Sequencing of FKS Hot Spot 1 from Saprochaete capitata To Search for a Relationship to Reduced Echinocandin Susceptibility

Abstract

, formerly known as , is an emerging fungal pathogen with low susceptibility to echinocandins. Here, we report the nucleotide sequence of the hot spot 1 region of the gene ( HS1), which codifies for the catalytic subunit of β-1,3-d-glucan synthase, the target of echinocandins. For that purpose, we first designed degenerated oligonucleotide primers derived from conserved flanking regions of the HS1 segment of 12 different fungal species. Interestingly, analysis of the translated HS1 sequences of 12 isolates of revealed that all of them exhibited the same F-to-L substitution in a position that is highly related to reduced echinocandin susceptibility.

Bloodstream Infections Caused by Magnusiomyces capitatus and Magnusiomyces clavatus : Epidemiological, Clinical, and Microbiological Features of Two Emerging Yeast Species

“…S1). MICs of azoles were comparable to data from previous studies ( 6 , 8 , 9 , 28 , 29 ), and MICs of anidulafungin and caspofungin were high, as anticipated ( 9 , 30 ). In contrast, MICs of micafungin were lower, with M. clavatus isolates having significantly lower MICs (MIC 50 , 0.5 mg/L) compared to M. capitatus (MIC 50 , 2 mg/L; P < 0.001).…”

Management of Invasive Infections due to a Rare Arthroconidial Yeast, Saprochaete capitata, in Two Patients with Acute Hematological Malignancies

“…In our observation, triazoles (except for fluconazole) showed potent in vitro activity against Saprochaete capitata with low MIC values. This is in agreement with data reported in the literature, which found that itraconazole, voriconazole and posaconazole (MIC ranges, 0.12 to 0.5, 0.25 to 0.5, and 0.03 to 0.5 µg/mL, respectively) have low MICs against Saprochaete capitata, but not fluconazole [17,36,46].…”

“…Clinical breakpoints for Saprochaete capitata are not available; however, antifungal susceptibility assays are recommended on all isolates [45]. Saprochaete capitata is considered intrinsically resistant to echinocandins; in particular, it was recently found that an F-to-L amino acid substitution in a highly conserved position of the catalytic subunit of β-1,3-dglucan synthase, Fks1p, might be related to a reduced susceptibility to echinocandins [46].…”

Invasive Saprochaete Infections: An Emerging Threat to Immunocompromised Patients

“…Based on in vitro susceptibility results from numerous case reports and case series, these organisms appear to be intrinsically resistant to echinocandins and highly resistant to fluconazole [3,11]. A mutation in the FKS gene hot spot 1 (FKS HS1) which codes a subunit in the β-1,3-D -glucan synthase was detected at a position highly associated with echinocandin resistance in S. capitata isolates [68]. Prolonged treatment with echinocandins (particularly caspofungin) appears to be a risk factor for breakthrough infections with these organisms [32,68], although breakthrough IFIs while on fluconazole, posaconazole and amphotericin B have also been reported [17,38,45,48,49,52].…”

“…A mutation in the FKS gene hot spot 1 (FKS HS1) which codes a subunit in the β-1,3-D -glucan synthase was detected at a position highly associated with echinocandin resistance in S. capitata isolates [68]. Prolonged treatment with echinocandins (particularly caspofungin) appears to be a risk factor for breakthrough infections with these organisms [32,68], although breakthrough IFIs while on fluconazole, posaconazole and amphotericin B have also been reported [17,38,45,48,49,52]. Minimum inhibitory concentration (MIC) values for voriconazole (0.03-1 mg/L), amphotericin B (0.03-2 mg/L), itraconazole (0.01-1 mg/L) and posaconazole (0.03-1 mg/L) are generally low for both fungi [7,11,29,34,36,44,45,47].…”