Interaction between group A streptococci and the plasmin(ogen) system promotes virulence in a mouse skin infection model.
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Group A streptococci are capable of acquiring a surface-associated, unregulatable plasmin-like enzymatic activity when incubated in human plasma. The effect of this enzymatic activity on virulence of group A isolate CS101 was examined in a mouse skin infection model. Initial studies demonstrated enhanced virulence for bacteria preincubated in human plasma but not in plasminogen-depleted plasma. A direct correlation between surface-associated enzymatic activity and virulence was not observed; however, an association between virulence and the assembly of a surface-associated plasminogen activator that could activate mouse plasminogen was noted. This activity enhanced virulence in wild type but not in plg-/- plasminogen-deficient mice. These results support the hypothesis that acquisition of a surface-associated plasmin(ogen)-dependent enzymatic activity can contribute to the virulence of group A streptococcal invasive infections. (+info)
Activity of gatifloxacin compared to those of five other quinolones versus aerobic and anaerobic isolates from skin and soft tissue samples of human and animal bite wound infections.
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The activity of gatifloxacin against 308 aerobes and 112 anaerobes isolated from bite wound infections was studied. Gatifloxacin was active at +info)
Extradigestive manifestations of Helicobacter pylori gastric infection.
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In the past year, several studies have been carried out on the association between Helicobacter pylori infection and a miscellany of extradigestive diseases, such as cardiovascular, immunological, and various other pathologies. In particular, a higher prevalence of H pylori infection in patients affected by ischaemic heart disease has been described and there is growing evidence for an association between H pylori and some autoimmune diseases. Moreover, recent studies have shown that various helicobacter species have been detected in human bile; if confirmed, this finding could revise the diagnostic and therapeutic approach to diseases of the biliary tract. (+info)
A two-component regulatory system, CsrR-CsrS, represses expression of three Streptococcus pyogenes virulence factors, hyaluronic acid capsule, streptolysin S, and pyrogenic exotoxin B.
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Certain Tn916 insertions in the chromosome of an M1-type, nonmucoid Streptococcus pyogenes isolate (MGAS166) were previously shown to result in stable mucoidy with increased expression of the capsular synthetic genes. The transposon insertions in these strains are directly upstream of an apparent operon encoding a two-component regulatory system, designated csrR-csrS. Compared with MGAS166, these mucoid mutants are more hemolytic and cause significantly more tissue damage in a murine model of skin infection. To extend these observations, we constructed an in-frame deletion in the gene encoding the response regulator, csrR, and we evaluated the expression of other known S. pyogenes virulence factors. We discovered that csrR mutants have enhanced transcription of sagA, a gene associated with streptolysin S (SLS) and speB, the gene encoding pyrogenic exotoxin B (SpeB). The mutants also express substantially higher SLS activity and SpeB antigen in late-exponential-phase cultures. There is no change in expression of emm, scpA, sic, or cpa (genes encoding other S. pyogenes virulence factors). CsrR- strains but not the wild-type parental strain produce necrotizing lesions in a mouse model of subcutaneous infection. A double mutant with deletions in both csrR and the capsular synthesis genes caused fewer and smaller necrotic skin lesions than the csrR mutants. However, this nonmucoid csrR strain was more likely than the wild type to yield necrotic lesions, suggesting that mucoidy contributes to virulence in this model of infection but that there are other csrR-regulated factors involved in the production of necrotic lesions. (+info)
Critical role of neutrophils for the generation of psoriasiform skin lesions in flaky skin mice.
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Although T cell dysregulation is thought to underlie the pathogenesis of psoriasis, prominent infiltration and microabscess formation by neutrophils is a distinctive hallmark feature of this common disorder. The exact role of neutrophils in the pathogenesis of psoriasiform alterations in vivo, however, is unknown. Similar to human psoriasis, flaky skin mice (fsn/fsn) revealed a prominent infiltrate of neutrophils, and microabscesses within the hyperproliferative epidermis were associated with de novo expression of intercellular adhesion molecule-1. Intraperitoneal injection with the neutrophil-depleting RB6-8C5 monoclonal antibody (anti-Ly-6G) resulted in a dramatic reduction of the epidermal thickness by 58% compared with isotype-treated animals (p < 0.001). In addition, epidermal microabscesses were conspicuously absent (p < 0.001), and cutaneous neutrophils and T cells, but not mast cells or dendritic cells, were markedly reduced in anti-Ly-6G-treated mice. Proinflammatory cytokines, including tumor necrosis factor alpha and interleukin-1, were also downregulated. Therapeutic effects occurred as early as 4 d after beginning of treatment. Wildtype skin was not affected. When the integrin alphaMbeta2 (CD11b/CD18), which mediates neutrophil localization through binding to intercellular adhesion molecule-1, was blocked in vivo with the M1/70 monoclonal antibody, the epidermal thickness was reduced by 31% (p < 0.002), and neutrophil and T cell accumulation was diminished compared with control animals. Likewise, treatment of fsn/fsn mice with the MP1-22E9 monoclonal antibody neutralizing granulocyte macrophage-colony stimulating factor, a cytokine stimulating neutrophils by upregulating alphaMbeta2, resulted in significant reduction of inflammation and acanthosis by 30% (p < 0.003). These results demonstrate a critical pathogenic role of neutrophils for hyperproliferative inflammatory lesions in fsn/fsn mice, suggesting that blocking neutrophil function may have therapeutic benefit in some human skin disorders. (+info)
Cell-mediated immune responses in Staphylococcus aureus infections in mice.
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Delayed hypersensitivity to staphylococcal antigens was shown in mice repeatedly infected with Staphylococcus aureus. It was characterized by footpad swelling at 48 hours with a mononuclear cell infiltrate and could be transferred to non-infected recipients by T lymphocytes from infected animals, but not by serum. Recipients of immune T cells produced very severe necrotic lesions when challenged with staphylococci. This was in contrast to the protection against necrosis in recipients afforded by serum from infected donors. When both serum and cells were transferred into the same mouse the humoral effects overshadowed or perhaps inhibited those mediated by cells with resultant protection against staphylococcal dermonecrosis. (+info)
Type 1 diabetes mellitus masking primary antibody deficiency.
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A patient with a history of recurrent cutaneous and pulmonary infections, nephrotic syndrome, and an established diagnosis of type 1 diabetes was found to have unsuspected and unrecognised primary immunodeficiency. On review of the case, previous investigations pointed to the correct diagnosis over 10 years earlier. This combination of diagnoses has not previously been reported. The patient is now well on replacement intravenous immunoglobulin therapy, urinary loss of IgG having been specifically excluded before treatment. This case highlights how antibody deficiency can easily be missed despite an obvious infection history unless results are interpreted carefully and in context. (+info)
Comparative efficacy of 5 days of dirithromycin and 7 days of erythromycin in skin and soft tissue infections.
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We investigated the comparative efficacy and safety of dirithromycin and erythromycin in the treatment of skin and soft tissue infections in this double-blind, randomized, multicentre study, in which 439 patients were randomized to treatment with dirithromycin (500 mg daily for 5 days) or erythromycin (250 mg every 6 h for 7 days). All randomized patients were included in the termination analysis, which showed that 187 of 220 (85.0%) dirithromycin recipients and 177 of 219 (80.8%) erythromycin recipients were clinically cured or improved (95% confidence interval (CI) -3.0% to +11.4%). In the termination analysis of the 211 bacteriologically evaluable patients, clinical cure or improvement occurred in 83 of 100 (83%) dirithromycin recipients and in 89 of 111 (80.2%) erythromycin recipients (95% CI -7.8% to +13.4%), and bacteriological eradication occurred in 85 of 100 (85%) and 89 of 111 (80.2%), respectively. Adverse events were similar in incidence and nature between the two groups, except that there was less nausea with dirithromycin (3.6% versus 8.2%; P = 0.042). Ten of 220 (4.5%) dirithromycin recipients and 27 of 219 (12.3%) erythromycin recipients returned >20% of their prescribed medication (P = 0.033). In the treatment of skin and soft tissue infections, dirithromycin (500 mg daily for 5 days) was comparable in efficacy to, and caused significantly less nausea than, erythromycin (250 mg every 6 h for 7 days). Compliance with the dirithromycin regimen was superior to that with the erythromycin regimen. (+info)