Doherty Institute - Research Publications

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Author: Tong, Steven × Author: Williamson, Deborah × End date: 2019 × Start date: 2016 ×

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    Comparative M-protein analysis of Streptococcus pyogenes from pharyngitis and skin infections in New Zealand: Implications for vaccine development
    Williamson, DA ; Smeesters, PR ; Steer, AC ; Morgan, J ; Davies, M ; Carter, P ; Upton, A ; Tong, SYC ; Fraser, J ; Moreland, NJ (BIOMED CENTRAL LTD, 2016-10-12)
    BACKGROUND: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are responsible for a significant disease burden amongst Māori and Pacific populations in New Zealand (NZ). However, contemporary data are lacking regarding circulating group A Streptococcal (GAS) strains in NZ. Such information is important in guiding vaccine development. METHODS: GAS isolates from April to June 2015 were recovered from skin and pharyngeal samples from children living in areas of high social deprivation in Auckland, NZ, a significant proportion of which are Māori or Pacific. These children are among the highest risk group for developing ARF. Isolates were compared to concurrently collected pharyngeal isolates from Dunedin, NZ, where both the proportion of Māori and Pacific children and risk of developing ARF is low. Emm typing, emm cluster typing and theoretical coverage of the 30-valent vaccine candidate were undertaken as previously described. RESULTS: A high diversity of emm types and a high proportion of emm-pattern D and cluster D4 isolates were detected amongst both skin and pharyngeal isolates in children at high risk of ARF. Pharyngeal isolates from children at low risk of ARF within the same country were significantly less diverse, less likely to be emm pattern D, and more likely to be theoretically covered by the 30-valent M protein vaccine. CONCLUSIONS: The high proportion of emm pattern D GAS strains amongst skin and pharyngeal isolates from children at high risk of ARF raises further questions about the role of skin infection in ARF pathogenesis. Emm types and emm clusters differed considerably between ARF endemic and non-endemic settings, even within the same country. This difference should be taken into account for vaccine development.
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    Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent
    Steinig, EJ ; Duchene, S ; Robinson, DA ; Monecke, S ; Yokoyama, M ; Laabei, M ; Slickers, P ; Andersson, P ; Williamson, D ; Kearns, A ; Goering, RV ; Dickson, E ; Ehricht, R ; Ip, M ; O'Sullivan, MVN ; Coombs, GW ; Petersen, A ; Brennan, G ; Shore, AC ; Coleman, DC ; Pantosti, A ; de Lencastre, H ; Westh, H ; Kobayashi, N ; Heffernan, H ; Strommenger, B ; Layer, F ; Weber, S ; Aamot, HV ; Skakni, L ; Peacock, SJ ; Sarovich, D ; Harris, S ; Parkhill, J ; Massey, RC ; Holden, MTG ; Bentley, SD ; Tong, SYC ; Planet, PJ ; Torres, VJ (AMER SOC MICROBIOLOGY, 2019-11-26)
    The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere.IMPORTANCE The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant Staphylococcus aureus lineage first isolated from Bangladesh and India in 2004. In this study, we showed that the Bengal Bay clone emerged from a virulent progenitor circulating on the Indian subcontinent. Its subsequent global transmission was associated with travel or family contact in the region. ST772 progressively acquired specific resistance elements at limited cost to its fitness and continues to be exported globally, resulting in small-scale community and health care outbreaks. The Bengal Bay clone therefore combines the virulence potential and epidemiology of community-associated clones with the multidrug resistance of health care-associated S. aureus lineages. This study demonstrates the importance of whole-genome sequencing for the surveillance of highly antibiotic-resistant pathogens, which may emerge in the community setting of regions with poor antibiotic stewardship and rapidly spread into hospitals and communities across the world.