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Sökning: WFRF:(Parham P) > (2008-2009)

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  • Johansson, Linda, et al. (författare)
  • Cathelicidin LL-37 in Severe Streptococcus pyogenes Soft Tissue Infections in Humans
  • 2008
  • Ingår i: Infection and Immunity. - : American Society for Microbiology. - 1098-5522. ; 76:8, s. 3399-3404
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe soft tissue infections, such as necrotizing fasciitis and severe cellulitis, caused by group A streptococcus (GAS) are rapidly progressing life-threatening infections characterized by massive bacterial load in the tissue even late after onset of infection. Antimicrobial peptides are important components of the innate host defence and cathelicidins have been shown to protect against murine necrotic skin infection caused by GAS. However, the streptococcal cysteine protease SpeB has been demonstrated to proteolytically inactivate the human cathelicidin LL-37 in vitro. Here we have investigated the expression of LL-37 and its interaction with GAS and SpeB during acute severe soft tissue infections by analyses of patient tissue biopsies. The results showed high amounts of LL-37, both the proform (hCAP18) and the mature peptide, present in the tissue. Confocal microscopy identified neutrophils as the main source of the peptide. A distinct co-localization between the bacteria and LL-37 could be noted, and bacterial load showed a positive correlation to the LL-37 levels. Areas with high LL-37 levels coincided with areas with high amounts of SpeB. Confocal microscopy confirmed a strong co-localization of GAS, SpeB and LL-37 at the bacterial surface. Taken together the findings of this study provides in vivo support that SpeB-mediated inactivation of LL-37 at the streptococcal surface represent a bacterial resistance mechanism at the infected tissue site in patients with severe GAS tissue infections.
  • Sendi, Parham, et al. (författare)
  • Bacterial phenotype variants in group B streptococcal toxic shock syndrome
  • 2009
  • Ingår i: Emerging Infectious Diseases. - 1080-6040 .- 1080-6059. ; 15:2, s. 223-232
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted genetic and functional analyses of isolates from a patient with group B streptococcal (GBS) necrotizing fasciitis and toxic shock syndrome. Tissue cultures simultaneously showed colonies with high hemolysis (HH) and low hemolysis (LH). Conversely, the HH and LH variants exhibited low capsule (LC) and high capsule (HC) expression, respectively. Molecular analysis demonstrated that the 2 GBS variants were of the same clonal origin. Genetic analysis found a 3-bp deletion in the covR gene of the HH/LC variant. Functionally, this isolate was associated with an increased growth rate in vitro and with higher interleukin-8 induction. However, in whole blood, opsonophagocytic and intracellular killing assays, the LH/HC phenotype demonstrated higher resistance to host phagocytic killing. In a murine model, LH/HC resulted in higher levels of bacteremia and increased host mortality rate. These findings demonstrate differences in GBS isolates of the same clonal origin but varying phenotypes.
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  • Resultat 1-2 av 2

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