Vaccines and antibiotics have been at the forefront in the prevention and treatment of infectious diseases. However, the indiscriminate use of antibiotics has led to the development of antimicrobial resistance (AMR). AMR is a global problem and poses a great threat on our ability to treat infectious diseases. Among the resistance mechanisms, biofilm formation presents a complex challenge due to its structural complexity where bacteria are attached to biotic or abiotic surfaces in a exopolymeric matrix resistant to the action of antibiotics and host immune response. The aim of the proposed project will be to elucidate the molecular mechanism of biofilm disrupting agents and evaluate the synergistic action of these agents with model antibiotics and plant extracts against clinically important Gram-positive and Gram-negative organisms such as Streptococcus mutans, Staphylococcus aureus and Pseudomonas aerigunosa. This is achieved by screening and physicochemical characterisation of several different pharmaceutical excipients as the first line of treatment to weaken and disrupt biofilms.
In addition, projects will involve chemical synthesis of heterocyclic compounds with potential antimicrobial activity followed by their characterisation using physicochemical techniques including NMR, IR and Mass spectroscopy. This will be accompanied with microbiological evaluation of the heterocyclic compounds using routine microbiological assays such as agar diffusion assays and broth dilution assays. The activity against planktonic forms as well as biofilms formed by clinically important micro-organisms will be investigated. Compounds with good microbiological activity will be further evaluated for their mechanism of action.
The mechanistic outcomes form the above studies can only be realised by working with multidisciplinary teams. Therefore, there are ongoing collaborations with medicinal chemists who work closely to synthesise and screen novel heterocyclic compounds and determine selectivity and specificity to the target site and formulation scientists who further develop these novel antimicrobial compounds to take them to the market.
Apart from developing new antimicrobial agents, it is also very important to avoid the indiscriminate use of existing antibiotics as this is also a major factor in the development of antimicrobial resistance (AMR). The alternative strategy is to address AMR would be by studying the clinical effectiveness of antibiotics and vaccines used therapeutically and prophylactically, by undertaking systematic reviews and metaanalyses of existing clinical evidence. These studies aim to guide clinicians on the prudent use of existing antibiotics to avoid the spread of AMR
The above proposed studies have wide applications in pharmaceutical/clinical, food and environmental sectors.
Therefore, the overarching aim of our research is to adopt a holistic and interdisciplinary approach to investigate antimicrobial resistance (AMR), by exploring different but complementary strategies. Hence PhD projects are offered in the following three areas.
- Antimicrobial drug development: design, synthesis and development of novel antimicrobial agents to combat antimicrobial resistance specifically targeting bacterial biofilms. These compounds will be chemically synthesised or obtained from natural sources such as microorganisms and plants.
- Molecular Pharmaceutics: characterization and evaluation of functional excipients to enhance the efficacy of existing antibiotics and to study the genomic response to commonly prescribed antibiotics and pharmaceutical excipients.
- Clinical Pharmacy: evaluation of clinical evidence to determine the effectiveness of antibiotics and vaccines through observational studies, systematic reviews and metanalyses.
Enquiries email name and address:
Dr Ayesha Rahman, Senior lecturer in Pharmaceutical Microbiology.
Email: [Email Address Removed]
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