Comparative Genomics of an Emerging Multidrug-Resistant <i>bla</i>_NDM-Carrying ST182 Lineage in <i>Enterobacter cloacae</i> Complex

• Main Authors: Angeliki Mavroidi (Author), Elisavet Froukala (Author), Athanasios Tsakris (Author)
• Format: Book
• Published: MDPI AG, 2024-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antibiotics13060535; 2079-6382
• Keywords: <i>Enterobacter cloacae</i> complex; <i>E. hormaechei</i>; NDM carbapenemase; MLST; WGS; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 13, Iss 6, p 535 (2024)

Background: <i>Enterobacter cloacae</i>, <i>E. hormaechei</i> and related subspecies remain the most clinically relevant among the <i>Enterobacter cloacae</i> complex (ECC). Carbapenemase-producing ECC strains are increasingly identified in hospital-acquired infections and usually belong to four main multilocus sequence types (MLST STs) named ST114, ST93, ST90 and ST78. Instead, ST182 has been sporadically reported among <i>E. hormaechei</i> strains, and recently, outbreaks of <i>bla</i>_NDM-producing ST182 clonal strains have emerged. Herein, we aimed to investigate the presence of ST182 and explore its evolution and modes of <i>bla</i>_NDM acquisition. Methods: A phylogenetic analysis of 646 MLST STs identified among 4685 <i>E. hormaechei</i> whole-genome sequencing (WGS) assemblies deposited in public repositories was performed, as well as an in silico comparative and phylogenomic analyses for 55 WGS assemblies of ST182. <i>bla</i>_NDM-harboring contigs were also compared to published plasmid sequences. Results: ST182 <i>E. hormaechei</i> strains were recovered from patients on five continents during 2011-2021. They were divided into three major genomic clusters, comprising a separate clonal complex with six other STs. In 30 out of 55 ST182 WGS assemblies, <i>bla</i>_NDM-harboring structures were identified that were similar to the plasmids predominant in Gram-negative bacteria, harboring resistance genes to multiple antibiotic classes and virulence genes. No associations between the genomic clusters and the country/continent of isolation or the presence and the plasmid types of the <i>bla</i>_NDM-harboring contigs were observed. Conclusions: Our findings show that ST182 <i>E. hormaechei</i> strains have been identified in the past decade worldwide; 54.5% of them carried diverse <i>bla</i>_NDM genetic structures, suggesting recent acquisition of the <i>bla</i>_NDM alleles. Thus, <i>bla</i>_NDM-harboring ST182 is an emerging multidrug-resistant and virulent lineage in ECC strains that requires close monitoring.