Engineered biosynthesis of milbemycins in the avermectin high-producing strain Streptomyces avermitilis

Additional file 3 : Figure S2. HPLC analysis of milbemycins produced from S. avermitilis mutant strains and authentic standard milbemycins

Whole-genome sequencing and analysis of Streptomyces strains producing multiple antinematode drugs

Background : Nematodes are parasitic animals that cause over 100 billion US dollars loss in agricultural business. The whole-genomes of two Streptomyces strains, Streptomyces spectabilis KCTC9218T and Streptomyces sp. AN091965, were sequenced. Both strains produce spectinabilin, an antinematode drug. Its secondary metabolism was examined to aid the development of an efficient nematicidal drug-producing host strain. Results : The whole-genome sequences of S. spectabilis KCTC9218T and Streptomyces sp. AN091965 were analyzed using PacBio and Illumina sequencing platforms, and assembled using hybrid methodology. The total contig lengths for KCTC9218T and AN091965 were 9.97 Mb and 9.84 Mb, respectively. A total of 8,374 and 8,054 protein-coding genes, as well as 39 and 45 secondary metabolite biosynthetic gene clusters were identified in KCTC9218T and AN091965, respectively. 18.4 ± 6.45 mg/L and 213.89 ± 21.30 mg/L of spectinabilin were produced by S. spectabilis KCTC9218T and Streptomyces sp. AN091965, respectively. Pine wilt disease caused by nematode was successfully prevented by lower concentration of spectinabilin injection than that of abamectin recommended by its manufacturer. Production of multiple antinematode drugs, including spectinabilin, streptorubin B, and undecylprodigiosin was observed in both strains using high-resolution liquid chromatography mass spectrometry (LC–MS) analysis. Conclusions : Whole-genome sequencing of spectinabilin-producing strains, coupled with bioinformatics and mass spectrometry analyses, revealed the production of multiple nematicidal drugs in the KCTC9218T and AN091965 strains. Especially, Streptomyces sp. AN091965 showed high production level of spectinabilin, and this study provides crucial information for the development of potential nematicidal drug producers.This work was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) through“Crop Viruses and Pests Response Industry Technology Development” Program (No.321110–4) funded by Ministry of Agriculture, Food and Rural Afairs (MAFRA), National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No.2022R1A2C3004621) and the Ministry of Education (2022R1I1A1A01068507), and the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2020M3H1A1073304)

Clinical Features, Risk Factors and Outcomes of Bacteremia due to Enterococci with High-Level Gentamicin Resistance: Comparison with Bacteremia due to Enterococci without High-Level Gentamicin Resistance

High-level gentamicin resistance (HLGR) in enterococci has increased since the 1980s, but the clinical significance of the resistance and its impact on outcome have not been established. One hundred and thirty-six patients with bacteremia caused by enterococci with HLGR (HLGR group) were compared with 79 patients with bacteremia caused by enterococci without HLGR (non-HLGR group). Hematologic malignancy, neutropenia, Enterococcus faecium infection, nosocomial infection and monomicrobial bacteremia were more common in the HLGR group than the non-HLGR group, and APACHE II scores were also higher (P<0.05, in each case). Neutropenia, monomicrobial infection, stay in intensive care at culture, and use of 3rd generation cephalosporin, were independent risk factors for acquisition of HLGR enterococcal bacteremia. Fourteen-day and 30-day mortalities were higher in the HLGR group than the non-HLGR group in univariate analysis (37% vs. 15%, P=0.001; 50% vs. 22%, P<0.001). However, HLGR was not an independent risk factor for mortality due to enterococcal bacteremia in multivariate analysis. Therefore, HLGR enterococcal bacteremia is associated with more severe comorbid conditions and higher mortality than non-HLGR enterococcal bacteremia but the HLGR itself does not contribute significantly to mortality

Salvage Treatment for Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia: Efficacy of Linezolid With or Without Carbapenem

Background. Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high mortality rates, but no treatment strategy has yet been established. We performed this study to evaluate the efficacy of linezolid with or without carbapenem in salvage treatment for persistent MRSA bacteremia. Methods. All adult patients with persistent MRSA bacteremia for >= 7 days from January 2006 through March 2008 who were treated at Seoul National University Hospital were studied. The results of linezolid salvage therapy with or without carbapenem were compared with those of salvage therapy with vancomycin plus aminoglycosides or rifampicin. Results. Thirty-five patients with persistent MRSA bacteremia were studied. The early microbiological response (ie, negative results for follow-up blood culture within 72 hours) was significantly higher in the linezolid-based salvage therapy group than the comparison group (75% vs 17%; P = .006). Adding aminoglycosides or rifampicin to vancomycin was not successful in treating any of the patients, whereas linezolid-based therapy gave an 88% salvage success rate (P < .001). The S. aureus-related mortality rate was lower for patients treated with a linezolid salvage regimen than for patients continually treated with a vancomycin-based regimen (13% vs 53%; P = .030). Conclusions. Linezolid-based salvage therapy effectively eradicated S. aureus from the blood for patients with persistent MRSA bacteremia. The salvage success rate was higher for linezolid therapy than for vancomycin-based combination therapy.Jenkins TC, 2008, CLIN INFECT DIS, V46, P1000, DOI 10.1086/529190Falagas ME, 2008, LANCET INFECT DIS, V8, P53, DOI 10.1016/S1473-3099(07)70312-2Hawkins C, 2007, ARCH INTERN MED, V167, P1861Kollef MH, 2007, CLIN INFECT DIS, V45, pS191, DOI 10.1086/519470Micek ST, 2007, CLIN INFECT DIS, V45, pS184, DOI 10.1086/519471*CLIN LAB STAND I, 2007, M100S17 CLIN LAB STAHidayat LK, 2006, ARCH INTERN MED, V166, P2138Howden BP, 2006, ANTIMICROB AGENTS CH, V50, P3039, DOI 10.1128/AAC.00422-06Hageman JC, 2006, CLIN INFECT DIS, V43, pE42Jacqueline C, 2006, ANTIMICROB AGENTS CH, V50, P2547, DOI 10.1128/AAC.01501-05Sakoulas G, 2006, CLIN INFECT DIS, V42, pS40Jones RN, 2006, CLIN INFECT DIS, V42, pS13Khatib R, 2006, SCAND J INFECT DIS, V38, P7, DOI 10.1080/00365540500372846Wu VC, 2006, CLIN INFECT DIS, V42, P66Jacqueline C, 2005, ANTIMICROB AGENTS CH, V49, P45, DOI 10.1128/AAC.49.1.45-51.2005*CDCP, 2005, CA MRSA CLIN FAQS CDFowler VG, 2004, J INFECT DIS, V190, P1140Wisplinghoff H, 2004, CLIN INFECT DIS, V39, P309, DOI 10.1086/421946Khosrovaneh A, 2004, CLIN INFECT DIS, V38, P1328Howden BP, 2004, CLIN INFECT DIS, V38, P521KIM SH, 2004, 42 ANN M INF DIS SOC, P142Fowler VG, 2003, ARCH INTERN MED, V163, P2066Kim SH, 2003, CLIN INFECT DIS, V37, P794Moise PA, 2002, J ANTIMICROB CHEMOTH, V50, P1017, DOI 10.1093/jac/dkf215Li JS, 2000, CLIN INFECT DIS, V30, P633You I, 2000, DIAGN MICR INFEC DIS, V36, P37Lowy FD, 1998, NEW ENGL J MED, V339, P520Hiramatsu K, 1997, LANCET, V350, P1670LIBMAN H, 1984, ARCH INTERN MED, V144, P5411

Can a routine follow-up blood culture be justified in Klebsiella pneumoniae bacteremia? a retrospective case–control study

Background : The need for mandatory confirmation of negative conversion in Klebsiella pneumoniae bacteremia (KpB) has not been adequately addressed. We conducted a retrospective case–control study of adult patients with KpB over a 5-year period in two tertiary-care hospitals to determine the risk factors for persistent bacteremia and to reevaluate the necessity of follow-up blood culture in KpB. Methods : Persistent KpB is defined as the finding of K. pneumoniae in more than two separate blood-culture samples for longer than a two-day period in a single episode. The case- and control-groups were patients with persistent and non-persistent KpB, respectively, and they were matched 1-to-3 according to age and gender. Results : Among 1068 KpB episodes analyzed after excluding polymicrobial infection and repeated KpB, follow-up blood cultures were performed in 862 cases (80.7%), 62 of which (7.2%) were persistent. Independent risk factors for persistence were intra-abdominal infection, higher Charlsons comorbidity weighted index score, prior solid organ transplantation, and unfavorable treatment response, which was defined as positivity for at least two parameters among fever, leukocytosis, and no decrease of C-reactive protein on the second day after initial culture. A proposed scoring system using four variables, namely, intra-abdominal infection, nosocomial KpB, fever and lack of C-reactive protein decrease, the last two being assessed on the second day after the initial blood culture, showed that only 4.9% of the patients with no risk factors or with only intra-abdominal infection had persistent KpB. Conclusions : Though persistent KpB is uncommon, follow-up blood culture was performed in as many as 80% of the cases in this study. A more careful clinical assessment is warranted to reduce the cost and patient inconvenience involved in follow-up blood culture.Peer Reviewe

New Era of Air Quality Monitoring from Space: Geostationary Environment Monitoring Spectrometer (GEMS)

GEMS will monitor air quality over Asia at unprecedented spatial and temporal resolution from GEO for the first time, providing column measurements of aerosol, ozone and their precursors (nitrogen dioxide, sulfur dioxide and formaldehyde). Geostationary Environment Monitoring Spectrometer (GEMS) is scheduled for launch in late 2019 - early 2020 to monitor Air Quality (AQ) at an unprecedented spatial and temporal resolution from a Geostationary Earth Orbit (GEO) for the first time. With the development of UV-visible spectrometers at sub-nm spectral resolution and sophisticated retrieval algorithms, estimates of the column amounts of atmospheric pollutants (O3, NO2, SO2, HCHO, CHOCHO and aerosols) can be obtained. To date, all the UV-visible satellite missions monitoring air quality have been in Low Earth orbit (LEO), allowing one to two observations per day. With UV-visible instruments on GEO platforms, the diurnal variations of these pollutants can now be determined. Details of the GEMS mission are presented, including instrumentation, scientific algorithms, predicted performance, and applications for air quality forecasts through data assimilation. GEMS will be onboard the GEO-KOMPSAT-2 satellite series, which also hosts the Advanced Meteorological Imager (AMI) and Geostationary Ocean Color Imager (GOCI)-2. These three instruments will provide synergistic science products to better understand air quality, meteorology, the long-range transport of air pollutants, emission source distributions, and chemical processes. Faster sampling rates at higher spatial resolution will increase the probability of finding cloud-free pixels, leading to more observations of aerosols and trace gases than is possible from LEO. GEMS will be joined by NASA&apos;s TEMPO and ESA&apos;s Sentinel-4 to form a GEO AQ satellite constellation in early 2020s, coordinated by the Committee on Earth Observation Satellites (CEOS)

Newly identified maltol derivatives in Korean Red Ginseng and their biological influence as antioxidant and anti-inflammatory agents

Background: Korean Red Ginseng is a major source of bioactive substances such as ginsenosides. Efficacy of red ginseng extract (RGE), which contains not only saponins but also various non-saponins, has long been studied. In the water-soluble component-rich fraction of RGE (WS), a byproduct generated in the process of extracting saponins from the RGE, we identified previously unidentified molecules and confirmed their efficacy. Methods: The RGE was prepared and used to produce WS, whose components were isolated sequentially according to their water affinity. The new compounds from WS were fractionized and structurally analyzed using nuclear magnetic resonance spectroscopy. Physiological applicability was evaluated by verifying the antioxidant and anti-inflammatory efficacies of these compounds in vitro. Results: High-performance liquid chromatography confirmed that the obtained WS comprised 11 phenolic acid and flavonoid substances. Among four major compounds from fractions 1−4 (F1–4) of WS, two compounds from F3 and F4 were newly identified in red ginseng. The analysis results show that these compound molecules are member of the maltol-structure-based glucopyranose series, and F1 and F4 are particularly effective for decreasing oxidative stress levels and inhibiting nitric oxide secretion, interleukin (IL)-1β and IL-6, and tumor necrosis factor-α. Conclusion: Our findings suggest that a few newly identified maltol derivatives, such as red ginseng-derived non-saponin in the WS, exhibit antioxidant and anti-inflammatory effects, making them viable candidates for application to pharmaceutical, cosmetic, and functional food materials

New Flavonolignan Glycosides from the Aerial Parts of Zizania latifolia

Two new flavonolignan glycosides, tricin-4\u27-O-(threo-β-guaiacylglyceryl) ether 7\u27\u27-O-β-D-glucopyranose (4) and tricin-4\u27-O-(erythro-β-guaiacylglyceryl) ether 7\u27\u27-O-β-D-glucopyranose (5) were isolated from the roots of Zizania latifolia, together with tricin-7-O-β-D-glucopyranose (1), tricin-4\u27-O-(threo-β-guaiacylglyceryl) ether 7-O-β-D-glucopyranose (2), and tricin-4\u27-O-(erythro-β-guaiacylglyceryl) ether 7-O-β-D-glucopyranose (3). Their structures were identified on the basis of spectroscopic techniques, including HR-ESI/MS, 1D-NMR (1H, 13C, DEPT), 2D-NMR (gCOSY, gHSQC, gHMBC), and IR spectroscopy

High-yield production of multiple O-methylated phenylpropanoids by the engineered Escherichia coli–Streptomyces cocultivation system

Abstract Background O-Methylated phenylpropanoids, which are generally present in small amounts in plants, have improved or distinct biological activities and pharmacological properties as opposed to their unmethylated counterparts. Although microbial production could be a useful tool for the efficient and environment-friendly production of methylated phenylpropanoids, a high-yield microbial production of neither tri-methylated stilbenes nor di-/tri-methylated flavonoids has been achieved to date. Results A methyltransferase from Streptomyces avermitilis (SaOMT2), which has been known to possess 7-O-methylation activity toward several flavonoids, exhibited more diverse regiospecificity and catalyzed mono-, di-, and tri-methylation of stilbene, flavanone, and flavone when it was expressed in Streptomyces venezuelae. For the efficient production of multi-methylated phenylpropanoids, a cocultivation system was developed by employing engineered Escherichia coli strains producing pterostilbene, naringenin, and apigenin, respectively, along with SaOMT2-expressing S. venezuelae mutant. Consequently, high-yield microbial production of tri-methylated stilbenes and di-/tri-methylated flavonoids (including 3,5,4′-trimethoxystilbene, 5-hydroxy-7,4′-dimethoxyflavanone, 4′-hydroxy-5,7-dimethoxyflavanone, 5,7,4′-trimethoxyflavanone, 5-hydroxy-7,4′-dimethoxyflavone, and 5,7,4′-trimethoxyflavone) has been demonstrated for the first time. Conclusions This cocultivation system based on the phenylpropanoid-producing E. coli and SaOMT2-expressing S. venezuelae provides an efficient tool for producing scarce and potentially valuable multi-methylated phenylpropanoids and will enable further development of these compounds as pharmaceuticals and nutraceuticals