Genomic and geographic context for the evolution of high-risk carbapenem-resistant enterobacter cloacae complex clones ST171 and ST78

Angela Gomez-Simmonds, Medini K. Annavajhala, Zheng Wang, Nenad Macesic, Yue Hu, Marla J. Giddins, Aidan O’Malley, Nora C. Toussaint, Susan Whittier, Victor J. Torres, Anne Catrin Uhlemann

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23 Citations (Scopus)


Recent reports have established the escalating threat of carbapenem-resistant Enterobacter cloacae complex (CREC). Here, we demonstrate that CREC has evolved as a highly antibiotic-resistant rather than highly virulent nosocomial pathogen. Applying genomics and Bayesian phylogenetic analyses to a 7-year collection of CREC isolates from a northern Manhattan hospital system and to a large set of publicly available, geographically diverse genomes, we demonstrate clonal spread of a single clone, ST171. We estimate that two major clades of epidemic ST171 diverged prior to 1962, subsequently spreading in parallel from the Northeastern to the MidAtlantic and Midwestern United States and demonstrating links to international sites. Acquisition of carbapenem and fluoroquinolone resistance determinants by both clades preceded widespread use of these drugs in the mid-1980s, suggesting that antibiotic pressure contributed substantially to its spread. Despite a unique mobile repertoire, ST171 isolates showed decreased virulence in vitro. While a second clone, ST78, substantially contributed to the emergence of CREC, it encompasses diverse carbapenemase-harboring plasmids, including a potentially hypertransmissible IncN plasmid, also present in other sequence types. Rather than heightened virulence, CREC demonstrates lineage-specific, multifactorial adaptations to nosocomial environments coupled with a unique potential to acquire and disseminate carbapenem resistance genes. These findings indicate a need for robust surveillance efforts that are attentive to the potential for local and international spread of high-risk CREC clones.

Original languageEnglish
Article numbere00542-18
Number of pages15
Issue number3
Publication statusPublished - 1 May 2018
Externally publishedYes


  • Antimicrobial resistance
  • Bacterial evolution
  • Bacterial genomics
  • Carbapenem resistance
  • Enterobacter cloacae

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