Genomic and Geographic Context for the Evolution of High-Risk Carbapenem-Resistant <italic toggle="yes">Enterobacter cloacae</italic> Complex Clones ST171 and ST78

ABSTRACT 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 analyse...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	antimicrobial resistance bacterial evolution bacterial genomics carbapenem resistance Enterobacter cloacae Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3dfcf99206394211a225caf126f3c080
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3dfcf99206394211a225caf126f3c080
record_format	dspace
spelling	oai:doaj.org-article:3dfcf99206394211a225caf126f3c0802021-11-15T16:00:26ZGenomic and Geographic Context for the Evolution of High-Risk Carbapenem-Resistant <italic toggle="yes">Enterobacter cloacae</italic> Complex Clones ST171 and ST7810.1128/mBio.00542-182150-7511https://doaj.org/article/3dfcf99206394211a225caf126f3c0802018-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00542-18https://doaj.org/toc/2150-7511ABSTRACT 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 Mid-Atlantic 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. IMPORTANCE Carbapenem-resistant Enterobacter cloacae complex (CREC) has emerged as a formidable nosocomial pathogen. While sporadic acquisition of plasmid-encoded carbapenemases has been implicated as a major driver of CREC, ST171 and ST78 clones demonstrate epidemic potential. However, a lack of reliable genomic references and rigorous statistical analyses has left many gaps in knowledge regarding the phylogenetic context and evolutionary pathways of successful CREC. Our reconstruction of recent ST171 and ST78 evolution represents a significant addition to current understanding of CREC and the directionality of its spread from the Eastern United States to the northern Midwestern United States with links to international collections. Our results indicate that the remarkable ability of E. cloacae to acquire and disseminate cross-class antibiotic resistance rather than virulence determinants, coupled with its ability to adapt under conditions of antibiotic pressure, likely led to the wide dissemination of CREC.Angela Gomez-SimmondsMedini K. AnnavajhalaZheng WangNenad MacesicYue HuMarla J. GiddinsAidan O’MalleyNora C. ToussaintSusan WhittierVictor J. TorresAnne-Catrin UhlemannAmerican Society for Microbiologyarticleantimicrobial resistancebacterial evolutionbacterial genomicscarbapenem resistanceEnterobacter cloacaeMicrobiologyQR1-502ENmBio, Vol 9, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	antimicrobial resistance bacterial evolution bacterial genomics carbapenem resistance Enterobacter cloacae Microbiology QR1-502
spellingShingle	antimicrobial resistance bacterial evolution bacterial genomics carbapenem resistance Enterobacter cloacae Microbiology QR1-502 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 Genomic and Geographic Context for the Evolution of High-Risk Carbapenem-Resistant <italic toggle="yes">Enterobacter cloacae</italic> Complex Clones ST171 and ST78
description	ABSTRACT 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 Mid-Atlantic 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. IMPORTANCE Carbapenem-resistant Enterobacter cloacae complex (CREC) has emerged as a formidable nosocomial pathogen. While sporadic acquisition of plasmid-encoded carbapenemases has been implicated as a major driver of CREC, ST171 and ST78 clones demonstrate epidemic potential. However, a lack of reliable genomic references and rigorous statistical analyses has left many gaps in knowledge regarding the phylogenetic context and evolutionary pathways of successful CREC. Our reconstruction of recent ST171 and ST78 evolution represents a significant addition to current understanding of CREC and the directionality of its spread from the Eastern United States to the northern Midwestern United States with links to international collections. Our results indicate that the remarkable ability of E. cloacae to acquire and disseminate cross-class antibiotic resistance rather than virulence determinants, coupled with its ability to adapt under conditions of antibiotic pressure, likely led to the wide dissemination of CREC.
format	article
author	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
author_facet	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
author_sort	Angela Gomez-Simmonds
title	Genomic and Geographic Context for the Evolution of High-Risk Carbapenem-Resistant <italic toggle="yes">Enterobacter cloacae</italic> Complex Clones ST171 and ST78
title_short	Genomic and Geographic Context for the Evolution of High-Risk Carbapenem-Resistant <italic toggle="yes">Enterobacter cloacae</italic> Complex Clones ST171 and ST78
title_full	Genomic and Geographic Context for the Evolution of High-Risk Carbapenem-Resistant <italic toggle="yes">Enterobacter cloacae</italic> Complex Clones ST171 and ST78
title_fullStr	Genomic and Geographic Context for the Evolution of High-Risk Carbapenem-Resistant <italic toggle="yes">Enterobacter cloacae</italic> Complex Clones ST171 and ST78
title_full_unstemmed	Genomic and Geographic Context for the Evolution of High-Risk Carbapenem-Resistant <italic toggle="yes">Enterobacter cloacae</italic> Complex Clones ST171 and ST78
title_sort	genomic and geographic context for the evolution of high-risk carbapenem-resistant <italic toggle="yes">enterobacter cloacae</italic> complex clones st171 and st78
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/3dfcf99206394211a225caf126f3c080
work_keys_str_mv	AT angelagomezsimmonds genomicandgeographiccontextfortheevolutionofhighriskcarbapenemresistantitalictoggleyesenterobactercloacaeitaliccomplexclonesst171andst78 AT medinikannavajhala genomicandgeographiccontextfortheevolutionofhighriskcarbapenemresistantitalictoggleyesenterobactercloacaeitaliccomplexclonesst171andst78 AT zhengwang genomicandgeographiccontextfortheevolutionofhighriskcarbapenemresistantitalictoggleyesenterobactercloacaeitaliccomplexclonesst171andst78 AT nenadmacesic genomicandgeographiccontextfortheevolutionofhighriskcarbapenemresistantitalictoggleyesenterobactercloacaeitaliccomplexclonesst171andst78 AT yuehu genomicandgeographiccontextfortheevolutionofhighriskcarbapenemresistantitalictoggleyesenterobactercloacaeitaliccomplexclonesst171andst78 AT marlajgiddins genomicandgeographiccontextfortheevolutionofhighriskcarbapenemresistantitalictoggleyesenterobactercloacaeitaliccomplexclonesst171andst78 AT aidanomalley genomicandgeographiccontextfortheevolutionofhighriskcarbapenemresistantitalictoggleyesenterobactercloacaeitaliccomplexclonesst171andst78 AT noractoussaint genomicandgeographiccontextfortheevolutionofhighriskcarbapenemresistantitalictoggleyesenterobactercloacaeitaliccomplexclonesst171andst78 AT susanwhittier genomicandgeographiccontextfortheevolutionofhighriskcarbapenemresistantitalictoggleyesenterobactercloacaeitaliccomplexclonesst171andst78 AT victorjtorres genomicandgeographiccontextfortheevolutionofhighriskcarbapenemresistantitalictoggleyesenterobactercloacaeitaliccomplexclonesst171andst78 AT annecatrinuhlemann genomicandgeographiccontextfortheevolutionofhighriskcarbapenemresistantitalictoggleyesenterobactercloacaeitaliccomplexclonesst171andst78
_version_	1718426960736026624

Genomic and Geographic Context for the Evolution of High-Risk Carbapenem-Resistant <italic toggle="yes">Enterobacter cloacae</italic> Complex Clones ST171 and ST78

Ejemplares similares