Further studies on the intracellular behavior of Torulopsis glabrata

Abstract

The growth of Torulopsis glabrata was inhibited in glucose-peptone broth containing 10 to 20% normal human serum. Addition of iron to the medium diminshed the fungistatic effect. The intracellular growth of T. glabrata was remarkably restricted within mouse macrophages maintained in vitro, but this growth restriction was not caused by the limitation of iron imposed by the serum in the medium. The intracellular growth of T. glabrata within a very small percentage of the macrophages was not obviously related to the failure of lysosomal fusion to the phagosomes in those cells. The studies did not permit definite conclusions regarding the viability of the inhibited yeasts, but results suggested that a large portion of them survived. Potentially misleading artifacts of the technique for assessment of the intracellular behavior of the fungus were detected and are discussed.

One Small Step for a Yeast - Microevolution within Macrophages Renders Candida glabrata Hypervirulent Due to a Single Point Mutation

“…In previous works, we and others have addressed the ability of C. glabrata to not only resist the conditions inside the macrophage phagosome, but to even persist and thrive inside [16] – [19] . Yet, these investigations have mainly focused on the short-term interaction between host and fungus, lasting for hours up to days.…”

“…In previous experiments, we observed that C. glabrata microcolonies were regularly found in close proximity to mononuclear cells within murine tissues [15] and speculated that C. glabrata may face constant exposure to these phagocytes during infection. In fact, we and others have shown that C. glabrata can survive and replicate inside macrophages for days in vitro [16] – [19] . During commensal growth, fungi are repeatedly exposed, at least transiently, to host-induced stresses (e.g.…”

“…Although C. glabrata can reside and replicate inside the macrophage phagosome [36] , this hostile environment likely represents a substantial selective pressure. The short-term survival strategies of C. glabrata inside macrophages have been addressed in previous investigations [16] , [18] , [19] . However, longer-term interactions likely pose different challenges to the fungus.…”

Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate

“…Lactate-grown cells were taken up by macrophages less efficiently, but they were more efficient at killing and escaping phagocytosis ( Ene et al, 2013 ). Of note, C. glabrata cells also resist killing by macrophages and have evolved distinct strategies for intracellular survival ( Otto and Howard, 1976 ; Kaur et al, 2007 ; Seider et al, 2010 ). However, in these studies C. glabrata cells were grown in glucose.…”

Rilopirox ‐ a New Hydroxypyridone Antifungal with Fungicidal Properties

“…3). Owing to its low susceptibility to a number of antimycotics, this organism is of increasing interest as a target f?r new antifungals (9,10). As with Ciclopirox which acts partly by complexing tnetal ions, the efficacy of rilopirox depends on the free metal ion concentration of the growth medium used.…”