Genomic rearrangements uncovered by genome-wide co-evolution analysis of a major nosocomial pathogenEnterococcus faecium
Authors: Top Janetta , Arredondo-Alonso Sergio , Schürch Anita C. , Puranen Santeri , Pesonen Maiju , Pensar Johan , Willems Rob J.L. , Corander Jukka 
Published: October 2020

AbstractEnterococcus faeciumis a gut commensal of the gastro-digestive tract, but also known as nosocomial pathogen among hospitalized patients. Population genetics based on whole-genome sequencing has revealed thatE. faeciumstrains from hospitalized patients form a distinct clade, designated as clade A1 and that plasmids are major contributors to the emergence of nosocomialE. faecium. Here we further explored the adaptive evolution ofE. faeciumusing a genome-wide co-evolution study (GWES) to identify co-evolving SNPs. We identified three genomic regions harboring large numbers of SNPs in tight linkage which are not proximal to each other based on the completely assembled chromosome of clade A1 reference hospital isolate AUS0004. Close examination of these regions revealed that they are located at the borders of four different types of large-scale genomic rearrangements, insertion sites of two different genomic islands and an IS30-like transposon. In non-clade A1 isolates, these regions are adjacent to each other and they lack the insertions of the genomic islands and IS30-like transposon. Additionally, among the clade A1 isolates there is one group of pet isolates lacking the genomic rearrangement and insertion of the genomic islands, suggesting a distinct evolutionary trajectory.In silicoanalysis of the biological functions of the genes encoded in three regions revealed a common link to a stress response. This suggests that these rearrangements may reflect adaptation to the stringent conditions in the hospital environment, such as antibiotics and detergents, to which bacteria are exposed. In conclusion, to our knowledge, this is the first study using GWES to identify genomic rearrangements, suggesting that there is considerable untapped potential to unravel hidden evolutionary signals from population genomic data.Impact statementEnterococcus faeciumhas emerged as an important nosocomial pathogen around the world. Population genetics revealed that clinicalE. faeciumstrains form a distinct clade, designated as clade A1 and that plasmids are major contributors to the emergence of nosocomialE. faecium. Here, the adaptive evolution ofE. faeciumwas further explored using an unsupervised machine learning method (SuperDCA) to identify genome-wide co-evolving SNPs. We identified three genomic regions harboring large numbers of SNPs in tight linkage which are separated by a large chromosomal distance in a clinical clade A1 reference isolate, but appeared adjacent to each other in non-clade A1 isolates. We identified four different types of large-scale genomic rearrangements and in all cases, we found insertion of two different genomic islands and an insertion element at the border. In contrast, no genomic rearrangement and insertions were identified among a group of clade A1 pet isolates, suggesting a distinct evolutionary trajectory. Based on thein silicopredicted biological functions, we found a common link to a stress response for the genes encoded in three regions. This suggests that these rearrangements may reflect adaptation to the stringent conditions in the hospital environment, such as antibiotics and detergents, to which bacteria are exposed.Data summaryRaw core-genome alignment (1.1 MB, Harvest suite v1.1.2), including the 1,644 Clade A isolates and the completeE. faeciumAUS0004 (accession numberCP003351) as a reference is available under the following gitlab repositoryhttps://gitlab.com/sirarredondo/efm_gwes.