RESUMO
The aim of this study was to compare the quantitative susceptibility of methicillin-resistant and -susceptible Staphylococcus aureus (MRSA and MSSA) strains from three European countries to nine antistaphylococcal agents. The antibiotic susceptibility of 274 MRSA and 284 MSSA strains from Hungary, Austria and macedonia was tested by the broth microdilution method. The clonal relationship of strains was determined by pulsed-field gel electrophoresis. Intermediate susceptibility to vancomycin appeared in Macedonian MRSA strains. Macedonian MRSA strains had high-level amikacin and gentamicin resistance. MSSA strains generally were susceptible to all drugs at minimum inhibitory concentrations (MIC(50)) except for gentamicin resistance in Macedonian strains. In Hungary and Austria a common antibiotic resistance phenotype of MRSA predominated, while in macedonia three other phenotypes were also prevalent. Geographical differences in the resistance of S. aureus are still high. Since resistance levels of MRSA and MSSA strains differ extensively, they should be considered separately for antibiotic resistance analysis.
Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Áustria , Farmacorresistência Bacteriana Múltipla/genética , Hungria , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Fenótipo , Reação em Cadeia da Polimerase , República da Macedônia do Norte , Staphylococcus aureus/genéticaRESUMO
TNF-alpha converting enzyme (TACE) is the protease responsible for processing proTNF from the 26-kDa membrane-anchored precursor to the secreted 17-kDa TNF-alpha. We show here that a deletion mutant of TACE (dTACE), lacking the pro and catalytic domains of the protease, acts as a dominant negative for proTNF processing in transfected HEK293 cells. We used the same system to test the effect of dTACE on TNFRII processing. Overexpression of dTACE with TNFRII resulted in >80% inhibition of TNFRII shedding. Although significant inhibition of TNF-alpha and TNFRII shedding was achieved with dTACE, we could not detect a cell surface accumulation of the noncleaved substrates above that observed in the absence of dTACE. Our results suggest that TNFRII is a substrate for TACE, and that dTACE is capable of interfering with the function of endogenous TACE, either by binding and sequestering TACE substrates via the disintegrin domain, transmembrane domain, or cytoplasmic tail, or by some other mechanism that has yet to be determined.