Glucan-Associated Protein Modulations and Ultrastructural Changes of the Cell Wall inCandida albicansTreated with Micafungin, a Water-Soluble, Lipopeptide Antimycotic

Abstract

The composition of glucan-associated proteins (GAP) in the cell wall of Candida albicans was strongly affected by treatment with a sub-MIC yet beta-glucan synthesis inhibitory concentration (0.01 microg/ml) of FK463 (micafungin). Namely, a decrease in enzymes of glucose metabolism (mostly enolase and a novel 40 kDaltons component, here identified as the enzyme fructose-1,6-biphosphate aldolase) was observed, and this was coupled with an increase in two beta1-3 exo-glucanase isoforms (34 and 44 kDa, respectively). No GAP changes were detected in the same strain of the fungus made resistant to the drug, attesting to the specificity of the observed cell wall protein modulation. In addition, GAP changes were accompanied by marked ultrastructural alterations upon treatment with the sub-MIC dose of the drug, the majority of which was an aberrant cell surface morphology and a derangement of the normal layering of the cell wall. Our data demonstrate that sub-MIC doses of micafungin do critically affect not only the beta-glucan synthetic machinery but also protein composition and the whole cell wall structure of Candida albicans.

Anidulafungin Is Fungicidal and Exerts a Variety of Postantifungal Effects against Candida albicans , C. glabrata , C. parapsilosis , and C. krusei isolates

“…The cell wall defects of Candida cells recovered during PAFE experiments were profound and long-lasting, as demonstrated by electron micrographs of isolates of all four species tested. The electron micrographs are consistent with descriptions of aberrant cell surface morphology and derangements of the normal layering of the cell wall in C. albicans cells exposed to micafungin (1). Interestingly, the cell wall changes were evident in our study even though the isolates were cultured for 24 h on SDA prior to electron microscopy.…”

Caspofungin‐Mediated β‐Glucan Unmasking and Enhancement of Human Polymorphonuclear Neutrophil Activity againstAspergillusand Non‐AspergillusHyphae

“…This action upsets the equilibrium required to maintain cell wall architecture, ultimately causing increased ␤-glucan exposure [15,24]. In our experiments, exposure of Aspergillus species, Fusarium species, and S. apiospermum to a subinhibitory concentration of caspofungin (0.0625 g/mL) resulted in a marked increase in ␤-glucan exposure that was associated with a significant increase in PMN-mediated hyphal damage.…”

Increase of Virulence and Its Phenotypic Traits in Drug-Resistant Strains of Candida albicans

“…The resistance phenotype was stable after multiple (50) passages in culture. Strains CO23 S , CO23 RFLC , and CO23 RFK had identical electrophoretic karyotypes, as determined by pulse-field gel electrophoresis, performed as reported in previous studies (1).…”

“…Thus, we investigated whether acquisition of resistance to FLC or FK was reflected by measurable effects on pathogenicity of the fungus. For this purpose, we generated two strains resistant to FLC or FK (strain CO23 RFLC or CO23 RFK , respectively) from a vaginal clinical isolate of C. albicans (CO23 S ) which was fully susceptible to azoles and echinocandins (1). These three strains were compared for expression levels and/or mutations of drug resistance-related genes and for morphological and ultrastructural characteristics, including putative virulence traits in vitro and in vivo.…”