DETECTIVE-II: From generation to evolution of multi-drug resistant Gram negative pathogens.

In 2019 the MRC and NSFC funded our DETECTIVE network to study the transmission of Multi-Drug Resistant Gram negative (MDR-GN) bacteria in Chinese Intensive Care Units. Four years later we have shown unimaginable levels of introduction of these pathogens into the clinic from the community, and onward transmission in the ICU. What we do not know is why this is so significantly different from the UK where presence of these pathogens as clinical threats in the ICU is much rarer.

To address this knowledge gap we present DETECTIVE-II. In this proposed project we will study 3 inter-connected objectives:

1) We will monitor the extent to which MDR-GN disseminate from the hospital back out into the community in China and the UK by performing genomic surveillance in ICU patients, patients attending hospital from the community as out-patients, and wastewater samples allowing us to determine the onward fate of clinical MDR-GN outside of the Hospital setting.

2) We will determine if there are different adaptations to the clinical and non-clinical environments in UK and Chinese strains that may explain their differential abundance in the two locations. In particular we believe Chinese strains may be very successful because they are specially adapted to colonising the human gut, much more so than that strains we see rarely in UK Hospitals. We can test this using lab based models of the human gut and competing Chinese and UK strains.

3) We will determine if there are inherent differences in the ability of UK and Chinese strains to acquire and successfully integrate mobile genetic elements. This is a crucial process in bacteria becoming MDR and also acquiring new genes that may make them better at colonising the gut. We can compare the extent to which UK and Chinese strains take DNA from each other and determine if the successful Chinese strains are more prone to taking up and DNA and changing their physical properties as a result.

Together these objectives should provide a definitive analysis of the reasons why MDR-GN pathogens are established as clinical threats in the ICU setting in China but not the UK. We believe our data could identify true clinical-relevant information that could help reduce MDR-GN prevalence in Chinese clinical settings as well as ensure prevalence remains low in UK clinical settings.