Whole genome sequencing identifies zoonotic transmission of MRSA isolates with the novel mecA homologue mecC
Ewan M. Harrison1, Gavin K. Paterson1, Matthew T.G. Holden2, Jesper Larsen3, Marc Stegger3, Anders Rhod Larsen3, Andreas Petersen3, Robert L. Skov3, Judit Marta Christensen4, Anne Bak Zeuthen4, Ole Heltberg4, Simon R. Harris2, Ruth N. Zadoks5, Julian Parkhill2, Sharon J. Peacock2,6, Mark A. Holmes1*
Keywords: cattle; mecC; MRSA; sheep; zoonosis
DOI 10.1002/emmm.201202413 Received December 21, 2012 Revised February 06, 2013 Accepted February 08, 2013 GSee accompanying article http://dx.doi.org/10.1002/emmm.201302622
Several methicillin-resistant Staphylococcus aureus (MRSA) lineages that carry a novel mecA homologue (mecC) have recently been described in livestock and humans. In Denmark, two independent human cases of mecC-MRSA infection have been linked to a livestock reservoir. We investigated the molecular epidemiology of the associated MRSA isolates using whole genome sequencing (WGS). Single nucleotide polymorphisms (SNP) were defined and compared to a reference genome to place the isolates into a phylogenetic context. Phylogenetic analysis revealed two distinct farm-specific clusters comprising isolates from the human case and their own livestock, whereas human and animal isolates from the same farm only differed by a small number of SNPs, which supports the likelihood of zoonotic transmission. Further analyses identified a number of genes and mutations that may be associated with host interaction and virulence. This study demonstrates that mecC-MRSA ST130 isolates are capable of transmission between animals and humans, and underscores the potential of WGS in epidemiological investigations and source tracking of bacterial infections.
The paper explained
The emergence of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is a major public health concern. Recently, MRSA strains with a novel mecA homologue (mecC), which may go undetected by current diagnostic tests, were described in both livestock and humans suggesting potential zoonotic transmission. Denmark has reported a significant increase in cases of CC130 mecC-MRSA between 2003 and 2011 and two independent human cases of mecC-MRSA infection directly linked to a livestock reservoir have been identified.
We investigated the molecular epidemiology of these livestockassociated mecC-MRSA cases using WGS. Phylogenetic analysis across the entire core genome revealed that the isolates from these cases form two distinct, farm-specific clusters comprising near identical isolates from the human case and from livestock on that farm. Within each cluster, the human and animal isolates only differed by a small number of SNPs, which supports the premise of zoonotic transmission. In-depth genome analysis identified a number of candidate genes and mutations that may be associated with host–pathogen interactions and virulence of this emerging MRSA clone.
Our findings demonstrate that the CC130 MRSA lineage is capable of transmission between animals and humans, further highlighting the role of livestock as a reservoir for MRSA. Our study also underscores the potential of WGS in epidemiological investigations and source tracking of bacterial infections.