Postgraduate research

The role of staphylococcal pyochelin methyltransferase (Spm) in microbial competition and iron uptake

Qualification: PhD

Department: Genetics

Application deadline: 1 September 2022

Start date: 26 September 2022 or later upon agreement

Overview

Supervisors:

Project description:

Many types of infections are polymicrobial in nature, meaning that two or more microbial species coexist and potentially interact with each other. Staphylococcus aureus and Pseudomonas aeruginosa are often co-isolated from chronic wounds and lungs of cystic fibrosis (CF) patients. Both pathogens use several mechanisms to scavenge the essential nutrient iron from the environment (1). One of the mechanisms employed by P. aeruginosa is the production of the siderophore (Greek: ‘iron carrier’) pyochelin (1).  We recently showed that S. aureus is equipped with a mechanism, inactivation of pyochelin by methylation, that is important for its fitness during wound co-infection with P. aeruginosa (2). Methylation of pyochelin is mediated by the novel S. aureus methyltransferase Spm (staphylococcal pyochelin methyltransferase), which results in loss of siderophore activity (loss of iron binding and growth support of P. aeruginosa under iron limited conditions) and reduced intracellular reactive oxygen species production by S. aureus (2). Spm is encoded in a putative operon downstream of the xenosiderophore receptor FhuD1.  FhuD1 and FhuD2 are xenosiderophore receptors and in concert with the FhuCBG transport machinery are used by S. aureus to acquire iron from exogenous hydroxamate siderophores (3). The genetic co-localization of Spm in an operon with FhuD1 implicates that Spm might play a role in xenosiderophore utilization by S. aureus. 

Like S. aureus, members of the Burkholderia cepacia complex (BCC) are frequently isolated from CF patients (4) but little is known about the interspecies relationship of these two CF pathogens. Burkholderia cenocepacia, a member of the BCC, is a known pyochelin producer (5) and therefore Spm is likely to influence S. aureus fitness during competition with B. cenocepacia.

Objectives

In my lab, we are interested in the chemical profile of bacterial interactions to understand how bacterial communities are shaped by natural product biosynthesis and biotransformation. The objective of this PhD project is to gain a detailed understanding of the importance of Spm for S. aureus iron acquisition and bacterial competition.

Aim 1: Elucidate the biological role of staphylococcal pyochelin methyltransferase (Spm) in staphylococcal iron acquisition

Aim 2: Determine the role of the newly identified staphylococcal pyochelin methyltransferase (Spm) during competitive interaction with pyochelin producing bacteria.

The successful applicant will work at the intersection of microbiology and natural product analysis. The student will receive extensive training in molecular microbiology and mass spectrometry techniques including bacterial genetics, whole genome and transcriptome sequencing and analysis, protein overexpression and purification, liquid-chromatography mass spectrometry and molecular networking, Students with an interest in microbiology, molecular biology and mass spectrometry are welcome to apply.

References:

  1. Tyrrell and Callaghan, Microbiology (Reading). 2016 Feb;162(2):191-205
  2. Jenul et al., bioRxiv 2022.04.18.486787
  3. Sebulsky and Heinrichs, J Bacteriol. 2001 Sep;183(17):4994-5000
  4. Scoffone et al., Front Microbiol. 2017; 8: 1592
  5. Butt and Thomas, Front Cell Infect Microbiol. 2017 Nov 6;7:460

 

 

 

 

Funding

Funding

This 3.5-year PhD Studentship provides:

  • UK tuition fee waiver
  • Annual Stipend at standard UKRI rates (£16,062 for 2022/23)
  • RTSG of £5,000 p.a.

*International students must be able to demonstrate that they can fund the difference between UK and International fees for the duration of their study. The difference in fees payable is £16,404 per year of study.

Entry requirements

Entry requirements

Applicants are required to hold/or expect to obtain a UK Bachelor Degree's 2:1 or better (or overseas equivalent) in a relevant subject.  

The University of Leicester English language requirements apply where applicable.

 

Informal enquiries

Informal enquiries

Project enquiries:

Application enquiries:

How to apply

How to apply

Please click on the 'Apply' button at the bottom of the page and select September 2022 from the dropdown menu.

With your application, please include:

  • CV
  • Personal statement explaining your interest in the project, your experience and why we should consider you
  • Degree Certificates and Transcripts of study already completed and if possible transcript to date of study currently being undertaken
  • Evidence of English language proficiency if applicable
  • In the reference section please enter the contact details of your two academic referees in the boxes provided or upload letters of reference if already available.
  • In the funding section please specify that you wish to be considered for the CLS Jenul studentship
  • In the proposal section please provide the name of the project supervisors and the project title (a proposal is not required)

Eligibility

Eligibility

UK and *International applicants

*Applicants holding EU Settled and Pre-Settled status, we will require a UK government share code so that we can verify your status (The share code we require starts with S)  please email your share code together with your application ID to pgradmissions@leicester.ac.uk once you have submitted your PhD application.

*International students must be able to demonstrate that they can fund the difference between UK and International fees for the duration of their study. The difference in fees payable is £16,404 per year of study.

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