To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.

Staphylococcus epidermidis biofilm formation on polymer surfaces is considered a major pathogenicity factor in foreign-body-associated infections. Previously, the 148 kDa autolysin AtlE from S. epidermidis, which is involved in the initial attachment of the cells to polymer surfaces and also binds to the extracellular matrix protein vitronectin, was characterized. Here, the characterization of a novel autolysin/adhesin (Aae) in S. epidermidis is described. Aae was identified as a 35 kDa surface-associated protein that has bacteriolytic activity and binds vitronectin. Its N-terminal amino acid sequence was determined and the respective gene, aae, was cloned. DNA-sequence analysis revealed that aae encodes a deduced protein of 324 amino acids with a predicted molecular mass of 35 kDa. Aae contains three repetitive sequences in its N-terminal portion. These repeats comprise features of a putative peptidoglycan binding domain (LysM domain) found in a number of enzymes involved in cell-wall metabolism and also in some adhesins. Expression of aae by Escherichia coli and subsequent analysis revealed that Aae possesses bacteriolytic activity and adhesive properties. The interaction of Aae with fibrinogen, fibronectin and vitronectin was found to be dose-dependent and saturable and to occur with high affinity, by using the real-time Biomolecular Interaction Analysis (BIA). Aae binds to the Aa-and Bb-chains of fibrinogen and to the 29 kDa N-terminal fragment of fibronectin. In conclusion, Aae is a surface-associated protein with bacteriolytic and adhesive properties representing a new member of the staphylococcal autolysin/adhesins potentially involved in colonization.

We describe the first case of a Kocuria rhizophila infection in a boy with methylmalonic aciduria. A single clone was isolated from blood samples drawn through a port system and from peripheral veins during septic episodes within a 2-year period. K. rhizophila expands the emerging number of “micrococci” considered to be etiologically relevant.

Platelets bind to Candida albicans, the major cause of candidiasis. But in contrast to other microorganisms the fungus does not aggregate platelets. Gliotoxin (GT), which possesses immunosuppressive properties, is produced by various fungi, including the opportunistic pathogens Aspergillus fumigatus and C. albicans . Its mode of action involves the formation of mixed disulfides with host proteins. Disulfide exchanges play an important role in platelet activation. Therefore, the effect of C. albicans and GT on platelet function was tested. C. albicans yeast cells (5,000-10,000 cells/microl) and GT, in pathophysiologically relevant concentrations (0.05-0.5 microM), inhibited platelet fibrinogen binding, anti gp IIb/IIIa antibody PAC-1 binding, aggregation and procoagulant activity in a dose-dependent manner. Alpha granule release, measured via CD62P surface expression, was not affected. Addition of reduced glutathione partially counteracted the effect of C. albicans and GT on platelet fibrinogen binding and platelet aggregation. The C. albicans metabolite GT features antithrombotic properties in addition to its immunosuppressive functions. Since treatment with reduced glutathione partially counteracted the inhibitory effect of C. albicans yeast cells and GT on platelet fibrinogen binding, the antithrombotic activity is likely to depend on the disulfide bridge of this mycotoxin. GT production by C. albicans could contribute to its survival in the blood stream during vascular infections. The knowledge of the underlying mechanisms of the antithrombotic properties might help to treat fungal infections as well as thrombosis.

Staphylococcus aureus produces and secretes a protein, extracellular fibrinogen binding protein (Efb), which contributes to virulence in wound infection. We have previously shown that Efb is a potent inhibitor of platelet function in vitro. We confirm here that this is also the case in vivo. Pre-treatment with Efb resulted in a significant prolongation of bleeding time in a mouse model. Furthermore, Efb was capable of rescuing animals from death caused by the administration of potent platelet agonists. This antiplatelet effect may explain the retardation of wound healing associated with Efb in S. aureus wound infections. These results are important not only in terms of understanding S. aureus pathogenesis, and consequently identifying new treatment strategies, but also with regard to the development of potential, novel antiplatelet agents for the prevention of thrombosis.