Functional and Comparative Analysis of Centromeres Reveals Clade-Specific Genome Rearrangements in Candida auris and a Chromosome Number Change in Related Species.

Arunaloke Chakrabarti,Michael Lorenz,Aswathy Narayanan,Pavitra Selvakumar,Promit Ganguly,Rajendra Prasad,Rahul Siddharthan,Kaustuv Sanyal,Shivaprakash M. Rudramurthy,Rakesh Netha Vadnala

doi:10.1128/mbio.00905-21

Abstract

ABSTRACTThe thermotolerant multidrug-resistant ascomycete Candida auris rapidly emerged since 2009 causing systemic infections worldwide and simultaneously evolved in different geographical zones. The molecular events that orchestrated this sudden emergence of the killer fungus remain mostly elusive. Here, we identify centromeres in C. auris and related species, using a combined approach of chromatin immunoprecipitation and comparative genomic analyses. We find that C. auris and multiple other species in the Clavispora/Candida clade shared a conserved small regional GC-poor centromere landscape lacking pericentromeres or repeats. Further, a centromere inactivation event led to karyotypic alterations in this species complex. Interspecies genome analysis identified several structural chromosomal changes around centromeres. In addition, centromeres are found to be rapidly evolving loci among the different geographical clades of the same species of C. auris. Finally, we reveal an evolutionary trajectory of the unique karyotype associated with clade 2 that consists of the drug-susceptible isolates of C. auris.

Highlights

IMPORTANCE Candida auris, the killer fungus, emerged as different geographical clades, exhibiting multidrug resistance and high karyotype plasticity
The homolog of CENP-ACse4 was identified in C. auris, using the C. albicans CENP-ACse4 protein sequence as the query against the C. auris genome (GenBank assembly GCA_002759435.2 of the clade 1 isolate B8441) [30]
High amino acid sequence similarities with other proteins of the CENP-A family and typical localization patterns of the clustered centromeres at the nuclear periphery confirmed that the identified protein is, CENP-ACse4 in C. auris

Summary

Introduction

IMPORTANCE Candida auris, the killer fungus, emerged as different geographical clades, exhibiting multidrug resistance and high karyotype plasticity. First isolated from an infected ear of a patient in Japan in 2009, Candida auris emerged as a multidrug-resistant opportunistic fungal pathogen causing nosocomial infections worldwide in a short time span [1,2,3,4,5]. It can survive at elevated temperatures and high salt concentrations, which otherwise act as physiological barriers to. Functional and comparative analysis of centromeres reveals clade-specific genome rearrangements in Candida auris and a chromosome number change in related species. Centromeres with homologous DNA sequences often participate in chromosomal rearrangements that result in chromosomal shuffling which can drive karyotype evolution and chromosome number alterations, contributing to the emergence of a new species [16, 17, 29]

Methods

Results

Conclusion