Genomic reconstruction of an azole-resistantCandida parapsilosisoutbreak and the creation of a multilocus sequence typing scheme: a retrospective observational and genomic epidemiology study

• DOI: 10.1101/2024.02.22.24302918
• Publication Date: 2024-07-15T21:45:16Z
• Authors: Phillip Brassington; Frank-Rainer Klef...; Barbara Graf; Roland Pfüller; Oliver Kurzai; Grit Walther; Amelia E. Barber
• Keywords: Candida parapsilosis; Multilocus sequence typing; Molecular Epidemiology

Summary Background Fluconazole-resistant Candida parapsilosis has emerged as a significant healthcare-associated pathogen with propensity to spread patient-to-patient and cause nosocomial outbreaks, similar auris . This study investigates prolonged outbreak of fluconazole-resistant C. across multiple years healthcare centers in Berlin, Germany. Methods In this retrospective observational study, we used whole-genome sequencing isolates from the Berlin other regions within Germany compared them global distribution understand molecular epidemiology outbreak. Additionally, genomic dataset samples identify loci high discriminatory power establish multi-locus sequence typing (MLST) strategy for Findings A clonal, azole-resistant strain was observed causing 33 cases invasive infection 2018-2022 hospitals city. Whole genome revealed that strains were separated by an average 36 single nucleotide variants, while differed outgroup 2,112 variants. Temporal reconstruction indicated transfer patients between facilities likely responsible persistent reimportation drug-resistant clone subsequent person-to-person transmission. German closely related Canada others isolated Middle East Asia. Including clone, identified three distinct ERG11 Y132F lineages Germany, marking first description azole-resistance country its endemic status. Using novel MLST strategy, collection 386 categorized into 62 types, all belonging same type. Interpretation underscores emergence drug resistant fungal pathogens can system, but also around globe. highlights importance monitoring globally continuous surveillance rigorous control measures at local scale. Through large-scale epidemiology, our offers high-resolution view how behaved system fits pathogen. We demonstrate utility scheme genetic investigations faster less expensive alternative whole sequencing. Funding Federal Ministry Education Research, Research Foundation, Health context Evidence before searched PubMed Google Scholar database inception Apr 25, 2024, using search terms “Candida parapsilosis”, “outbreak”, “azole resistance”, and/or “fluconazole” Scholar. applied no language or type restrictions. The candidemia undergone dramatic changes recent years. New pathogenic species, such , have emerged, existing species like increased prominence. There been worrying increase resistance among species. Moreover, numerous outbreaks reported worldwide are challenging due their intermittent nature. overwhelming majority previous work microsatellite markers infer relationships strains, obscuring whether they really clonal nature, understanding temporal transmission dynamics these relationship clones. Added value adds evidence utilizing conjunction hospital records analyze occurred medical centers. demonstrates patient transfers result clones, posting challenge control. reveal is continents, highlighting Furthermore, addresses need rapid differentiation settings establishing validating set four Sanger sequence-based typing, which provide highly tool epidemiologic investigations. Implications available causative agent outbreaks. Clinicians should be aware evolving prevalence emphasizing appropriate antifungal stewardship measures. emphasizes challenges caused inter-hospital role robust coordination facilities. While (WGS) becoming more widely available, it still not many cost, limitations bioinformatic expertise, absence standardized methodology data interpretation. establishment valuable assessment samples, aid tracking containment efforts, results rapidly even where WGS available.