215. Candida glabrata (CG) Bloodstream Infections (BSIs) Are Characterized by Genetically Diverse Populations of Strain Variants Recovered from Positive Blood Cultures (BCs)

BACKGROUND: The long-standing paradigm is that almost all BSIs stem from a single, clonal organism (“single-organism” hypothesis). We hypothesized that CG-positive BCs were comprised of genetically diverse strain variants. METHODS: Five to ten CG colonies were isolated from positive BC bottles from ten distinct patients (pts) for a total of 94 clones, which underwent NextGen short-read sequencing (Illumina). Variants were analyzed using SNPeff, and a phylogeny was constructed with Maximum Likelihood method. RESULTS: BCs harbored a diverse population of CG strains that were unique to each pt [Fig. 1]. All strains were genetically distinct, differing by unique SNPs and insertions-deletions (indels) [Fig. 2-3]. SNPs were ~8-fold more common than indels. Individual genomes from the same time point in the same pt exhibited consistent magnitude of variations relative to reference genome; however, variations were unique, pointing to significant genomic variability that could be both intra- and interclonal. The number of variant sites for within-pt pairwise clone comparisons ranged from 1924-8500. There were 124,145 variant sites when all clones are compared. Roughly half of all SNPs were identical in different samples from a given pt; the remainder were present/absent in at least one sample per pt. Long-read WGS revealed strains with structural variants in each pt, including chromosomal recombinations and gene duplications that were not evident by short-read WGS. A genomic phylogeny construction showed that 94 clones spanned 3 distinct clades that were distinct from the reference strain. Finally, comparison of non-synonymous mutations among intra-pt clones showed overwhelming overrepresentation of adhesin and adhesin-like genes, pointing to possible importance in host adaptation. [Image: see text] [Image: see text] [Image: see text] Venn diagram of core genome SNPs of 5 Candida glabrata recovered from blood cultures of patient C. CONCLUSION: Preliminary analyses revealed genetically diverse populations of C. glabrata in BCs of individuals with BSIs. We are studying phenotypic diversity of strain variants, and the clinical implications of genetically diverse Candida BSIs. DISCLOSURES: Cornelius J. Clancy, MD, Merck (Grant/Research Support) Minh-Hong Nguyen, MD, Merck (Grant/Research Support)