Examinando por Autor "Peters, Brian M."
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Publicación Acceso abierto An azole tolerant endosomal trafficking mutant of Candida albicans is susceptible to azole treatment in a mouse model of vaginal candidiasis.(Estados Unidos Antimicrobial Agents and Chemotherapy, 2017., 2019-09-24) Peters, Brian M.; Luna Tapia, Arturo; Tournu, Héléne; Rybak, Jeffrey M.; Rogers, David P.; Palmer, Glen E.; American Society for Microbiology.We recently reported that a Candida albicans endosomal trafficking mutant continues to grow after treatment with the azole antifungals. Herein, we report that the vps21Δ/Δ mutant does not have a survival advantage over wild-type isolates after fluconazole treatment in a mouse model of vaginal candidiasis. Furthermore, loss of VPS21 does not synergize with established mechanisms of azole resistance, such as overexpression of efflux pumps or of Erg11p, the target enzyme of the azoles. In summary, although loss of VPS21 function enhances C. albicans survival after azole treatment in vitro, it does not seem to affect azole susceptibility in vivo.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 In Vivo Indicators of Cytoplasmic, Vacuolar, and Extracellular pH Using pHluorin2 in Candida albicans.(Estados Unidos: mSphere, 2017., 2019-09-24) Tournu, Heléne; Luna Tapia, Arturo; Peters, Brian M.; Palmer, Glen E.; American Society for Microbiology.Environmental or chemically induced stresses often trigger physiological responses that regulate intracellular pH. As such, the capacity to detect pH changes in real time and within live cells is of fundamental importance to essentially all aspects of biology. In this respect, pHluorin, a pH-sensitive variant of green fluorescent protein, has provided an invaluable tool to detect such responses. Here, we report the adaptation of pHluorin2 (PHL2), a substantially brighter variant of pHluorin, for use with the human fungal pathogen Candida albicans. As well as a cytoplasmic PHL2 indicator, we describe a version that specifically localizes within the fungal vacuole, an acidified subcellular compartment with important functions in nutrient storage and pH homeostasis. In addition, by means of a glycophosphatidylinositolanchored PHL2-fusion protein, we generated a cell surface pH sensor.