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- Baranska-Rybak, W, et al.
(författare)
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Glycosaminoglycans inhibit the antibacterial activity of LL-37 in biological fluids
- 2006
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 1460-2091 .- 0305-7453. ; 57:2, s. 260-265
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The antibacterial activity of antimicrobial peptides is influenced by various factors such as salt content, pH and the presence of proteins. In this study, we explored the antibacterial action of the human cathelicidin LL-37 in physiologically relevant conditions, i.e. various human wound fluids, human plasma fractions and serum. Methods: Radial diffusion assays using Staphylococcus aureus and Escherichia coli were employed for the study of antibacterial effects of LL-37 in the presence of 12 different wound fluids, citrate-, heparin- or EDTA-plasma, or human serum. Glycosaminoglycan content of wound fluids was determined by an Alcian Blue-binding assay. Protein content of wound fluids was measured by the Bradford method. A slot-binding assay was used to study the effects of inhibitors on the interaction between LL-37 and glycosaminoglycans. Results: Five of twelve wound fluids derived from acute wounds showed marked inhibitory effects on the antibacterial action of LL-37. The inhibition was significantly correlated with high glycosaminoglycan content in wound fluid. Analogous to these findings, heparin-plasma strongly inhibited the antibacterial effect of LL-37. The interaction between LL-37 and glycosaminoglycans was abrogated by the cationic polymers DEAE-dextran and chitosan, yielding increased activity of LL-37. Conclusions: Glycosaminoglycan-rich biological fluids inhibit the antibacterial effects of LL-37. Furthermore, polycations that bind to glycosaminoglycans increase the antibacterial activities of endogenous antimicrobial peptides in glycosaminoglycan-containing biological fluids.
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| 2. |
- Berglund, Carolina, et al.
(författare)
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Genetic diversity of methicillin-resistant Staphylococcus aureus carrying type IV SCCmec in Orebro County and the western region of Sweden
- 2009
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Ingår i: Journal of Antimicrobial Chemotherapy. - Oxford : Oxford University Press. - 0305-7453 .- 1460-2091. ; 63:1, s. 32-41
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent studies have shown a predominance of type IV SCCmec among the methicillin-resistant Staphylococcus aureus (MRSA) isolated in the low endemic areas of Orebro County and the western region of Sweden. However, many of these isolates were not possible to classify as existing subtypes IVa, IVb, IVc or IVd. METHODS: We analysed 16 such MRSA isolates by multilocus sequence typing, spa typing, staphylocoagulase (SC) typing and detection of type IVg and IVh SCCmec. MRSA that remained as unknown type IV SCCmec were investigated by long-range PCR covering the J1 region; however, only two isolates were possible to amplify by PCR. The nucleotide sequences of the entire SCCmec of these two MRSA were determined. In addition, isolates that had unknown SC types were investigated by nucleotide sequencing of the coa genes. RESULTS: Five of 16 isolates were classified as type IVg SCCmec, and four isolates had type IVh SCCmec. Two subtypes of type IV SCCmec shared J1 regions previously identified in other types of SCCmec, types I.2 and II.2. The novel elements were designated as type IVi and IVj SCCmec. In addition, the genetic backgrounds of these Swedish MRSA were diverse and constituted at least nine sequence types and eight SC types, including four new types of SC. CONCLUSIONS: Type IV SCCmec is occurring in heterogeneous clones of MRSA in Sweden, and the majority of the type IV SCCmec were identified in community-acquired MRSA. We describe two novel subtypes of type IV SCCmec with common J1 regions shared by other types of SCCmec, which indicate that J1 regions occurred as primordial SCC.
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| 3. |
- Chryssanthou, Erja, et al.
(författare)
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Post-antifungal effect of amphotericin B and voriconazole against germinated Aspergillus fumigatus conidia
- 2008
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 61:6, s. 1309-11
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The post-antifungal effect (PAFE) of amphotericin B and voriconazole on germinated Aspergillus fumigatus conidia was studied using the BacT/Alert detection system based on fungal CO(2) production. METHODS: Germinated conidia of A. fumigatus were exposed to 1-10x MIC of amphotericin B for 1 and 4 h and to 2.5-40x MIC of voriconazole for 4 and 24 h. After removal of the drug by washing, similar numbers of exposed and control germlings were inoculated into Pedi-BacT culture bottles. CO(2) production was automatically monitored until the bottles signalled positive. The difference in time for positive signals in drug-exposed and control bottles was used to calculate the PAFE. RESULTS: The killing rate of amphotericin B against germlings was both concentration- and time-dependent, as has been previously found for actively growing hyphae. Similarly, voriconazole showed fungicidal effect after 24 h of exposure, but not after 4 h. Amphotericin B induced a long concentration- and time-dependent PAFE, whereas voriconazole resulted in a short and dose-independent PAFE that was significantly longer after 24 h than after 4 h of exposure. CONCLUSIONS: An automated method is presented for the determination of PAFE on filamentous fungi using quantifiable numbers of germinated conidia. In contrast to previous results obtained from conidia, this method could demonstrate a PAFE of amphotericin B on Aspergillus that shared characteristics similar to that on Candida spp.
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| 9. |
- Goscinski, Gunilla, et al.
(författare)
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Propensity to release endotoxin after two repeated doses of cefuroxime in an in vitro kinetic model : Higher release after the second dose
- 2007
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 60:2, s. 328-333
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study endotoxin release from two strains of Escherichia coli after exposure to two repeated doses of cefuroxime in an in vitro kinetic model. Methods: Cefuroxime in concentrations simulating human pharmacokinetics was added to the bacterial solution with a repeated dose after 12 h. In another experiment, tobramycin was given concomitantly with the second dose of cefuroxime. Samples for viable counts and endotoxin analyses were drawn before the addition of antibiotics and at 2 and 4 h after each dose. Results: The propensity to release endotoxin, expressed as log10 endotoxin release (EU)/log10 killed bacteria, was higher after the second than after the first dose, 0.80 ± 0.04 and 0.65 ± 0.01, respectively, in the ATCC strain and 0.80 ± 0.04 and 0.65 ± 0.02, respectively, in the clinical strain (P < 0.001). Endotoxin was released earlier after the second dose (P < 0.001). Addition of tobramycin at the second dose reduced the endotoxin release in comparison with that of cefuroxime alone (P < 0.001). Conclusions: The propensity to liberate endotoxin is higher after the second dose of cefuroxime than after the first, resulting in a higher release of endotoxin than expected from bacterial count. The release after the second dose can be reduced by the addition of tobramycin.
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