Microbiology research study

We invite applications to study for an MSc by Research or PhD.

Combatting antimicrobial resistance: Small-molecule inhibitors (SMIs) as precision anti-virulence agents

Antimicrobial resistance (AMR) is an ever-increasing global issue and it is estimated that deaths associated with AMR infections will exceed 10 million by 2050, superseding cancer as the leading cause of global mortality. Traditional antibiotics display antimicrobial activity through direct targeting of key bacterial cellular processes such as cell wall formation, which are essential for viability but are susceptible to resistance generation. In contrast, one approach to combatting AMR is the development of novel anti-virulence agents, which target pathogen specific virulence traits, such as enzymes involved in the generation of post-translational modifications and epigenetics. We have identified lead SMIs and now aim to use virtual screening, microbiological, cell culture and in vivo assays to determine the anti-virulence effects.

References

Rasko, D.A., and Sperandio, V. (2010) Anti-virulence strategies to combat bacteria-mediated disease. Nat. Rev. Drug Discov., 9, 117-128.

For self-funded PhD and MSc by Research project enquires please contact Dr Jonathan Butler (jonathan.butler@mmu.ac.uk)

Sustainable antimicrobial fabrics for use within wound care management

Healthcare associated infections (HCAIs) are a major cause of morbidity and mortality with MRSA and P. aeruginosa being the prevailing causes of skin and soft tissue infections. It is estimated that between 7% and 10% of hospitalised patients will develop such an infection type. Developing antimicrobial textiles and wound dressings is one method of reducing HCAIs, whilst assisting the healing process and promoting local antisepsis. We have identified natural fabrics with inherent antimicrobial properties against MRSA. Furthermore, we have developed encapsulation technology to sustainably manufacture nanofibres with slow releasing antimicrobial properties. We now aim to develop an applied product to exploit this technology for use within healthcare and commercial applications.

References

Lu, H. et al.(2021) Natural antimicrobial nano composite fibres manufactured from a combination of alginate and oregano essential oil. Nanomaterials, 11(2062), 1-17.

Butler, J.A. et al. (2021) A traditional Ugandan Ficus natalensis bark cloth exhibits antimicrobial activity against Methicillin‐Resistant Staphylococcus aureus. J. Appl. Microbiol., 131(1), 2-10.

For self-funded PhD and MSc by Research project enquires please contact Dr Jonathan Butler (jonathan.butler@mmu.ac.uk)

Novel metallotherapeutics as antimicrobial agents

Antimicrobial resistance is an ever-increasing global problem with very few novel antimicrobial agents being introduced into the clinical setting. Compounds based on metals from the Platinum-group including, Ruthenium (Ru), Rhodium and Platinum have previously been exploited for use in anticancer chemotherapy and are now being explored for use as antimicrobial agents. We have identified several highly active Ru metallotherapeutic compounds, which individually demonstrate potent selective antibacterial activity against multidrug resistant bacterial pathogens including MRSA and P. aeruginosa. This project now aims to validate the potential for use as topical and systemic treatment options and understand the mechanisms of cellular antimicrobial activity by using physical (microscopy), biochemical (cellular leakage assays, membrane permeation assays) and molecular (DNA-binding assays, qRT-PCR, RNA-seq) techniques.

References

Britten, N.S. and Butler, J.A. (2022) Ruthenium metallotherapeutics: novel approaches to combatting parasitic infections. Curr. Med. Chem., DOI: 10.2174/0929867329666220401105444

Southam, H.M. et al. (2017) The microbiology of Ruthenium complexes. Adv. Microb. Physiol., 71, 1-96.

For self-funded PhD and MSc by Research project enquires please contact Dr Jonathan Butler (jonathan.butler@mmu.ac.uk)

Molecular basis for attachment, colonisation and survival of the foodborne pathogen Campylobacter jejuni

Campylobacter jejuni is the worldwide leading cause of human bacterial enteric disease. The molecular mechanisms by which C. jejuni attach, colonise and survive on surfaces, especially during food preparation, are poorly understood. Bipolar flagella play a key role in virulence and are composed of FlaA and FlaB protein subunits. These are extensively modified by glycan sugar moieties during the process of glycosylation, which is implicated in immune evasion and providing structural stability to the flagellum filament. This study will investigate the role of glycosylation in mediating attachment to a range of domestic and industrial food preparation surfaces, in order to help develop novel intervention strategies which reduce the risk of transmission.

References 

Burnham, P.M. and Hendrixson, D.R. (2018) Campylobacter jejuni: collective components promoting a successful enteric lifestyle. Nat. Rev. Microbiol., 16, 551-565.

Hitchen, P. et al. (2010) Modification of the Campylobacter jejuni flagellin glycan by the product of the Cj1295 homopolymeric tract containing gene. Microbiology, 156(7), 1953-1962.

For self-funded PhD and MSc by Research project enquires please contact Dr Jonathan Butler (jonathan.butler@mmu.ac.uk)

Antifouling biometric surfaces

• Vacant until filled

There is a rising interest in the use of antifouling surfaces whose properties are based on the naturally occurring self-cleaning surfaces found in nature. These designs are known as biomimetics.

Many of these surfaces have a range of topographies, chemistries and physiochemistry. The development of such surfaces has the potential for use in the food, water and medical industries to prevent bacterial adhesion and biofilm formation.

The projects based around this subject will focus on:

• producing and analysing these surfaces and test their antifouling properties

• determining the effect conditioning films have on the surfaces

• determine how the different surface features - topography, wettability and physicochemistry - affect the attachment, retention and biofilm formation of bacteria on such surfaces

Supervisors

• Prof Kathryn Whitehead

• Prof Chris van der Gast

Effect of antimicrobial surfaces and metal ions on bacterial survival

• Vacant until filled

There is a requirement to reduce the transmission and infection of patients in clinical settings. And the use of metals as antimicrobials in their ionic form or as surfaces in the medical industry is becoming increasingly popular.

This project will determine the antimicrobial efficacy of different metals and/or metal ions, with respect to their use in biomaterials or on touch surfaces.

We will also examine how the presence of metals affects the antimicrobial resistance of bacteria.

This work may include determining the efficacy of antimicrobial surfaces over time and/or the efficacy of antimicrobial surfaces in the presence of a conditioning film.

SUPERVISORS

• Prof Kathryn Whitehead

• Prof Chris van der Gast

Recovery of bacteria from washing machine components and fabrics

• Vacant until filled

Due to increasing environmental concerns, there has been a concerted effort by industry to provide cleaning formulations that work effectively at lower temperatures.

However, the effect of these on the type of bacteria that attach to washing machine components or clothing is unknown.

It is also unknown if the biocidal use has effects on the residual bacterial such as the development of persisters and/or antimicrobially resistant bacteria.

This project will investigate the type of bacteria recovered from these surfaces, their antibiotic-resistant profiles and their growth on different surfaces in multispecies consortia.

SUPERVISORS

• Prof Kathryn Whitehead

• Prof Chris van der Gast

Antimicrobial resistance of bacteria recovered from water systems

• Vacant until filled

There are a number of surfaces used in the production of utilities that are applied in water systems.

However, it remains unclear:

• which bacteria can be covered from such surfaces

• what their antimicrobial resistance to antibiotics and biocides is

• what their propensity for survival is

This project will investigate aspects of the following themes:

• recovery and identification of bacteria from different surfaces of water systems

• determining antibiotic resistance and understanding how different parameters – including conditioning film, multispecies bacterial consortia, environmental conditions and subjection to cleaners - affect their survival

Supervisors

• Prof Kathryn Whitehead

• Prof Chris van der Gast

Use of proteins to prevent bacterial attachment to surfaces

• Vacant until filled

Surfaces in the medical (biomaterial or high tough surfaces), food or water industries are coated with a layer of organic material after use that is described as a conditioning film. This conditioning film can result in the surface becoming more attractive or more repulsive to bacterial species.

This project will investigate different conditioning films on relevant materials to determine how they increase or decrease microbial attachment.

Applications include the food, medical or environmental sectors.

Supervisors

• Prof Kathryn Whitehead

• Prof Chris van der Gast

Effect of UV on bacterial detection or elimination

• Vacant until filled

Different light wavelengths have the potential to detect bacterial and organic material on surfaces. Under certain circumstances, they can also be used to kill bacteria.

These projects will investigate the effectiveness of a range of lights to detect and/or kill bacteria on different surfaces, and in different matrices such as blood, milk and water, for use in the rapid detection of surface fouling in comparison with current methodologies.

Applications include the food, medical or environmental sectors.

Supervisors

• Prof Kathryn Whitehead

• Prof Chris van der Gast

Antimicrobial activity of novel compounds against bacteria for use in the food, water or medical industries

• Vacant until filled

Antimicrobial resistance (AMR) to commonly prescribed antibiotics is a huge, global health concern.

The recent emergence of multidrug-resistant pathogens has created the need to develop alternative therapies and biocidal alternatives.

To determine which new compounds and biocidal agents are most effective against AMR bacteria, and in which combinations synergy occurs, we need to perform a range of microbial testing.

We will test the compounds alone or in synergy against planktonic and attached cells, with and without organic material, and against microbial biofilms. Complex biofilm modelling will be an integral part of this project.

SUPERVISORS

• Prof Kathryn Whitehead

• Prof Chris van der Gast