Charlotte Linde

Karolinska Institutet, Solna, Stockholm, Sweden

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Publications (5)20.64 Total impact

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    ABSTRACT: Statin treatment has been associated with a beneficial outcome on respiratory tract infections. In addition, previous in vitro and in vivo experiments have indicated favorable effects of statins in bacterial infections. The aim of the present study was to elucidate possible antibacterial effects of statins against primary pathogens of the respiratory tract. MIC-values for simvastatin, fluvastatin and pravastatin against S. pneumoniae, M. catarrhalis and H. influenzae were determined by traditional antibacterial assays. A BioScreen instrument was used to monitor effects of statins on bacterial growth and to assess possible synergistic effects with penicillin. Bacterial growth in whole blood and serum from healthy volunteers before and after a single dose of simvastatin, fluvastatin and penicillin (positive control) was determined using a blood culture system (BactAlert). The MIC-value for simvastatin against S pneumoniae and M catarrhalis was 15 µg/mL (36 mmol/L). Fluvastatin and Pravastatin showed no antibacterial effect in concentrations up to 100 µg/mL (230 µmol/L). Statins did not affect growth or viability of H influenzae. Single doses of statins given to healthy volunteers did not affect growth of pneumococci, whereas penicillin efficiently killed all bacteria. Simvastatin at high concentrations 15 µg/mL (36 µmol/L) rapidly kills S pneumoniae and M catarrhalis. However, these concentrations by far exceed the concentrations detected in human blood during simvastatin therapy (1-15 nmol/L) and single doses of statins given to healthy volunteers did not improve antibacterial effects of whole blood. Thus, a direct bactericidal effect of statins in vivo is probably not the mechanism behind the observed beneficial effect of statins against various infections.
    PLoS ONE 08/2011; 6(8):e24394. DOI:10.1371/journal.pone.0024394 · 3.53 Impact Factor
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    ABSTRACT: Previously it was shown that the antimicrobial protein granulysin possesses potent membranolytic activity against Mycobacterium tuberculosis. Here we demonstrate that granF2 and G13, which are two short synthetic peptides derived from granulysin, inhibited the in vitro growth of clinical isolates of both multidrug resistant and drug susceptible strains of M. tuberculosis. Importantly, a particularly high activity against multidrug resistant M. tuberculosis correlated with a reduced growth rate compared to drug susceptible strains. A synergistic antibacterial effect of granF2 was further observed in combination with ethambutol, a compound with a documented effect on cell wall permeability. This finding suggests that granF2 and ethambutol exert their functions at different levels of the mycobacterial surface. Upon infection of macrophages in vitro, granF2 but not G13 efficiently reduced the intracellular growth of multidrug resistant M. tuberculosis in the presence of the pore-forming protein streptolysin O. The apoptotic function of granF2 apparently promoted destruction of host cells whereby the peptide gained access to and killed intracellular bacteria. Thus, a cost of resistance and a subsequent reduced fitness, measured as decreased growth among multidrug resistant strains of M. tuberculosis, could be associated with increased susceptibility to natural immune defense mechanisms, such as antimicrobial peptides of granulysin. However, a robust cell wall and the membrane of cells still provide physical shelter for the bacteria that may spare sensitive M. tuberculosis stains from being killed.
    Microbes and Infection 08/2006; 8(8):1985-93. DOI:10.1016/j.micinf.2006.02.030 · 2.73 Impact Factor
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    ABSTRACT: Granulysin and NK-lysin are homologous bactericidal proteins with a moderate residue identity (35%), both of which have antimycobacterial activity. Short loop peptides derived from the antimycobacterial domains of granulysin, NK-lysin, and a putative chicken NK-lysin were examined and shown to have comparable antimycobacterial but variable Escherichia coli activities. The known structure of the NK-lysin loop peptide was used to predict the structure of the equivalent peptides of granulysin and chicken NK-lysin by homology modeling. The last two adopted a secondary structure almost identical to that of NK-lysin. All three peptides form very similar three-dimensional (3-D) architectures in which the important basic residues assume the same positions in space. The basic residues in granulysin are arginine, while those in NK-lysin and chicken NK-lysin are a mixture of arginine and lysine. We altered the ratio of arginine to lysine in the granulysin fragment to examine the importance of basic residues for antimycobacterial activity. The alteration of the amino acids reduced the activity against E. coli to a larger extent than that against Mycobacterium smegmatis. In granulysin, the arginines in the loop structure are not crucial for antimycobacterial activity but are important for cytotoxicity. We suggest that the antibacterial domains of the related proteins granulysin, NK-lysin, and chicken NK-lysin have conserved their 3-D structure and their function against mycobacteria.
    Infection and Immunity 11/2005; 73(10):6332-9. DOI:10.1128/IAI.73.10.6332-6339.2005 · 4.16 Impact Factor
  • C. M. A. Linde, S E Hoffner, E Refai, M Andersson
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    ABSTRACT: We have investigated the in vitro activity of antimicrobial peptides against Mycobacterium tuberculosis using a radiometric method and cfu determinations. PR-39, a proline-arginine-rich antibacterial peptide from porcine leucocytes, was found to be active against drug-susceptible as well as multi-drug-resistant (MDR) clinical isolates of M. tuberculosis. The activity of PR-39 was concentration dependent, with 80% growth inhibition of M. tuberculosis H37Rv at 50 mg/L. The MDR M. tuberculosis strains E1380/94 and P34/95 were less susceptible to PR-39, with 39 and 49% growth inhibition at 50 mg/L peptide, respectively, suggesting a lower susceptibility than strain H37Rv and drug-susceptible clinical isolates. Reduction of counts of M. tuberculosis H37Rv and the MDR M. tuberculosis strain E1380/94 by PR-39 indicated that the growth inhibition seen in the radiometric assay is due to a mycobactericidal effect of the peptide. These observations suggest that antimicrobial peptides may play an important role in host defence against MDR M. tuberculosis.
    Journal of Antimicrobial Chemotherapy 06/2001; 47(5):575-80. DOI:10.1093/jac/47.5.575 · 5.44 Impact Factor
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    ABSTRACT: NK-lysin and granulysin are homologous cationic anti-bacterial peptides produced by pig and human cytolytic lymphocytes, respectively. The solution structure of NK-lysin comprises five amphipathic alpha-helices. To investigate the properties of a helix-loop-helix region postulated to be a membrane-docking part of NK-lysin, we synthesized 22- and 29-residue peptides reproducing this region for both NK-lysin and granulysin. CD spectroscopy of the synthetic peptides in a liposomal solution showed spectra typical of alpha-helical peptides. The peptides were active against Gram-positive and Gram-negative bacteria, with the two NK-lysin peptides showing higher anti-bacterial activities than the two from granulysin. One NK-lysin peptide was active against Pseudomonas aeruginosa and Staphylococcus aureus, two organisms against which NK-lysin is inactive. Granulysin peptides were inactive against these bacteria, in contrast with granulysin, which is known to be active against them. Both NK-lysin and all synthetic analogues killed Mycobacterium tuberculosis and K562 tumour cells, but did not display haemolytic activity. These results identify a potent anti-mycobacterial domain in NK-lysin and granulysin consisting of a 22-residue (helix 3) sequence plus a disulphide-constrained loop.
    Biochemical Journal 01/2000; 344 Pt 3:845-9. DOI:10.1042/0264-6021:3440845 · 4.78 Impact Factor

Publication Stats

137 Citations
20.64 Total Impact Points


  • 2001–2011
    • Karolinska Institutet
      • Department of Medical Biochemistry and Biophysics
      Solna, Stockholm, Sweden