Location: Virus and Prion Research
Project Number: 5030-32000-109-11-A
Project Type: General Cooperative Agreement
Start Date: May 1, 2014
End Date: Oct 1, 2015
1) Obtain draft whole-genome sequences of 110 ST5 strains isolated from human, animal, and environmental samples. 2) Compare the draft genome sequences obtained to generate a more comprehensive assessment of the origin, evolution, and zoonotic potential of these strains. 3) Use in vitro binding assays to test the capacity of the strains to adhere to human and porcine keratinocytes.
Recent publications have demonstrated that the livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) strains obtained from swine and swine production facilities are more genetically diverse than the first reported sequence type ST398. This appears particularly true in the United States, where methicillin-resistant Staphylococcus aureus (MRSA) ST5 is more commonly being found in swine facilities. Several studies have demonstrated a genetic basis for reduced human infection with ST398. Unfortunately, genetic studies similar to the ones performed on ST398 strains have not been conducted on these MRSA ST5 strains and so it remains unclear whether or not ST5 strains have the capacity to colonize and cause disease in humans. To address this question, we propose to perform whole-genome sequence comparative analysis using 110 ST5 strains encompassing both methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA strains from both human and animal populations. These isolates were obtained from swine, swine farms and production facilities, individuals who transiently visited swine farms (veterinary students), and from individuals with long-term exposure to diverse swine farms (veterinarians). Additionally, we propose to test the ability of these ST5 strains to adhere to both human and swine cells. The combined results from the proposed genomic and attachment assays will provide a comprehensive evaluation of the origin, evolution, and zoonotic potential of LA-MRSA strains. The combined genomic and phenotypic results will also enable us to measure the risk of these strains in causing a public health concern as well as understanding more clearly the pathogenic features of Staphylococcus aureus (S. aureus) in humans and animals.