Publications by authors named "Xiaorui Lu"

6 Publications

  • Page 1 of 1

Redox-sensitive transcriptional regulator SoxR directly controls antibiotic production, development and thiol-oxidative stress response in Streptomyces avermitilis.

Microb Biotechnol 2021 May 5. Epub 2021 May 5.

State Key Laboratory of Agrobiotechnology and College of Biological Sciences, China Agricultural University, Beijing, China.

The redox-sensitive transcriptional regulator SoxR is conserved in bacteria. Its role in mediating protective response to various oxidative stresses in Escherichia coli and related enteric bacteria has been well established. However, functions and regulatory mechanisms of SoxR in filamentous Streptomyces, which produce half of known antibiotics, are unclear. We report here that SoxR pleiotropically regulates antibiotic production, morphological development, primary metabolism and thiol-oxidative stress response in industrially important species Streptomyces avermitilis. SoxR stimulated avermectin production by directly activating ave structural genes. Four genes (sav_3956, sav_4018, sav_5665 and sav_7218) that are homologous to targets of S. coelicolor SoxR are targeted by S. avermitilis SoxR. A consensus 18-nt SoxR-binding site, 5'-VSYCNVVMHNKVKDGMGB-3', was identified in promoter regions of sav_3956, sav_4018, sav_5665, sav_7218 and target ave genes, leading to prediction of the SoxR regulon and confirmation of 11 new targets involved in development (ftsH), oligomycin A biosynthesis (olmRI), primary metabolism (metB, sav_1623, plcA, nirB, thiG, ndh2), transport (smoE) and regulatory function (sig57, sav_7278). SoxR also directly activated three key developmental genes (amfC, whiB and ftsZ) and promoted resistance of S. avermitilis to thiol-oxidative stress through activation of target trx and msh genes. Overexpression of soxR notably enhanced antibiotic production in S. avermitilis and S. coelicolor. Our findings expand our limited knowledge of SoxR and will facilitate improvement of methods for antibiotic overproduction in Streptomyces species.
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http://dx.doi.org/10.1111/1751-7915.13813DOI Listing
May 2021

Microvesicles from Schwann-Like Cells as a New Biomaterial Promote Axonal Growth.

J Biomed Nanotechnol 2021 Feb;17(2):291-302

Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.

Schwann cells promote axonal regeneration following peripheral nerve injury. However, in terms of clinical treatment, the therapeutic effects of Schwann cells are limited by their source. The transmission of microvesicles from neuroglia cells to axons is a novel communication mechanism in axon regeneration.To evaluate the effect of microvesicles released from Schwann-like cells on axonal regeneration, neural stem cells derived from human embryonic stem cells differentiated into Schwann-like cells, which presented a typical morphology and characteristics similar to those of schwann cells. The glial markers like were upregulated, whereas the neural stem markers like were significantly downregulated in schwann-like cells. Microvesicles enhanced axonal growth in dorsal root ganglia neurons and regulated GAP43 expression in neuron-like cells (N2A and PC12) through the PTEN/PI3 K/Akt signaling pathway. A 5 mm section of sciatic nerve was transected in Sprague-Dawley rats. With microvesicles transplantation, regenerative nerves were evaluated after 6 weeks. Microvesicles increased sciatic function index scores, delayed gastrocnemius muscle atrophy and elevated III-tubulin-labeled axons Schwann-like cells serve as a convenient source and promote axonal growth by secreting microvesicles, which may potentially be used as bioengineering materials for nerve tissue repair.
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http://dx.doi.org/10.1166/jbn.2021.3037DOI Listing
February 2021

Long non-coding RNA SNHG15 regulates cardiomyocyte apoptosis after hypoxia/reperfusion injury via modulating miR-188-5p/PTEN axis.

Arch Physiol Biochem 2020 Sep 24:1-8. Epub 2020 Sep 24.

Department of Internal Medicine-Cardiovascular, Ningxia Yongning County People's Hospital, Ningxia, PR China.

Nowadays the most effective way to cure myocardial infarction (MI) is reperfusion, which inevitably leads to cardiomyocyte apoptosis. In this study, we discussed the functions of SNHG15 in regulating cardiomyocyte apoptosis through the modulation of miR-188-5p/PTEN axis. We examined the links between SNHG15 and miR-188-5p/PTEN in mice with MI. Extensive experiments, measurements and comparisons were performed, including RT-PCR, western blotting, luciferase reporter assay, flow cytometry analysis etc. Through a series of comparisons and analysis, we discovered that SNHG15 could interact with the miR-188-5p/PTEN axis and impact the cellular physiology of cardiomyocyte apoptosis. PTEN was upregulated in hypoxia cells, but this effect was attenuated by miR-188-5p. MiR-188-5p could combine with SNHG15 and PTEN, and form a SNHG15-miR-188-5p-PTEN axis, which regulated the apoptosis of MCs. These results suggest that LncRNA SNHG15 regulates cardiomyocyte apoptosis induced by hypoxia or reperfusion injury through modulating of miR-188-5p/PTEN axis.
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http://dx.doi.org/10.1080/13813455.2020.1819336DOI Listing
September 2020

The ROK-family regulator Rok7B7 directly controls carbon catabolite repression, antibiotic biosynthesis, and morphological development in Streptomyces avermitilis.

Environ Microbiol 2020 12 18;22(12):5090-5108. Epub 2020 Jun 18.

State Key Laboratory of Agrobiotechnology and College of Biological Sciences, China Agricultural University, Beijing, China.

Carbon catabolite repression (CCR) is a common phenomenon in bacteria that modulates expression of genes involved in uptake of alternative carbon sources. In the filamentous streptomycetes, which produce half of all known antibiotics, the precise mechanism of CCR is yet unknown. We report here that the ROK-family regulator Rok7B7 pleiotropically controls xylose and glucose uptake, CCR, development, as well as production of the macrolide antibiotics avermectin and oligomycin A in Streptomyces avermitilis. Rok7B7 directly repressed structural genes for avermectin biosynthesis, whereas it activated olmRI, the cluster-situated activator gene for oligomycin A biosynthesis. Rok7B7 also directly repressed the xylose uptake operon xylFGH, whose expression was induced by xylose and repressed by glucose. Both xylose and glucose served as Rok7B7 ligands. rok7B7 deletion led to enhancement and reduction of avermectin and oligomycin A production, respectively, relieved CCR of xylFGH, and increased co-uptake efficiency of xylose and glucose. A consensus Rok7B7-binding site, 5'-TTKAMKHSTTSAV-3', was identified within aveA1p, olmRIp, and xylFp, which allowed prediction of the Rok7B7 regulon and confirmation of 11 additional targets involved in development, secondary metabolism, glucose uptake, and primary metabolic processes. Our findings will facilitate methods for strain improvement, antibiotic overproduction, and co-uptake of xylose and glucose in Streptomyces species.
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http://dx.doi.org/10.1111/1462-2920.15094DOI Listing
December 2020

BldD, a master developmental repressor, activates antibiotic production in two Streptomyces species.

Mol Microbiol 2020 01 19;113(1):123-142. Epub 2019 Oct 19.

State Key Laboratory of Agrobiotechnology and College of Biological Sciences, China Agricultural University, Beijing, China.

BldD generally functions as a repressor controlling morphological development of Streptomyces. In this work, evidences that BldD also activates antibiotic production are provided. In Streptomyces roseosporus (which produces daptomycin widely used for treatment of human infections), deletion of bldD notably reduced daptomycin production, but enhanced sporulation. BldD stimulated daptomycin production by directly activating transcription of dpt structural genes and dptR3 (which encodes an indirect activator of daptomycin production), and repressed its own gene. BldD-binding sites on promoter regions of dptE, dptR3, and bldD were all found to contain BldD box-like sequences, facilitating prediction of new BldD targets. Two Streptomyces global regulatory genes, adpA and afsR, were confirmed to be directly activated by BldD. The protein AfsR was shown to act as an activator of daptomycin production, but a repressor of development. BldD directly represses nine key developmental genes. In Streptomyces avermitilis (which produces effective anthelmintic agents avermectins), BldD homolog (BldDsav) directly activates avermectin production through ave structural genes and cluster-situated activator gene aveR. This is the first report that BldD activates antibiotic biosynthesis both directly and via a cascade mechanism. BldD homologs are widely distributed among Streptomyces, our findings suggest that BldD may activate antibiotic production in other Streptomyces species.
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http://dx.doi.org/10.1111/mmi.14405DOI Listing
January 2020

SAV4189, a MarR-Family Regulator in , Activates Avermectin Biosynthesis.

Front Microbiol 2018 26;9:1358. Epub 2018 Jun 26.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.

The bacterial species is an important industrial producer of avermectins, which are widely utilized as effective anthelmintic and insecticidal drugs. We used gene deletion, complementation, and overexpression experiments to identify SAV4189, a MarR-family transcriptional regulator (MFR) in this species, as an activator of avermectin biosynthesis. SAV4189 indirectly stimulated avermectin production by altering expression of cluster-situated activator gene , and directly repressed the transcription of its own gene () and adjacent cotranscribed gene (which encodes an unknown transmembrane efflux protein). A consensus 13-bp palindromic sequence, 5'-TTGCCYKHRSCAA-3' (Y = T/C; K = T/G; H = A/C/T; R = A/G; S = C/G), was found within the SAV4189-binding sites of its own promoter region, and shown to be essential for binding. The SAV4189 regulon was thus predicted based on bioinformatic analysis. Night new identified SAV4189 targets are involved in transcriptional regulation, primary metabolism, secondary metabolism, and stress response, reflecting a pleiotropic role of SAV4189. , the important target gene of SAV4189, exerted a negative effect on avermectin production. overexpression and deletion in wild-type and industrial strains significantly increased avermectin production. SAV4189 homologs are widespread in other species. overexpression in the model species also enhanced antibiotic production. The strategy of increasing yield of important antibiotics by engineering of SAV4189 homologs and target gene may potentially be extended to other industrial species. In addition, SAV4189 bound and responded to exogenous antibiotics hygromycin B and thiostrepton to modulate its DNA-binding activity and transcription of target genes. SAV4189 is the first reported exogenous antibiotic receptor among MFRs.
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http://dx.doi.org/10.3389/fmicb.2018.01358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036246PMC
June 2018