MSH2 Gene Point Mutations Are Not Antifungal Resistance Markers in Candida glabrata
Autor/es
Bordallo-Cardona, María Ángeles; Agnelli, Caroline; Gómez-Nuñez, Ana; Sánchez-Carrillo, Carlos; Bouza, Emilio; [et al.]Fecha
2018-12-21Tipo de documento
articleÁrea/s de conocimiento
Ciencias BiomédicasResumen
The high rates of antifungal resistance in Candida glabrata may be facilitated
by the presence of alterations in the MSH2 gene. We aimed to study the sequence
of the MSH2 gene in 124 invasive C. glabrata isolates causing incident
episodes of candidemia (n 81), subsequent candidemia episodes (n 9), endocarditis
(n 2), and in vitro-generated echinocandin-resistant isolates (n 32) and assessed
its relationship with genotypes, acquisition of antifungal resistance in vivo
and in vitro, and patient prognosis. The MSH2 gene was sequenced, and isolates
were genotyped using six microsatellite markers and multilocus sequence typing
(MLST) based on six housekeeping genes. According to EUCAST, isolates causing
candidemia (n 90) were echinocandin susceptible, and four of them were fluconazole
resistant (MIC 64 mg/liter). One isolate obtained from a heart valve was resistant
to micafungin and anidulafungin (MICs, 2 mg/liter and 1 mg/liter, respectively).
MSH2 gene mutations were present in 44.4% of the incident isolates, the most common
being V239L. The presence of MSH2 mutations was not correlated with in vitro
or in vivo antifungal resistance. Microsatellite and MLST revealed 27 genotypes and
17 sequence types, respectively. Fluconazole-resistant isolates were unrelated. Most
MSH2 mutations were found in cluster isolates; conversely, some mutations were
found in more than one genotype. No clinical differences, including previous antifungal
use, were found between patients infected by wild-type MSH2 gene isolates
and isolates with any point mutation. The presence of MSH2 gene mutations in C.
glabrata isolates causing candidemia is not correlated with specific genotypes, the
promotion of antifungal resistance, or the clinical outcome.