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Development of a rapid screening method for Carbapenemase-resistant Enterobacteriaceae using volatile and non-volatile metabolite profiles


Project Description

Nosocomial infections caused by Enterobacteriaceae are a major concern to clinicians. Species include Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae, all of which are prevalent in ventilator-associated pneumonia. Drug resistance, particularly for ESBL-producing Enterobacteriaceae, is usually circumvented with combination therapy consisting of a beta-lactam drug and a beta-lactamase inhibitor. However, Enterobacteriaceae are becoming resistant to carbapenems, often said to be the “last resort” antimicrobial, and categorised as an urgent threat by the US Centre for Disease Control (2003). There are currently three classes of carbopenem-resistance enzymes known (Class A carbapenemases, Class B Metallo-β-lactamases, and Class D OXA carbapenemases), which are further divided into several subgroups dependant on the microorganism.

Volatile and non-volatile metabolites have shown to be useful in discriminating bacteria. In this research project, the student will sample headspace and extracellular metabolites from pure cultures to describe a core and resistant metabolite profile. This may also involve isotopic enrichment for metabolic flux analysis. The student will then perform complex univariate and multivariate analyses to develop robust classification algorithms and compare these to commonly used clinical microbiology tests.

Candidate metabolite biomarkers may potentially be used for clinical diagnosis where the student will analyse patient sputa and perform targeted analysis on exhaled breath data from a recent clinical study. The work may lead to developing an assay or screening method for clinical use, which can guide personalised dosing and antimicrobial choice.

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject. Candidates with experience in microbiology, and analytical chemistry, alongside an interest and aptitude in multivariate data analysis, are encouraged to apply.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

https://www.cdc.gov/drugresistance/biggest-threats.html

Ahmed WM, Geranios P, White IR, Bromley M, Lawal O, Nijsen T, Goodacre R, Read N, Fowler SJ. Development of an adaptable headspace sampling method for metabolic profiling of the fungal volatome. Analyst 2018 DOI: 10.1039/C8AN00841H

Lawal O, Knobel H, Weda H, Bos LD, Nijsen TME, Goodacre R, Fowler SJ. Volatile organic compound signature from co-culture of lung epithelial cell line with Pseudomonas aeruginosa. Analyst. 2018 Jul 7;143(13):3148-3155. doi: 10.1039/c8an00759d.

Lawal, O., Knobel, H., Weda, H. Nijsen TME, Goodacre R, Fowler SJ. TD/GC–MS analysis of volatile markers emitted from mono- and co-cultures of Enterobacter cloacae and Pseudomonas aeruginosa in artificial sputum Metabolomics 2018 14: 66. doi.org/10.1007/s11306-018-1357-5

Ahmed WM, Lawal O, Nijsen TM, Goodacre R, Fowler SJ. Exhaled Volatile Organic Compounds of Infection: A Systematic Review. ACS Infect Dis. 2017;3:695-710. doi: 10.1021/acsinfecdis.7b00088

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