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Role of metal resistance in foodborne bacterial disease

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  • Full or part time
    Dr J Morrissey
    Prof J M Ketley
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

About This PhD Project

Project Description

Foodborne infectious diseases are frequent and growing public health problems worldwide (World Health Organisation). Recently there has been an increase in foodborne disease incidence associated with the bacterium, Listeria monocytogenes, which can cause high-level mortality in immunocompromised patients through contamination of foodstuffs, particularly processed meat, and cheese. The food sources are thought to be contaminated in food processing facilities, where L. monocytogenes is known to persist for long periods on different surface materials (Beresford et al, 2001; Chambel et al 2007). The aim of this project is to increase our understanding of L. monocytogenes food-borne infection and disease.

Our recent data show that many isolates of L. monocytogenes associated with food and food processing facilities have acquired plasmids with multiple metal resistance genes. Our data show that these plasmids increase L. monocytogenes resistance for several metals, particularly copper. Why Listeria is acquiring these genes and if they are providing the bacteria with a selective advantage is not understood.

It is likely that these metal resistance genes provide the bacteria with increased resistance to the antimicrobial toxicity of heavy metals. Copper and other metals are used as antimicrobial agents in the food processing and agriculture industries. Furthermore, copper toxicity forms part of the host innate immune system’s antibacterial arsenal, accumulating at sites of infection and acting within macrophages to kill engulfed pathogens. Indeed our data show that acquisition of metal resistance genes in methicillin resistant Staphylococcus aureus (MRSA) promotes survival in macrophages (Purves et al., 2018) increasing the infectivity of these strains compared to typical S. aureus.

Therefore, the aim of this project will be to test our hypothesis that increased metal resistance gives L. monocytogenes a strong advantage, that enables them to persist in food and food processing facilities potentiating food contamination and increasing their virulence.

Objectives

1. Establish the importance of increased metal resistance for L. monocytogenes fitness and persistence on abiotic surfaces used in food processing environments.

2. Determine the global transcriptional response of L. monocytogenes in response to metal stress and how this is effected by the presence of the plasmids.

3. Establish the impact of increased metal resistance on intracellular growth and survival in human cells to assess potential risk for increased infection from this foodborne pathogen.

The student will be part of a lively and friendly interdisciplinary research group and will be trained in a wide range of molecular microbiology techniques including transcriptional analysis, tissue culture, fluorescence and electron microscopy, methods for biofilm analysis and metal analysis.

Eligibility

UK/EU applicants only.

Entry requirements

Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject.

The University of Leicester English language requirements apply where applicable: https://le.ac.uk/study/research-degrees/entry-reqs/eng-lang-reqs/ielts-65

How to apply

Please refer carefully to the application guidance and apply using the online application link at https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp

Project / Funding Enquiries: [Email Address Removed]

Application enquiries to [Email Address Removed]

Closing date for applications: Sunday 12th January 2020

References

1. Purves et al. 2018 A horizontally gene transferred copper resistance locus confers hyper-resistance to antibacterial copper toxicity and enables survival of community acquired methicillin resistant Staphylococcus aureus USA300 in macrophages. Environ Microbiol. 20(4):1576-1589.
2. Zapotoczna et al. 2018. Mobile genetic element-encoded hypertolerance to copper protects Staphylococcus aureus from killing by host phagocytes. (2018) MBio. 9(5). pii: e00550-18.
3. Baker et al., 2011, ‘The Staphylococcus aureus CsoR regulates both chromosomal and plasmid-encoded copper resistance mechanisms,’ Environ. Microbiol. 13:2495-2507.
4. Corbett D, Schuler S, Glenn S, Andrew PW, Cavet JS, Roberts IS. 2011 The combined actions of the copper-responsive repressor CsoR and copper-metallochaperone CopZ modulate CopA-mediated copper efflux in the intracellular pathogen Listeria monocytogenes. Mol Microbiol. Jul;81(2):457-72
5. Chambel L, Sol M, Fernandes, Barbosa M, Zilhao, Barata B, Jordan S, Perni S, Shama G, Adriao A, Faleiro L, Requena T, Pelaez C, Andrew, PW and Tenreiro, R. Occurrence and persistence of Listeria spp. in the environment of ewe and cow's milk cheese dairies in Portugal unveiled by an integrated analysis of identification, typing and spatial-temporal mapping along the production cycle. Intern. J. Food Microbiol. (2007) 116:52-63.
6. Beresford, MR.,Andrew, PW. and Shama, G. Listeria monocytogenes adheres to many materials found in food-processing environments. J. Appl. Microbiol. (2001) 90:1000-1005.



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