RESUMEN
BACKGROUND: Chronic rhinosinusitis (CRS) has been linked to the gram-positive bacteria Staphylococcus aureus (S. aureus) in its biofilm or intracellular forms. Recent evidence suggests that S. aureus also exists in a small-colony variant (SCV) form as a mechanism of altering its virulence capabilities. The aim of this study was to investigate the presence of SCVs in sinonasal mucosa of CRS patients and whether the phenomenon of phenotype switching can be applied to intracellular epithelial infections. METHODS: Sinonasal specimens were examined for the presence of intramucosal S. aureus and characterized to the strain level. An airway epithelial cell culture infection model was utilized to investigate whether bacteria were capable of alterations in virulence phenotype. RESULTS: Intramucosal organisms harvested from sinonasal biopsies demonstrate phenotypic growth patterns and lack of coagulase activity consistent with SCVs. Intracellular infection of airway epithelial cell cultures with S. aureus led to decreased secretion of enterotoxins and phenotypic growth alterations consistent with SCVs. CONCLUSIONS: Regulation of S. aureus virulence factors is a dynamic process, and exposure to the intracellular environment appears to provide the necessary conditions to enable these alterations in an attempt for the bacterium to survive and persist within host tissues. Further work is required to ascertain whether SCVs in CRS hold a clinically relevant pathogenic role in recalcitrant disease.
Asunto(s)
Mucosa Nasal/microbiología , Rinitis/microbiología , Sinusitis/microbiología , Infecciones Estafilocócicas/microbiología , Adulto , Femenino , Humanos , Masculino , Fenotipo , Staphylococcus aureus/crecimiento & desarrolloRESUMEN
Mitotic microtubule (MT)-targeting drugs are widely used to treat cancer. The GTPase Ran regulates multiple processes, including mitotic spindle assembly, spindle pole formation and MT dynamics; Ran activity is therefore essential to formation of a functional mitotic apparatus. The RanBP1 protein, which binds Ran and regulates its interaction with effectors, is overexpressed in many cancer types. Several observations indicate that RanBP1 contributes to regulate the function of the mitotic apparatus: RanBP1 inactivation yields hyperstable MTs and induces apoptosis during mitosis, reminiscent of the effects of the MT-stabilizing drug taxol. Here we have investigated the influence of RanBP1 on spontaneous and taxol-induced apoptosis in transformed cells. We report that RanBP1 downregulation by RNA interference activates apoptosis in several transformed cell lines regardless of their p53 status, but not in the caspase-3-defective MCF-7 breast cancer cell line. Furthermore, RanBP1-interfered cells show an increased apoptotic response to taxol compared to their counterpart with normal or high RanBP1 levels, and this response is caspase-3 dependent. These results indicate that RanBP1 can modulate the outcome of MT-targeting therapeutic protocols.