ABSTRACT
Analysing culture supernatants of yeast and hyphal cells of Candida albicans, we found two close homologues of pathogenesis-related (PR-) 1 proteins, Rbe1p and Rbt4p, in the secretome. Due to sequence homology, three additional, yet not characterized open reading frames, ORF19.6200, ORF19.2787 and ORF19.2336, together with RBE1 and RBT4 were assigned to a novel family of CaPRY proteins. In a Δrbe1/Δrbt4 deletion strain, genome-wide transcriptional analysis revealed differential transcription of only a limited set of genes implicated in virulence and oxidative stress response. Single deletion of RBE1 or RBT4 in a clinical C. albicans isolate resulted in a moderate but significant attenuation in virulence in a mouse model for disseminated candidiasis. However, a synergistic effect was observed in a Δrbe1/Δrbt4 double deletion strain, where virulence was strongly affected. Remarkably, transcription of RBT4 and RBE1 was each upregulated in blastospores of Δrbe1 or hyphae of Δrbt4 deletion strains respectively, indicating functional complementation thereby compensating a potential virulence defect in the single deletion strains. Furthermore, the double deletion strain showed increased sensitivity to attack by polymorphonuclear leucocytes. Therefore, the crucial contribution of both C. albicans pathogenesis-related proteins to virulence might be vested in protection against phagocyte attack.
Subject(s)
Candida albicans/genetics , Candida albicans/pathogenicity , Fungal Proteins/genetics , Fungal Proteins/metabolism , Amino Acid Sequence , Animals , Candida albicans/metabolism , DNA, Fungal/genetics , Gene Expression Profiling , Gene Expression Regulation, Fungal , Genome, Fungal , Mice , Molecular Sequence Data , Open Reading Frames , Oxidative Stress/genetics , Phenotype , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , Sequence Alignment , Sequence Deletion , Virulence/geneticsABSTRACT
OBJECTIVES: To investigate the age-related outcome of peripheral thrombolysis and determine for which patient group this treatment is worthwhile. DESIGN AND METHODS: A combined retrospective and prospective analysis of consecutive patients undergoing thrombolysis for acute lower-limb ischaemia was made with respect to age-related outcome and other risk factors. RESULTS: One hundred and two patients underwent thrombolysis for acute limb ischaemia. In the under 60 age group there was a 40% amputation rate. Seventy-three per cent of this group smoked. In the over 80 age group, the amputation rate was 15% and only 8% were smokers. CONCLUSION: Advancing age is not an adverse risk factor for thrombolysis which appears to be safe and effective in this patient group. There is a high incidence of smoking in the younger age group (< 60 years), in whom failed thrombolysis frequently leads to amputation.
