changed in their transcriptional levels in MR at exponential growth phase under normal or gamma‐radiation condition. Most of them are related to stress response and DNA repair. Antioxidant activity assays exhibit that both superoxide dismutases and catalases are decreased in the mutant, whereas Western blotting assays show that RecA and PprA are also reduced in MR, verifying the microarray and quantitative real‐time PCR data. Furthermore, pulsed‐field gel electrophoresis assay demonstrates that deletion of drRRA results in the delay of genome restitution. These data support the hypothesis that DrRRA contributes to the extreme radioresistance of D. radiodurans through its regulatory role in multiple pathways such as antioxidation and DNA repair pathways.

In bacteria, OxyR is a peroxide sensor and transcription regulator, which can sense the presence of reactive oxygen species and induce antioxidant system. When the cells are exposed to H₂O₂, OxyR protein is activated via the formation of a disulfide bond between the two conserved cysteine residues (C199 and C208). In Deinococcus radiodurans, a previously unreported special characteristic of DrOxyR (DR0615) is found with only one conserved cysteine. dr0615 gene mutant is hypersensitive to H₂O₂, but only a little to ionizing radiation. Site-directed mutagenesis and subsequent in vivo functional analyses revealed that the conserved cysteine (C210) is necessary for sensing H₂O₂, but its mutation did not alter the binding characteristics of OxyR on DNA. Under oxidant stress, DrOxyR is oxidized to sulfenic acid form, which can be reduced by reducing reagents. In addition, quantitative real-time PCR and global transcription profile results showed that OxyR is not only a transcriptional activator (e.g., katE, drb0125), but also a transcriptional repressor (e.g., dps, mntH). Because OxyR regulates Mn and Fe ion transporter genes, Mn/Fe ion ratio is changed in dr0615 mutant, suggesting that the genes involved in Mn/Fe ion homeostasis, and the genes involved in antioxidant mechanism are highly cooperative under extremely oxidant stress. In conclusion, these findings expand the OxyR family, which could be divided into two classes: typical 2-Cys OxyR and 1-Cys OxyR.