Examinando por Autor "Kerns, Morgan E."
Mostrando 1 - 2 de 2
Resultados por página
Opciones de ordenación
Publicación Acceso abierto ERG2 and ERG24 are required for normal vacuolar physiology as well as candida albicans pathogenicity in a murine model of disseminated but not vaginal candidiasis.(Estados Unidos: Eukaryotic Cell, 2015., 2019-10-01) Luna Tapia, Arturo; Peters, Brian M.; Eberle, Karen E.; Kerns, Morgan E.; Palmer, Glen E.; Foster, Timothy P.; Marrero, Luis; Noverr, Mairi C.; Fidel , Paul L.; American Society for Microbiology.Several important classes of antifungal agents, including the azoles, act by blocking ergosterol biosynthesis. It was recently reported that the azoles cause massive disruption of the fungal vacuole in the prevalent human pathogen Candida albicans. This is significant because normal vacuolar function is required to support C. albicans pathogenicity. This study examined the impact of the morpholine antifungals, which inhibit later steps of ergosterol biosynthesis, on C. albicans vacuolar integrity. It was found that overexpression of either the ERG2 or ERG24 gene, encoding C-8 sterol isomerase or C-14 sterol reductase, respectively, suppressed C. albicans sensitivity to the morpholines. In addition, both erg2 / and erg24 / mutants were hypersensitive to the morpholines. These data are consistent with the antifungal activity of the morpholines depending upon the simultaneous inhibition of both Erg2p and Erg24p. The vacuoles within both erg2 / and erg24 / C. albicans strains exhibited an aberrant morphology and accumulated large quantities of the weak base quinacrine, indicating enhanced vacuolar acidification compared with that of control strains. Both erg mutants exhibited significant defects in polarized hyphal growth and were avirulent in a mouse model of disseminated candidiasis. Surprisingly, in a mouse model of vaginal candidiasis, both mutants colonized mice at high levels and induced a pathogenic response similar to that with the controls. Thus, while targeting Erg2p or Erg24p alone could provide a potentially efficacious therapy for disseminated candidiasis, it may not be an effective strategy to treat vaginal infections. The potential value of drugs targeting these enzymes as adjunctive therapies is discussed.Publicación Acceso abierto Trafficking through the late endosome significantly impacts candida albicans tolerance of the azole antifungals.(Estados Unidos: Antimicrobial Agents and Chemotherapy , 2015., 2019-10-02) Luna Tapia, Arturo; Kerns, Morgan E.; Jursic, Branko S.; Eberle, Karen E.; Palmer, Glen E.; American Society for Microbiology.The purpose of this study was to characterize the effects of azole treatment upon the integrity of the Candida albicans vacuole and to determine whether, in turn, vacuolar trafficking influences azole susceptibility. Profound fragmentation of the C. albicans vacuole can be observed as an early consequence of azole treatment, and it precedes significant growth inhibition. In addition, a C. albicans vps21/ mutant, blocked in membrane trafficking through the late endosomal prevacuolar compartment (PVC), is able to grow significantly more than the wild type in the presence of several azole antifungals under standard susceptibility testing conditions. F.