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Elucidating the emergence of multi-drug resistant Enterococcus faecium


About This PhD Project

Project Description

The Gram-positive bacterium Enterococcus faecium is a commensal of the intestinal tract of humans and animals. However, over the last two decades a clone of E. faecium, termed clade A1, has emerged in hospitals around the world [1]. Strains from this clone are often resistant to multiple antibiotics, with resistance to the antibiotic vancomycin being most problematic. Indeed, the World Health Organisation has listed vancomycin-resistant Enterococcus faecium as a high priority for research. In addition to antibiotic resistance determinants, clade A1 strains have acquired genetic elements that allow them to efficiently colonise and infect patients [2]. Strains from clade A1 also appear to be more tolerant to disinfectants that are widely used in hospital [3,4]. The ability of E. faecium to rapidly adapt to novel environments is likely due to its ability to its remarkable genomic flexibility and the ability to acquire new genes through horizontal gene transfer [2,5]

In this project we will elucidate the drivers of the success of clade A1 E. faecium strains. We will use state-of-the-art comparative genomics approaches to study the transmission and spread of strains in clinical environments. We will be particularly focusing on the complex dynamics of mobile genetic elements (plasmids and integrative conjugative elements) that carry antibiotic resistance genes. In addition, we will use functional genomics tools like RNA-seq and Tn-seq to identify genes and genetic elements that contribute to antibiotic resistance and tolerance to disinfectants. We will also perform in vitro evolution experiments, combined with whole genome sequencing, to better understand how E. faecium can develop tolerance to disinfectants, particularly alcohols.

This project will uncover novel biological traits in E. faecium that can explain its recent emergence as an important opportunistic pathogen. In addition, it will open up avenues for the development of novel interventions to prevent colonisation of the patient environment and the patient intestinal tract by this particularly robust microbe.


Applicants should have a strong background in microbiology, and ideally with some experience in or affinity with bioinformatics. They should have a commitment to perform high-quality research in the field of antimicrobial resistance and hold or realistically expect to obtain at least an Upper Second Class Honours Degree or equivalent in a relevant subject.

References

1. Guzman Prieto AM, van Schaik W, Rogers MR, Coque TM, Baquero F, Corander J, Willems RJ. Global Emergence and Dissemination of Enterococci as Nosocomial Pathogens: Attack of the Clones? Front Microbiol. 2016 7:788.
2. Lebreton F*, van Schaik W*, McGuire AM*, Godfrey P, Griggs A, Mazumdar V, Corander J, Cheng L, Saif S, Young S, Zeng Q, Wortman J, Birren B, Willems RJ, Earl AM, Gilmore MS. Emergence of epidemic multidrug-resistant Enterococcus faecium from animal and commensal strains. MBio. 2013 4:e00534-13.
3. Guzmán Prieto AM, Wijngaarden J, Braat JC, Rogers MRC, Majoor E, Brouwer EC, Zhang X, Bayjanov JR, Bonten MJM, Willems RJL, van Schaik W. The two-component system ChtRS contributes to chlorhexidine tolerance in Enterococcus faecium. Antimicrob Agents Chemother. 2017;61. pii: e02122-16.
4. Pidot SJ, Gao W, Buultjens AH, Monk IR, Guerillot R, Carter GP, Lee JYH, Lam MMC, Grayson ML, Ballard SA, Mahony AA, Grabsch EA, Kotsanas D, Korman TM, Coombs GW, Robinson JO, Gonçalves da Silva A, Seemann T, Howden BP, Johnson PDR, Stinear TP. Increasing tolerance of hospital Enterococcus faecium to handwash alcohols. Sci Transl Med. 2018; 10. pii: eaar6115.
5. Bayjanov JR, Baan J, Rogers MRC, Troelstra A, Willems RJL, van Schaik W. Enterococcus faecium genome dynamics during long-term asymptomatic patient gut colonization. Microb Genom. 2019 doi: 10.1099/mgen.0.000277.

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