Genomic Analyses of a Fungemia Outbreak Caused by Lodderomyces elongisporus in a Neonatal Intensive Care Unit in Delhi, India.

Abstract

Lodderomyces elongisporus is a recently emerging yeast pathogen predominantly reported in adult patients who had immunosuppression and/or intravenous access devices. Here, we report a fungemia outbreak caused by L. elongisporus in a neonatal intensive care unit (NICU) in Delhi, India, from September 2021 to February 2022. All 10 neonates had low birthweight, and nine of the patients survived after amphotericin B treatment. Whole-genome sequence analyses of the patient isolates as well as those from other sources in India grouped them into two clusters: one cluster consists of isolates exclusively from stored apples and the other cluster includes isolates from patients, clinical environments, and stored apples. All outbreak strains from patients were closely related to each other and showed highly similar heterozygosity patterns across all 11 major scaffolds. While overall very similar, strains from the inanimate environment of the same neonatal intensive care unit showed loss of heterozygosity at scaffold 2 (NW_001813676) compared to the patient strains. Interestingly, evidence for recombination was found in all samples. All clinical strains were susceptible to 10 tested antifungal drugs, and comparisons with strains with high fluconazole MICs derived from the surface of stored apples revealed significant genome divergence between the clinical and apple surface strains, including 119 nonsynonymous single nucleotide polymorphisms (SNPs) in 24 triazole resistance-related genes previously found in other Candida spp. Together, our results indicate significant diversity, recombination, and persistence in the hospital setting and a high rate of evolution in this emerging yeast pathogen. IMPORTANCE Lodderomyces elongisporus was initially considered a teleomorph of Candida parapsilosis. However, DNA sequence analyses revealed it as a distinctive species. Invasive infections due to L. elongisporus have been reported globally. We report an outbreak of fungemia due to L. elongisporus in a NICU affecting 10 preterm, low-birthweight neonates during a period of 6 months. The outbreak investigation identified two environmental sites, the railing and the temperature panel of the neonate open care warmer, harboring L. elongisporus. Whole-genome sequencing confirmed that the neonate isolates were closely related to each other whereas strains from the inanimate clinical environment were related to clinical strains but showed a marked loss of heterozygosity. Further, L. elongisporus strains recovered previously from the surface of stored apples showed high fluconazole MICs and alterations in triazole resistance-related genes. Genome-wide SNP comparisons revealed recombination as an important source for genomic diversity during adaptation of L. elongisporus to different environments.