Contribution of Streptococcus anginosus to Infections Caused by Groups C and G Streptococci, Southern India

This neglected pathogen causes a large portion of these infections

A liver fibrosis cocktail? Psoriasis, methotrexate and genetic hemochromatosis

BACKGROUND: Pathologists are often faced with the dilemma of whether to recommend continuation of methotrexate therapy for psoriasis within the context of an existing pro-fibrogenic risk factor, in this instance, patients with genetic hemochromatosis. CASE PRESENTATIONS: We describe our experience with two male psoriatic patients (A and B) on long term methotrexate therapy (cumulative dose A = 1.56 gms and B = 7.88 gms) with hetero- (A) and homozygous (B) genetic hemochromatosis. These patients liver function were monitored with routine biochemical profiling; apart from mild perivenular fibrosis in one patient (B), significant liver fibrosis was not identified in either patient with multiple interval percutaneous liver biopsies; in the latter instance this patient (B) had an additional risk factor of partiality to alcohol. CONCLUSION: We conclude that methotrexate therapy is relatively safe in patients with genetic hemochromatosis, with no other risk factor, but caution that the risk of fibrosis be monitored, preferably by non-invasive techniques, or by liver biopsy

Streptococcal protein FOG, a novel matrix adhesin interacting with collagen I in vivo.

Group G streptococcus (GGS) is a human pathogen of emerging clinical significance. It causes skin and soft tissue infections, occasionally resulting in life-threatening conditions such as sepsis and necrotizing fasciitis. We recently identified FOG, a novel surface protein of GGS with fibrinogen binding and immune evasion properties. Here we investigated the role of FOG in streptococcal primary adhesion to host tissue. A FOG-expressing clinical isolate adhered more efficiently to human skin biopsies ex vivo and to the murine dermis in vivo than a FOG-deficient strain. Scanning and transmission electron microscopy of skin specimens exhibited that this property was assigned to the ability of FOG to interact with collagen I, a major interstitial component of the dermis. Overlay experiments with human skin extracts and radiolabeled FOG followed by matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis identified both the alpha1- and alpha2-chains of collagen I as targets for FOG. Transmission electron microscopy of the molecular complexes revealed thread-like FOG molecules binding via their NH2 termini to distinct sites on collagen I monomers and fibrils. The results demonstrate that FOG is important for GGS adhesion in vivo, implying a pathogenic role for this surface protein

Group G streptococcal IgG binding molecules FOG and protein G have different impacts on opsonization by C1q

Recent epidemiological data on diseases caused by beta-hemolytic streptococci belonging to Lancefield group C and G ( GCS, GGS) underline that they are an emerging threat to human health. Among various virulence factors expressed by GCS and GGS isolates from human infections, M and M-like proteins are considered important because of their anti-phagocytic activity. In addition, protein G has been implicated in the accumulation of IgG on the bacterial surface through non-immune binding. The function of this interaction, however, is still unknown. Using isogenic mutants lacking protein G or the M-like protein FOG ( group G streptococci), respectively, we could show that FOG contributes substantially to IgG binding. A detailed characterization of the interaction between IgG and FOG revealed its ability to bind the Fc region of human IgG and its binding to the subclasses IgG1, IgG2, and IgG4. FOG was also found to bind IgG of several animal species. Surface plasmon resonance measurements indicate a high affinity to human IgG with a dissociation constant of 2.4 pM. The binding site was localized in a central motif of FOG. It has long been speculated about anti-opsonic functions of streptococcal Fc-binding proteins. The presented data for the first time provide evidence and, furthermore, indicate functional differences between protein G and FOG. By obstructing the interaction between IgG and C1q, protein G prevented recognition by the classical pathway of the complement system. In contrast, IgG that was bound to FOG remained capable of binding C1q, an effect that may have important consequences in the pathogenesis of GGS infections