Clonal Population of Flucytosine-ResistantCandida tropicalisfrom Blood Cultures, Paris, France

Abstract

Candida tropicalis is a diploid ascomycetes yeast responsible for 4%-24% of candidemia. Resistance to fl ucytosine is rarely described for this species but was observed for 45 (35%) of 130 C. tropicalis isolates recovered from blood cultures in the Paris area in a 4-year survey. The aims of this study were to test the hypothesis that the fl ucytosine-resistant isolates could represent a subgroup and to determine the relationship between epidemiologic and genomic data. Epidemiologic data and gene sequences were analyzed, and molecular typing was performed. Our results suggest that a clone of fl ucytosine-resistant isolates, associated with malignancies and a lower mortality than that for other C. tropicalis isolates, is widespread in the Paris area. We propose the analysis of 2 polymorphic microsatellite markers coupled with URA3 sequencing to track the clone. C andida tropicalis is a diploid ascomycetes yeast commonly found on the skin and in digestive tracts of healthy human hosts worldwide (1). Infections caused by C. tropicalis are reported in 4%-24% of patients with candidemia, depending on the country of study, underlying risk factors, and period of study (2). Primary resistance to fl ucytosine (5FC) occurs in <5% of all Candida species except for C. krusei, in which it is detected in up to 28% of isolates (3). It was thus unexpected to observe 35% resistance to 5FC among C. tropicalis isolates recovered from blood cultures in the active surveillance program on yeast-related fungemia implemented by the French National Reference Center for Mycoses and Antifungals (NRCMA) in the Paris area. The YEASTS program is designed to analyze the epidemiologic trends of yeast fungemia by collecting isolates and epidemiologic and clinical data. The second objective is to study the clinical isolates in terms of species, antifungal susceptibility profi les, and genetic diversity to look for associations between subtypes of isolates and epidemiologic/clinical parameters. To test the hypothesis that the 5FC resistant ( R 5FC) isolates could represent a different species or a subgroup, the R 5FC and susceptible ( S 5FC)

A Novel Flucytosine-Resistant Yeast Species, Candida pseudoaaseri, Causes Disease in a Cancer Patient

“…For other clinically important yeasts, e.g., C. albicans and C. tropicalis, resistances to flucytosine were also described in the literature (17,21). These resistances are determined not only genetically; they also cause differences in phenotypical and epidemiological characteristics of susceptible and nonsusceptible yeast populations, respectively.…”

“…These resistances are determined not only genetically; they also cause differences in phenotypical and epidemiological characteristics of susceptible and nonsusceptible yeast populations, respectively. Desnos-Ollivier et al (17) have shown that a flucytosinenonsusceptible C. tropicalis subgroup isolated from blood cultures has a higher incidence in patients with malignancies and is associated with lower mortality related to the infection. Currently, flucytosine has only a marginal therapeutic impact; however, the identification of the resistance is important for differentiation of Candida species, as demonstrated in this study.…”

Prior Caspofungin Exposure in Patients with Hematological Malignancies Is a Risk Factor for Subsequent Fungemia Due to Decreased Susceptibility in Candida spp.: a Case-Control Study in Paris, France

“…A matched case-control study was nested within the YEASTS program, an active surveillance program on yeast BSI implemented in the Paris area in France (5). The study population included patients Ͼ17 years of age suffering from hematological diseases and Candida BSI between 1 October 2002 and 1 February 2010.…”

Loss of Heterozygosity of FCY2 Leading to the Development of Flucytosine Resistance in Candida tropicalis

“…FCY2, encoding a purine-cytosine permease, is involved in the uptake of 5FC, and URA3, encoding an orotidine 5Ј-phosphate decarboxylase, is involved in the metabolic pathway of uridylmonophosphate (UMP) in nucleic acid synthesis. Mutations on FCY1, FCY2, FUR1, or URA3 can result in 5FC resistance in certain yeast species (5,14,16,18,23,27,33). Interestingly, 5FC-resistant clinical isolates have been reported to be genetically related (6,14).…”