ABSTRACT
Staphylococcus pseudintermedius is an important pathogen responsible for infections in dogs and in humans. The emergence and dissemination of methicillin-resistant S. pseudintermedius (MRSP) and the multidrug resistance frequently seen in this species make difficult the treatment of these pathogens. The cefoxitin disk is widely used as a marker of methicillin resistance mediated by the mecA gene in Staphylococcus aureus and other staphylococcal species; however, it is not useful to detect ß-lactam resistance of MRSP in clinical microbiology laboratories. The purpose of this study was to elucidate the molecular bases of the dissociated phenotype between oxacillin and cefoxitin antibiotics. By using a combinatorial approach that included the Penicillin-Binding Proteins' (PBP) profile, their affinity for different ß-lactam antibiotics and the analyses of PBPs' sequence, we provide evidence that PBP4 showed still affinity for its target cefoxitin, impairing its phenotypic resistant detection in MRSP. Together, these findings provide evidence that S. pseudintermedius PBP4 is directly associated with the dissociated oxacillin and cefoxitin phenotype.
ABSTRACT
The nuclear receptor coactivator RAC3 plays important roles in many biological processes and tumorigenesis. We found that RAC3 is over-expressed in human chronic myeloid leukemia cells K562, which are normally resistant to TRAIL-induced apoptosis. RAC3 down-regulation by siRNA rendered these cells sensitive to TRAIL-induced cell death. In addition to the up-regulation of TRAIL receptors, the process involves Bid, caspases and PARP activation, loss of mitochondrial membrane potential, and release of AIF, cytochrome c and Smac/DIABLO to the cytoplasm. We conclude that RAC3 is required for TRAIL resistance and that this anti-apoptotic function is independent of its role in hormone receptor signaling.