Combating MRSA; increasing our understanding of transmission success will lead to better control of MRSA


Research Project: 2017-06-01 - 2021-06-30
Total sum awarded: €1 261 462

The primary aims of the MACOTRA project are three-fold 1.To develop and provide a framework for evaluating differences in transmission of MRSA. 2. To unravel the different contributions to MRSA clonal success on a genetic and population level. 3. To develop a mathematical model which predicts and unravels the rise and shine of clones. Study material will be epidemiologically well-defined isolates from international collections, and microbiomes from patients. Study questions are from the bacterial point of view; • To delineate factors for unsuccessful and successful (epidemic) clonal MRSA, from both livestock and human isolates from the Netherlands, UK and France From the human point of view; • To study the role of MRSA carriage in relation to microbiome of nose and skin. From the interaction between the host and bacteria • To develop in-vitro models to study differences in strain survival and transmission in the host and in response to decolonisation, antibiotics, disinfectants and microbiome. Skin, plasma and microbiome models will be used. • To develop deterministic and individual-based mathematical models of bacterial dynamics, including survival, within human hosts, as well as on transmission dynamics between human hosts. MACOTRA study results and data from decolonisation and other intervention strategies, risk groups and antibiotic/disinfectants usage in the Netherlands, UK and France will serve as input to the mathematical models. The consortium exists of (molecular) microbiologists, medical doctors and mathematical modellers, all very successful and well-known in the MRSA and / or infectious disease field; from basic research to clinical (intervention) studies.

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  • Margreet Vos, Erasmus MC University Medical Center, Netherlands (Coordinator)
  • Jodi Lindsay, St George's University of London, United Kingdom (Partner)
  • Gwenan Knight, Liverpool School of Tropical Medicine, United Kingdom (Partner)
  • Leo Schouls, National Institute for Public Health and the Environment (RIVM), Netherlands (Partner)
  • Gerard Lina, Universite Claude Bernard Lyon 1, France (Partner)

Staphylococcus aureus is a microorganism that colonizes the skin in 10-35% of healthy individuals. Methicillin-resistant S. aureus (MRSA) is characterized by clonal spread. MRSA clones are unequally distributed across the world and different clones are dominant at different times. The MACOTRA project studied the interaction between MRSA, humans and the environment. We used mathematical model to gain a better understanding of MRSA dynamics. A collection of ~300 MRSA strains was genetically characterized, highlighting antimicrobial genes possibly contributing to successful transmission. Different clones were successful in different countries, partly due to antimicrobial resistance gene carriage and antimicrobial usage. Antimicrobial resistance genes transferred easily between some isolates and we identified that bacteriophage – viruses of bacteria – were responsible. Evaluation of MRSA survival under dehydrated conditions or on a human skin mimic showed similar results for epidemic and sporadic MRSA. Survival on a dry environment could not explain success of different clones. Our study of nasal samples from volunteers showed that the bacterial composition of the nose was slightly different in S. aureus carriers compared to noncarriers. Mathematical models suggested that the established dominant clone in a particular country will be maintained as the dominant clone over time. A main predictor of success was antimicrobial resistance, driven by antibiotic use. Other important factors for success were not identified yet. To enhance international epidemiological surveillance and subsequent data collection, we presented a proposal for harmonisation of MRSA surveillance.