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Investigating predatory bacteria in combination with antibiotics for the treatment of drug-resistant polymicrobial infections S&T48

  • School: School of Science and Technology
  • Study mode(s): Full-time / Part-time
  • Starting: 2022
  • Funding: UK student / EU student (non-UK) / International student (non-EU) / Fully-funded

Overview

NTU's Fully-funded PhD Studentship Scheme 2022

Project ID: S&T48

Antimicrobial resistance is one of the greatest threats facing modern medicine. Many clinically important pathogens are now resistant to frontline antibiotics. The current situation demands that novel alternatives to antibiotics are investigated, with priority placed on approaches effective against drug-resistant bacteria.  One such alternative is the use of the predatory bacterium Bdellovibrio bacteriovorus. B. bacteriovorus is a small Gram-negative bacterium that naturally preys on and kills other Gram-negative bacteria as part of its life cycle. Several medically important, drug-resistant bacteria have been shown to be killed by B. bacteriovorus in vitro, including all Gram-negative members of the ESKAPE pathogens which are the leading cause of life-threatening, hospital-acquired infections.  Although the use of B. bacteriovorus holds much promise, it is limited by the organism’s restriction to Gram-negative prey. In a clinical setting, infections are often caused by a consortium of bacteria, comprising of both Gram-negative and Gram-positive isolates.

Therefore, this project will aim to develop a novel approach for the treatment of polymicrobial infections by combining predatory bacteria (Bdellovibrio) with Gram-positive antibiotics. The project will take a translational approach, beginning with in vitro lab based assays to confirm efficacy against a range of pathogens and investigate optimal combinations / doses of predator and antibiotic(s).  Results from this initial phase will identify top candidates to take forward for study in a collagen wound model of polymicrobial infection. This model provides a biochemically and histologically relevant system to further characterise the dynamics of this novel therapy using a range of techniques including fluorescence microscopy. Finally, in vivo efficacy will be tested using a Galleria mellonella model of systemic infection. G. melloella possesses a rudimentary innate immune system similar to that found in humans. Therefore, the host immune response to this novel therapy can also be monitored.

The well characterised innate-immune system of G. mellonella provides an opportunity to study how B. bacteriovorus interacts with components of the host immune system. Key G. mellonella genes, known to be expressed during infection, will be monitored using real-time quantitative PCR (qPCR) upon exposure to both pathogenic bacteria and B. bacteriovorus. Complementary to this, expression of B. bacteriovorus genes known to be involved in both the B. bacteriovorus stress response and predation may be studied by both qPCR and transcriptomic techniques e.g. RNA-Seq.

School strategic research priority

The project aligns with NTU’s Health and Wellbeing theme which aims to tackle some of the major health issues facing society. The research aligns with that of the Centre for Health, Ageing and Understanding Disease under the research theme of Antimicrobial Resistance, Omics & Microbiota

Entry qualifications

For the eligibility criteria, visit our studentship application page.

How to apply

For guidance and to make an application, please visit our studentship application page. The application deadline is Friday 14 January 2022.

Fees and funding

This is part of NTU's 2022 fully-funded PhD Studentship Scheme.

Guidance and support

Download our full applicant guidance notes for more information.

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