Abstract
Genome sequencing is revolutionizing clinical microbiology and our understanding of infectious diseases. Previous studies have largely relied on the sequencing of a single isolate from each individual. However, it is not clear what degree of bacterial diversity exists within, and is transmitted between individuals. Understanding this ‘cloud of diversity’ is key to accurate identification of transmission pathways. Here, we report the deep sequencing of methicillin-resistant Staphylococcus aureus among staff and animal patients involved in a transmission network at a veterinary hospital. We demonstrate considerable within-host diversity and that within-host diversity may rise and fall over time. Isolates from invasive disease contained multiple mutations in the same genes, including inactivation of a global regulator of virulence and changes in phage copy number. This study highlights the need for sequencing of multiple isolates from individuals to gain an accurate picture of transmission networks and to further understand the basis of pathogenesis.
Highlights
Genome sequencing is revolutionizing clinical microbiology and our understanding of infectious diseases
The power of genome sequencing to identify outbreaks and transmission events and to track the source of bacterial pathogens has been exemplified by a number of studies and will become an invaluable tool to inform hospital infection control, in view of the increasing problems posed by multidrug-resistant pathogens[4,5,6,7]
The index case was a 4-year-old German Shepard dog admitted to a veterinary hospital with suspected toxic epidermal necrolysis manifesting in an open abdominal wound
Summary
Genome sequencing is revolutionizing clinical microbiology and our understanding of infectious diseases. Previous studies have largely relied on the sequencing of a single isolate from each individual It is not clear what degree of bacterial diversity exists within, and is transmitted between individuals. This study highlights the need for sequencing of multiple isolates from individuals to gain an accurate picture of transmission networks and to further understand the basis of pathogenesis. Studies to date have largely relied upon sequencing of single colonies from individual hosts, while recent data indicate within-host populations of bacterial pathogens may be heterogeneous. To further understand the cloud of diversity that exists within colonized individuals and during transmission, we undertook deep sequencing of a methicillin-resistant S. aureus (MRSA) ‘outbreak’ at a veterinary hospital involving both staff and animal patients. We highlight the need for sequencing of multiple isolates for the accurate determination of transmission networks
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