Sterol compositions and susceptibilities to amphotericin B of environmental Cryptococcus neoformans isolates are changed by murine passage

Abstract

Previous studies have shown that sequential isolates from patients with persistent Cryptococcus neoformans meningoencephalitis can vary in sterol composition and susceptibility to antifungal drugs. To investigate the potential of host factors as mediators of this phenomenon, we compared fungal susceptibilities of environmental and clinical isolates from a limited geographic area. Clinical isolates were less susceptible to amphotericin B than environmental isolates. Five environmental isolates were passaged through BALB/c murine hosts; the passaged isolates had changes in sterol composition and reduced amphotericin B susceptibilities relative to those of the parent isolates. In contrast, murine passage of these isolates did not alter their susceptibilities to fluconazole. The results confirm that changes in sterol composition and antifungal susceptibility can occur in vivo as a result of host factors and suggest that human infection can result in selection of variants with reduced susceptibilities to amphotericin B.

Amphotericin B resistance of Aspergillus terreus in a murine model of disseminated aspergillosis

“…Nevertheless, amphotericin B resistance has also been reported in C. albicans [31], Cr. neoformans [32,33] and Ustilago maydis [34] without signi®cant alterations in sterol biosynthesis. In these cases, the underlying mechanism of such resistance remains unclear.…”

Increased release of glucuronoxylomannan antigen and induced phenotypic changes in Trichosporon asahii by repeated passage in mice

“…neoformans also changes its phenotype including colony type, capsule size, melanin production, GXM structure, virulence for mice, sterol composition and antifungal susceptibility after passages in vitro and in vivo [11,12,14,15]. Furthermore, serial Crypt.…”

“…This process is thought to allow some fungi to escape eradication by the host immune system [11,[13][14][15]. However, to our knowledge, there are no studies that have previously examined phenotypic changes within the genus Trichosporon after passages in vivo.…”

“…neoformans change their phenotypes when they are subcultured repeatedly or passaged in vivo [11][12][13][14][15][16]. C. albicans spontaneously switches the morphology of its colonies into at least seven general phenotypes [16].…”

“…In this regard, clinically important fungi such as Candida albicans and Cryptococcus neoformans are known to change their phenotype after repeated subcultures or in-vivo passages [11][12][13][14][15][16]. This process is thought to allow some fungi to escape eradication by the host immune system [11,[13][14][15].…”