Pan-genome analysis of the Enterobacter hormaechei complex highlights its genomic flexibility and pertinence as a multidrug resistant pathogen

Abstract

BACKGROUND : Enterobacter hormaechei is of increasing concern as both an opportunistic and nosocomial pathogen, exacerbated by its evolving multidrug resistance. However, its taxonomy remains contentious, and little is known about its pathogenesis and the broader context of its resistome. In this study, a comprehensive comparative genomic analysis was undertaken to address these issues. RESULTS : Phylogenomic analysis revealed that E. hormaechei represents a complex, comprising three predicted species, E. hormaechei, E. hoffmannii and E. xiangfangensis, with the latter putatively comprising three distinct subspecies, namely oharae, steigerwaltii and xiangfangensis. The species and subspecies all display open and distinct pan-genomes, with diversification driven by an array of mobile genetic elements including numerous plasmid replicons and prophages, integrative conjugative elements (ICE) and transposable elements. These elements have given rise to a broad, relatively conserved set of pathogenicity determinants, but also a variable set of secretion systems. The E. hormaechei complex displays a highly mutable resistome, with most taxa being multidrug resistant. CONCLUSIONS : This study addressed key issues pertaining to the taxonomy of the E. hormaechei complex, which may contribute towards more accurate identification of strains belonging to this species complex in the clinical setting. The pathogenicity determinants identified in this study could serve as a basis for a deeper understanding of E. hormaechei complex pathogenesis and virulence. The extensive nature of multidrug resistance among E. hormaechei complex strains highlights the need for responsible antibiotic stewardship to ensure effective treatment of these emerging pathogens.