Development, evaluation and translation of next-generation sequencing tools to track MRSA transmission pathways (360G-Wellcome-094882_Z_10_Z)

Nosocomial pathogens represent one of the most significant challenges to the successful delivery of modern medical care. Revealing the routes of transmission and spread of nosocomial pathogens at local, regional, national and international levels is crucial to targeted control. This is severely constrained, however, by the inability to discern between strains of the same epidemiologically successful lineage. For example, two lineages of methicillin-resistant Staphylococcus aureus (MRSA) termed EMRSA-15 and -16 have become disseminated throughout the UK and cause most cases of MRSA infection, but current bacterial typing methods fail to distinguish between strains of the same lineage. This technology gap represents a major hindrance to the development of more effective infection control strategies since transmission of MRSA between patients and healthcare facilities cannot be differentiated from independent acquisition. We have developed a series of novel and synergistic tools to type, map and track nosocomial pathogens and to determine genetic events associated with shifts in patterns of transmission and infection. This involves the integrated use of whole genome sequence typing (which we have already shown to be capable of defining detailed phylogenetic structuring within a single MRSA lineage), a web-based interface that provides mapping and interactive tree building to place a given strain within its geographical and phylogenetic context, and a network model of patient movement between NHS facilities. The goal of this Consortium is to apply these tools to define transmission of ERMSA-15 and -16 at local and national levels in the UK, and to have demonstrated a clear role for this approach in disease control by the end of the grant. Our strategy is to build upon an existing grouping of internationally recognized scientists who have developed these tools, and to expedite their rapid introduction into UK healthcare systems. Our objectives are to undertake a 3-stage programme of research (development, evaluation and implementation) in which we refine and further develop these tools, conduct prospective macro- and micro-epidemiological evaluation studies, and seek to integrate this technology into the healthcare infrastructure. The detailed reconstruction of MRSA transmission pathways would be predicted to have a dramatic effect on future strategies for control and prevention of nosocomial MRSA infection. Furthermore, our model is adaptable to other existing and emerging pathogens, and will strengthen the capacity and resilience of healthcare networks to control and prevent a spectrum of current and future infectious disease threats.