bioRxiv Science⌕ Search

bioRxiv · 10.1101/2023.10.20.563341

Genomic epidemiology and antifungal-resistant characterization of Candida auris, Colombia, 2016-2021

Abstract

Since 2016 in Colombia, ongoing transmission of Candida auris has been reported in multiple cities. Here, we provide an updated description of C. auris genomic epidemiology and the dynamics of antifungal resistance in Colombia. We sequenced 99 isolates from C. auris cases with collection dates ranging from June 2016 to January 2021; the resulting sequences coupled with 103 previously generated sequences from C. auris cases were described in a phylogenetic analysis. All C. auris cases were of clade IV. Of the 182 isolates with antifungal susceptibility data, 67 (37%) were resistant to fluconazole, and 39 (21%) were resistant to amphotericin B. Isolates predominately clustered by country except for 16 isolates from Bogota, Colombia, which grouped with isolates from Venezuela. The largest cluster (N=166 isolates) contained two subgroups. The first subgroup contained 26 isolates, mainly from Cesar; of these 85% (N=22) were resistant to fluconazole. The second subgroup consisted of 47 isolates from the north coast; of these, 81% (N=38) were resistant to amphotericin B. Mutations in the ERG11 and TAC1B genes were identified in fluconazole-resistant isolates, and two amino acid substitutions in PSK76257-(FLO8) and PSK74852 genes were associated with higher minimum inhibitory concentration values for amphotericin B. This work may help identify mechanisms conferring azole and amphotericin B resistance in C. auris. Overall, C. auris cases from different geographic locations in Colombia exhibited high genetic relatedness, suggesting continued transmission between cities since 2016. These findings also suggest a lack of or minimal introductions of different clades of C. auris into Colombia. IMPORTANCECandida auris is an emerging fungus that presents a serious global health threat and has caused multiple outbreaks in Colombia. This work discusses the likelihood of introductions and local transmission of C. auris and provides an updated description of the molecular mechanisms associated with antifungal resistance in Colombia. Efforts like this tracking genomic variation provide information about the evolving C. auris burden that could help guide public health strategies to control C. auris spread.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Misas, E., Escandon, P., Gade, L., Caceres, D. H., Hurst, S., Le, N., Min, B., Lyman, M., Duarte, C., Chow, N. A.. 2023-10-24. Genomic epidemiology and antifungal-resistant characterization of Candida auris, Colombia, 2016-2021. https://doi.org/10.1101/2023.10.20.563341

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Genomic correlates of metastatic competence and progression in human melanoma

Genomic events and their timing that grant a primary tumour the competence to disseminate remain poorly defined. We performed sequencing of 247 stage I/II primary cutaneous melanomas (CMs) and 60 matched metastases without intervening therapy from a prospectively followed registry cohort with a median followup of 92 months, integrating copy-number, mutational, protein and spatial-transcriptomic analyses. Relapse was not distinguished by oncogenic point mutations, which were largely shared between primaries and metastases, but by somatic copy-number alterations (SCNAs) and global chromosomal instability. We defined OncoCycle, a six-gene copy-number signature (amplification of CDK4, MCL1 and CD276; biallelic loss of CDKN2A, CDKN2B and TP53BP1) that predicted relapse independently of established clinicopathological features in melanoma, and a pan-cancer analysis. In matched pairs, metastatic progression was driven by continued copy-number evolution and reduction in intra-tumoural heterogeneity, rather than by acquired point mutations, and OncoCycle alterations from primary tumours were preserved in metastasis seeding clones. Clonal reconstruction revealed both monoclonal and polyclonal metastasis seeding, and spatial transcriptomics resolved copy-number-defined metastatic subclones occupying and programming distinct immune and stromal niches. Thus, metastatic competence was primed early by focal SCNAs on a background of chromosomal instability, elaborated by continued copy-number evolution during dissemination and spatio-temporal interactions with the tumour-microenvironment.

genomics↗

Identifying, phasing, and structurally annotating sex chromosomes for genome assemblies using CBS-tools

A complete reference genome for species with chromosomally-determined separate sexes should contain scaffolds for all sex chromosome homologs. However, sex chromosomes present distinct computational challenges compared to autosomes. Here we present a k-mer based analysis that utilizes whole-genome sequencing of a few sex-identified isolates: Cytogenetics-By-Sequencing (CBS) tools. Unlike other approaches that typically address one aspect of the sex chromosomes, CBS-tools strives to guide users from the discovery of the heterogametic sex through identifying the sex-determination region (SDR). The core of CBS-tools is automated quantification of sex-specific k-mers in order to predict the heterogametic sex. Using publicly-available datasets, CBS-tools correctly identified the known sex-system of the 31 species tested. Additionally, we used these k-mers to verify and correct phasing of sex chromosomes between haplotypes in species representing different sex-systems. Finally, we used these k-mers to delimit the SDR boundary using an interactive web platform. CBS-tools was developed with previously unexplored sex chromosome systems in mind, but is also suitable for well-examined sex chromosome pairs.

genomics↗

Evolutionary dynamics of the insertion sequence IS6110 in the Mycobacterium tuberculosis complex

Insertion sequences (IS) are the most common type of transposable element in prokaryotes and shape the structure of genomes through transposition and by providing a substrate for recombination. Despite the mutational impact of IS, the evolutionary dynamics of most elements in host species remain unknown. Here we study the dynamics of IS6110 in 10,000 strains of the Mycobacterium tuberculosis complex (MTBC). We developed a tool that allows the detection and comparison of IS insertions from short reads without using a reference genome. Using ancestral state reconstruction (ASR) on presence-absence patterns of IS6110, we describe the distribution of copy numbers (CNs) in the MTBC, infer birth rates of the element, and identify genomic regions with large numbers of parallel IS6110 insertions. Copy numbers in the MTBC range from 1 in some clades to more than 30 in strains of La3 (M. orygis). IS6110 birth rates scale approximately linearly with copy number and are elevated on terminal branches, consistent with the delayed action of purifying selection. A key characteristic of IS6110 is its occurrence in hotspots: the 5% most frequently targeted regions account for half of all independent insertion events. The motif 5'-TCTCAAAW-3' is enriched around target sites and in hotspots, suggesting that the accumulation of insertions in these regions results through a combination of non-random insertion and purifying selection in other regions. To conclude the study, we propose a niche constraints model according to which the distribution of IS6110 in the MTBC is governed by the rarity of regions that have both suitable DNA properties and little functional value for the host.

genomics↗