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| 2. |
- Bjerketorp, Joakim, et al.
(författare)
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Antibacterial 3,6-Disubstituted 4-Hydroxy-5,6-dihydro-2H-pyran-2-ones from Serratia plymuthica MF371-2
- 2017
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Ingår i: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 80:11, s. 2997-3002
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Tidskriftsartikel (refereegranskat)abstract
- Bioassay-guided fractionation of culture extracts of Serratia plymuthica strain MF371-2 resulted in the isolation of two new antibacterial compounds with potent activity against Gram-positive bacteria, including Staphylococcus aureus LMG 15975 (MRSA). A spectroscopic investigation, in combination with synthesis, enabled the characterization of the compounds as 3-butyryl-4-hydroxy-6-heptyl-5,6-dihydro2H-pyran-2-one (plymuthipyranone A, 1) and 3-butyry1-4-hydroxy-6-nony1-5,6-dihydro-2H-pyran-2-one (plymuthipyranone B, 2). The MIC values for 1 and 2 against S. aureus LMG 15975 were determined to be 1-2 mu g mL(-1) and 0.8 mu g mL(-1), respectively. Compound 2 was found to have potent activity against many strains of S. aureus, including several mupirocin-resistant strains, other species of Staphylococcus, and vancomycin-resistant enterococci. Compound 2 was slightly cytotoxic for human cells, with CC50 values between 4.7 and 40 mu g mL(-1), but the CC50/MIC ratio was >= 10 for many tested combinations of human cells and bacteria, suggesting its possible use as an antibacterial agent. Several analogues were synthesized with different alkyl groups in the 3- and 6-positions (6-13), and their biological properties were evaluated. It was concluded that the activity of the compounds increased with the lengths of the alkyl and acyl substituents.
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| 3. |
- Bjerketorp, Joakim, et al.
(författare)
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Selective Isolation of Multidrug-Resistant Pedobacter spp., Producers of Novel Antibacterial Peptides
- 2021
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Twenty-eight multidrug-resistant bacterial strains closely related or identical to Pedobacter cryoconitis, Pedobacter lusitanus and Pedobacter steynii were isolated from soil samples by selection for multidrug-resistance. Approximately 3-30% of the selected isolates were identified as Pedobacter, whereas isolation without antibiotics did not yield any isolates of this genus. Next generation sequencing data showed Pedobacter to be on 69th place among the bacterial genera (0.32% of bacterial sequences). The Pedobacter isolates produced a wide array of novel compounds when screened by UHPLC-MS/MSMS, and hierarchical cluster analysis resulted in several distinct clusters of compounds produced by specific isolates of Pedobacter, and most of these compounds were found to be peptides. The Pedobacter strain UP508 produced isopedopeptins, whereas another set of strains produced pedopeptins, which both are known cyclic lipodepsipeptides produced by Pedobacter sp. Other Pedobacter strains produced analogous peptides with a sequence variation. Further strains of Pedobacter produced additional novel antibacterial cyclic lipopeptides (ca 800 or 1400 Da in size) and/or linear lipopeptides (ca 700-960 Da in size). A 16S rRNA phylogenetic tree for the Pedobacter isolates revealed several distinct clades and subclades of isolates. One of the subclades comprised isolates producing isopedopeptin analogs, but the isopedopeptin producing isolate UP508 was clearly placed on a separate branch. We suggest that the non-ribosomal peptide synthases producing pedopeptins, isopedopeptins, and the analogous peptides, may derive from a common ancestral non-ribosomal peptide synthase gene cluster, which may have been subjected to a mutation leading to changed specificity in one of the modules and then to a modular rearrangement leading to the changed sequence found in the isopedopeptins produced by isolate UP508.
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| 4. |
- Broberg, Anders, et al.
(författare)
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In-peptide amino acid racemization via inter-residue oxazoline intermediates during acidic hydrolysis
- 2021
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Ingår i: Amino Acids. - : Springer Nature. - 0939-4451 .- 1438-2199. ; 53:3, s. 323-331
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Tidskriftsartikel (refereegranskat)abstract
- Isopedopeptins are antibiotic cyclic lipodepsipeptides containing the subsequence L-Thr-L-2,3-diaminopropanoic acid-D-Phe-L-Val/L-3-hydroxyvaline. Acidic hydrolysis of isopedopeptins in D2O showed the D-Phe residues to racemize extensively in peptides with L-3-hydroxyvaline but not in peptides with L-Val. Similarly, one Leu residue in pedopeptins, which are related peptides containing the subsequence Leu-2,3-diaminopropanoic acid-Leu-L-Val/L-3-hydroxyvaline, was found to racemize in peptides with L-3-hydroxyvaline. Model tetrapeptides, L-Ala-L-Phe-L-Val/3-hydroxyvaline-L-Ala, gave the corresponding results, i.e. racemization of L-Phe only when linked to a L-3-hydroxyvaline. We propose the racemization to proceed via an oxazoline intermediate involving Phe/Leu and the L-3-hydroxyvaline residues. The 3-hydroxyvaline residue may form a stable tertiary carbocation by loss of the sidechain hydroxyl group as water after protonation. Elimination of the Phe/Leu H-2 and ring-closure from the carbonyl oxygen onto the carbocation results in the suggested oxazoline intermediate. The reversed reaction leads to either retained or inversed configuration of Phe/Leu. Such racemization during acidic hydrolysis may occur whenever a 3-hydroxyvaline residue or any amino acid that can form a stable carbocation on the C-3, is present in a peptide. The proposed mechanism for racemization was supported by incorporation of O-18 in the 3-hydroxyvaline sidechain when the acidic hydrolysis was performed in H2O/(H2O)-O-18 (1:1). The 2,3-diaminopropanoic residues of isopedopeptins and pedopeptins were also found to racemize during acidic hydrolysis, as previously described. Based on the results, the configuration of the Leu and 2,3-diaminopropanoic acid residues of the pedopeptins were reassigned to be L-Leu and D-Leu, and 2 x L-2,3-diaminopropanoic acid.
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| 5. |
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| 6. |
- Grandien, Christina, et al.
(författare)
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Efter flodvågskatastrofen. : Svenska folkets åsikter om och förtroende för myndigheter, medier och politiker
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Flodvågskatastrofen i Sydostasien på annandagen den 26 december 2004 var en av de värsta naturkatastroferna i modern tid. Den drabbade också Sverige hårt, eftersom många svenskar semestrade i Thailand vid tiden för katastrofen. Den svenska krisberedskapen sattes på prov – ett prov som många anser att den inte klarade av. Det framgår av denna rapport, som undersöker allmänhetens åsikter om och förtroende för myndigheter, politiska organ och ledare samt medier, och hur allmänheten själv uppfattar att dess åsikter och förtroendebedömningar har påverkats av flodvågskatastrofen. Rapporten bygger på en riksrepresentativ telefonintervjuundersökning och en fokusgruppsundersökning. Resultaten visar att den svenska allmänheten är kritisk – inte minst mot regeringen med Göran Persson i spetsen och mot utrikesdepartementet under ledning av Laila Freivalds. Medierna anses dock i huvudsak ha skött sin bevakning väl, och allmänheten uppger också ett högre förtroende för journalister än för politiker.
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| 7. |
- Levenfors, Jolanta, et al.
(författare)
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Antibacterial pyrrolidinyl and piperidinyl substituted 2,4-diacetylphloroglucinols from Pseudomonas protegens UP46
- 2020
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Ingår i: Journal of antibiotics (Tokyo. 1968). - : SPRINGERNATURE. - 0021-8820 .- 1881-1469. ; 73:11, s. 739-747
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Tidskriftsartikel (refereegranskat)abstract
- In the search for new antibiotic compounds, fractionation of Pseudomonas protegens UP46 culture extracts afforded several known Pseudomonas compounds, including 2,4-diacetylphloroglucinol (DAPG), as well as two new antibacterial alkaloids, 6-(pyrrolidin-2-yl)DAPG (1) and 6-(piperidin-2-yl)DAPG (2). The structures of 1 and 2 were determined by nuclear magnetic resonance spectroscopy and mass spectrometry. Compounds 1 and 2 were found to have antibacterial activity against the Gram-positive bacteria Staphylococcus aureus and Bacillus cereus, with minimal inhibitory concentration (MIC) 2 and 4 mu g ml(-1), respectively, for 1, and 2 mu g ml(-1) for both pathogens for 2. The MICs for 1 and 2, against all tested Gram-negative bacteria, were >32 mu g ml(-1). The half maximal inhibitory concentrations against HepG2 cells for compounds 1 and 2 were 11 and 18 mu g ml(-1), respectively, which suggested 1 and 2 be too toxic for further evaluation as possible new antibacterial drugs. Stable isotope labelling experiments showed the pyrrolidinyl group of 1 to originate from ornithine and the piperidinyl group of 2 to originate from lysine. The P. protegens acetyl transferase (PpATase) is involved in the biosynthesis of monoacetylphloroglucinol and DAPG. No optical rotation was detected for 1 or 2, and a possible reason for this was investigated by studying if the PpATase may catalyse a stereo-non-specific introduction of the pyrrolidinyl/piperidinyl group in 1 and 2, but unless the PpATase can be subjected to major conformational changes, the enzyme cannot be involved in this reaction. The PpATase is, however, likely to catalyse the formation of 2,4,6-triacetylphloroglucinol from DAPG.
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| 8. |
- Lindqvist, Gunilla, et al.
(författare)
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Intervju med Erik Witting från Mariestad
- 1985
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Annan publikation (populärvet., debatt m.m.)abstract
- Interview with Erik Witting. The interview was conducted by Gunilla Lindqvist and Christina Nord, students of the Swedish School of Library and Information Science in Borås, on February 12, 1985.
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| 9. |
- Lindqvist, Gunilla, et al.
(författare)
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Intervju med Gösta Andersson från Mariestad
- 1985
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Annan publikation (populärvet., debatt m.m.)abstract
- Interview with Gösta Andersson. The interview was conducted by some student(s) of the Swedish School of Library and Information Science in Borås, on February 14, 1985.
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| 10. |
- Nord, Christina, et al.
(författare)
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Antibacterial Isoquinoline Alkaloids from the Fungus Penicillium Spathulatum Em19
- 2019
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:24
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Tidskriftsartikel (refereegranskat)abstract
- In the search for new microbial antibacterial secondary metabolites, two new compounds (1 and 2) were isolated from culture broths of Penicillium spathulatum Em19. Structure determination by nuclear magnetic resonance and mass spectrometry identified the compounds as 6,7-dihydroxy-5,10-dihydropyrrolo[1,2-b]isoquinoline-3-carboxylic acid (1, spathullin A) and 5,10-dihydropyrrolo[1,2-b]isoquinoline-6,7-diol (2, spathullin B). The two compounds displayed activity against both Gram-negative and -positive bacteria, including Escherichia coli, Acinetobacterbaumannii, Enterobactercloacae, Klebsiellapneumonia, Pseudomonasaeruginosa, and Staphylococcusaureus. Compound 2 was more potent than 1 against all tested pathogens, with minimal inhibitory concentrations down to 1 mu g/mL (5 mu M) against S. aureus, but 2 was also more cytotoxic than 1 (50% inhibitory concentrations 112 and 11 mu M for compounds 1 and 2, respectively, towards Huh7 cells). Based on stable isotope labelling experiments and a literature comparison, the biosynthesis of 1 was suggested to proceed from cysteine, tyrosine and methionine via a non-ribosomal peptides synthase like enzyme complex, whereas compound 2 was formed spontaneously from 1 by decarboxylation. Compound 1 was also easily oxidized to the 1,2-benzoquinone 3. Due to the instability of compound 1 and the toxicity of 2, the compounds are of low interest as possible future antibacterial drugs.
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