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J Clin Microbiol. 2019 Oct 2. pii: JCM.01261-19. doi: 10.1128/JCM.01261-19. [Epub ahead of print]

A complete genome screening program of clinical methicillin-resistant Staphylococcus aureus isolates identifies the origin and progression of a neonatal intensive care unit outbreak.

Author information

1
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
2
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
3
Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
4
Department of Pathology, Clinical Microbiology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
5
Department of Medicine, Division of Infectious Diseases, Northwell Long Island Jewish, New York.
6
Division of Neonatology and Department of Pediatrics, The Children's Hospital of Philadelphia and The University of Pennsylvania, Philadelphia, PA.
7
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA harm.vanbakel@mssm.edu.

Abstract

Whole-genome sequencing (WGS) of Staphylococcus aureus is increasingly used as part of infection prevention practices. In this study we established a long-read technology-based WGS screening program of all first-episode MRSA blood infections at a major urban hospital. A survey of 132 MRSA genomes assembled from long reads enabled detailed characterization of an outbreak of a CC5/ST105/USA100 clone among 18 infants in a neonatal intensive care unit (NICU) lasting several months. Available hospital-wide genome surveillance data traced the origins of the outbreak to three patients admitted to adult wards during a 4-month period preceding the NICU outbreak. The pattern of changes among complete outbreak genomes provided full spatiotemporal resolution of its progression, which was characterized by multiple sub-transmissions and likely precipitated by equipment sharing between adults and infants. Compared to other hospital strains, the outbreak strain carried distinct mutations and accessory genetic elements that impacted genes with roles in metabolism, resistance and persistence. This included a DNA-recognition domain recombination in the hsdS gene of a Type-I restriction-modification system that altered DNA methylation. RNA-Seq profiling showed that the (epi)genetic changes in the outbreak clone attenuated agr gene expression and upregulated genes involved in stress response and biofilm formation. Overall our findings demonstrate the utility of long read sequencing for hospital surveillance and for characterizing accessory genomic elements that may impact MRSA virulence and persistence.

PMID:
31578260
DOI:
10.1128/JCM.01261-19
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