After completing her undergraduate degree in Pharmacy, Ayesha studied for a Masters in Applied Biomolecular Technology at the University of Nottingham which was followed by a PhD at the University of Birmingham investigating the molecular pathways in microbial systems which produce medicinally important products such as antibiotics. Having completed her doctoral thesis, Ayesha worked as a Post-doctoral Research Fellow at the University of Birmingham investigating the transcriptional and metabolite response of pathogenic E.coli to acid stress as encountered in the GI tract. Ayesha is registered with the General Pharmaceutical Council and has worked as a community pharmacist both at independent pharmacies and at Lloyds Pharmacy Group. Dr Ayesha S Rahman is currently working as a senior lecturer at the Faculty of Science and Engineering, University of Wolverhampton (UoW). She has current research projects in collaboration with Aston University and University of Birmingham
Areas of expertise include
Her current research focusses on development of antimicrobial compounds to combat antimicrobial resistance. The project aims to investigate the hypothesis that "inclusion of transporter modulators within dosage forms that promote pregastric absorption will result in enhancement of antimicrobial efficacy and reduction in antimicrobial resistance". Ayesha has currently one PhD student working on the above project.
Antimicrobial resistance is a huge problem facing healthcare today. With fewer antibiotics in the developmental pipeline, the need to develop novel antibiotics which are effective against resistant microorganisms is of paramount importance. The aim of the project was to determine whether the inclusion of naturally occurring substance such as amino acids which are required by bacteria for growth increase antibiotic uptake and decrease drug efflux in bacteria. Previously we investigated the effect of antibiotic-amino acid salts in human cells through permeability assays and genomic assessment. Their effect in bacteria was studied in the current project by determining the minimum inhibitory and bactericidal concentration of the agents and performing time kill studies. The aminoacid salts of trimethoprim and ciprofloxacin resulted in an increase in the uptake of the complex when studied in human cells and the activity in bacterial cells was not compromised. The work is being continued to assess the activity of these complexes on bacterial biofilms which pose greater threat and are more resistant to antibiotics than individual cells. It is envisaged that this will have a significant impact on society which is fighting against emerging multidrug resistant superbugs and the pharmaceutical industry which is looking for novel drug candidates.
2. MAIN BODY
Title: Defeat by deceit: A novel strategy to combat antimicrobial resistance in superbugs
Introduction: Antibiotic resistance is being referred to as a global threat which will have a significant/deleterious impact on public health in the coming decades as multidrug resistant microorganisms are emerging at an inexplicable fast rate.
Background: Antibiotic resistance has not only emerged due to the ever-evolving bacterial strategies to survive the impact of antibiotics but also due to negligence on the human counterpart which mainly arises as result of non-compliance caused by side effects. Trimethoprim and Ciprofloxacin are poorly soluble in water which results in low permeability across the GI tract. Amino acids such as D-glutamic acid and D-aspartic acid when added to antibiotics increase the solubility of the drugs which leads to increase in permeability and absorption1.
Need for the research: With hardly any new antibiotics discovered in the last two decades and even fewer in the developmental pipeline, the need to discover new antibiotics or develop existing antibiotics which would treat multi drug resistant microorganisms that cause diseases such as life threatening septicaemia, haemorrhagic colitis etc. is a matter of urgency.
Methods: Different ratios of aminoacid and antibiotics such as 1:1, 1:2, 1:4, and 1:8 were prepared followed by evaluation of antimicrobial efficacy of these aminoacid-antibiotic pairs. Investigations were centred on assessing bacterial growth rate and response upon exposure to antimicrobial formulations.
FINDINGS: Aminoacid-antibiotic pairs showed an increase in permeability in human cells due to overexpression of alternate transporters and retained activity against planktonic E.coli cells2. Currently work is being carried out to test the efficacy of these complexes on biofilms of bacteria which cause wound infections and cystic fibrosis. This will be followed by analysing gene expression changes upon exposure to these agents.
Following on from the ERAS Project Dr Ayesha Rahman (Wolverhampton University) in collaboration with Dr Afzal Mohammed (Aston University – lead applicant) and Quest Healthcare Ltd has been successful in securing a BBSRC funded industrial case award valued at around £98k. The project titled “understanding the mechanistic uptake and exploring the translation of novel amino acid based ion pair complexes” is a four year studentship which will commence in 2015.
The proposed research aims to study the mechanism of permeability enhancement of poorly permeable model drugs in the presence of different concentration of oppositely charged amino acids and evaluate their applicability in reducing drug efflux (human cell models) and antibiotic resistance. Model antibiotics will be tested in the presence of amino acids as ion pairs to study drug efflux as well as evaluate their impact on bacterial biofilms. Results from these investigations will for the first time provide the cellular basis for drug permeation of ion pair based drug delivery and also mechanistic understanding of ion-pair uptake and translational applicability of the concept.