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
PROBLEM:
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.
RESULTS:
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.
IMPACT:
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.
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