Abstract
BackgroundCandida parapsilosis is a common cause of invasive candidiasis, especially in newborn infants, and infections have been increasing over the past two decades. C. parapsilosis has been primarily studied in pure culture, leaving gaps in understanding of its function in a microbiome context.ResultsHere, we compare five unique C. parapsilosis genomes assembled from premature infant fecal samples, three of which are newly reconstructed, and analyze their genome structure, population diversity, and in situ activity relative to reference strains in pure culture. All five genomes contain hotspots of single nucleotide variants, some of which are shared by strains from multiple hospitals. A subset of environmental and hospital-derived genomes share variants within these hotspots suggesting derivation of that region from a common ancestor. Four of the newly reconstructed C. parapsilosis genomes have 4 to 16 copies of the gene RTA3, which encodes a lipid translocase and is implicated in antifungal resistance, potentially indicating adaptation to hospital antifungal use. Time course metatranscriptomics and metaproteomics on fecal samples from a premature infant with a C. parapsilosis blood infection revealed highly variable in situ expression patterns that are distinct from those of similar strains in pure cultures. For example, biofilm formation genes were relatively less expressed in situ, whereas genes linked to oxygen utilization were more highly expressed, indicative of growth in a relatively aerobic environment. In gut microbiome samples, C. parapsilosis co-existed with Enterococcus faecalis that shifted in relative abundance over time, accompanied by changes in bacterial and fungal gene expression and proteome composition.ConclusionsThe results reveal potentially medically relevant differences in Candida function in gut vs. laboratory environments, and constrain evolutionary processes that could contribute to hospital strain persistence and transfer into premature infant microbiomes.FVTWG-mFNui5xgWwFcfPTvVideo abstract
Highlights
Candida parapsilosis is a common cause of invasive candidiasis, especially in newborn infants, and infections have been increasing over the past two decades
Recovery of novel Candida strain genomes A large dataset of a mixture of previously analyzed and newly generated infant gut and neonatal intensive care units (NICUs) shotgun metagenome samples were analyzed for the purpose of reconstructing novel Candida genomes
Unique Candida genomes were assembled for this study (Table 1), five C. albicans genomes, and three C. parapsilosis genomes
Summary
Candida parapsilosis is a common cause of invasive candidiasis, especially in newborn infants, and infections have been increasing over the past two decades. A variety of Candida species cause candidiasis and are recognized as a serious public health challenge, especially among immunocompromised and hospitalized patients [3, 4]. Candida albicans most commonly has been recognized as the cause of candidiasis, and as a result, is the focus of the majority of Candida research [4,5,6]. Candida parapsilosis, despite being considered less virulent than C. albicans, is the Candida species with the largest increase in incidence since 1990 [6]. Understanding behavior of C. parapsilosis, both as a commensal organism and opportunistic pathogen, is incredibly important
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