Research in Focus: A New Weapon Against Pseudomonas aeruginosa
We interviewed Bhavik Bharochia, a PhD student from the University of Southampton, to learn about his work, which focuses on preventing the severity of biofilm infections, specifically in cystic fibrosis disease states.
My research sits within the healthcare and pharmaceuticals sector. I’m investigating Pseudomonas elastase as a virulence target of Pseudomonas aeruginosa biofilm infections in cystic fibrosis disease states. The project is funded by the Medical Research Council and I collaborate with a biopharmaceutical SME based in France called ANTABIO. The business is focused on drug discovery to treat antimicrobial resistant infections in areas of critical need.
What is the current market position or situation within you sector?
We’re experiencing a generational gap in the development of antibiotics. Since 1962, no new classes of antibiotics have been bought to market to treat some of our most deadly gram-negative bacterial infections. Since 1984, not a single new class of antibiotic has been bought to the market. It’s been projected that antimicrobial resistance will contribute to more deaths than cancer by 2050, leading to a huge economic incentive to develop new resistance breaking drugs. To do this, organisations like ANTABIO, the company I collaborate with, are focusing on the most important life-threatening infections, often termed ESKAPE pathogens. Most importantly, Metalloenzymes, which are attributable to some of the most prominent forms of antimicrobial resistance. I’m interested in bacterial virulence, which impacts the progression of the disease in many patients, and I am trying to target this, and inhibit or prevent the virulence from progressing the infection.
What current unmet need does this research address?
Currently Pseudomonas aeruginosa infections in cystic fibrosis are considered chronic, and we have no effective treatment for these patients apart from attempted eradication, or removal of the bacteria from the patients’ lungs. Biofilms and bacteria within biofilms are incredibly adaptable and they can rapidly evolve resistance to many antibiotics, and are also incredibly tolerant against those which are used for treatment. The work on the elastase inhibitor programme, is a novel method by which we would revolutionise the way we target and treat these infections, not looking at just eradicating the infections, but to prevent the disease progression by stopping the mechanisms of virulence that cause the damage in the lungs of these patients.
How do you see your work as distinctive to other research in your field?
There has been quite a lot of research into quorum sensing inhibition, or preventing the bacteria from communications with each other, which is very similar to what I am looking at, which is actually preventing the bacteria from releasing enzymes, which can then cause damage, which are a product of the cell-to-cell communication methods. This too is an adjunctive approach, however investigating proteins which are specifically related to the disease progression allows us to develop much more specific drugs, with better tolerance for patients, and also lower non-specific effects, which allows us to better understand, study and monitor the disease progression state of these patients.
If successful, the elastase inhibitors will allow us to develop a new weapon in this ever-expanding arsenal against Pseudomonas aeruginosa infections in cystic fibrosis patients. This could also change the way we target these chronic biofilm infections, not only through the eradication therapy but through adjunctive therapies, which prevent the disease progression.
Have any key milestones been completed or targets achieved?
Through my PhD I have successfully contributed to a clinical study, which we held here at the University of Southampton, in collaboration with University Hospital Southampton. This had led to a much greater understanding of the elastase landscape, and has resulted in a very large number of downstream experiments, which are revealing some very exciting data, and I’m sure we’ll see more of this in the future. I have also successfully completed a three-month placement at ANTABIO, where I worked on some of the drug development pipeline, as well as some of the non-Good Laboratory Practice (GLP) studies, which have all contributed to the development of this drug.
Scanning electron microscopy image (3000x mag, 10.5mm WD) of Pseudomonas aeruginosa biofilm aggregates (green) on ciliated (yellow) and differentiated human primary epithelial cells (blue) grown at an air liquid interface in vitro.
I have been quite heavily involved in the delivery of the annual science and engineering day which we host at the University of Southampton. This is a fantastic opportunity to engage with the general public and discuss the research that we’re currently doing in-house in our lab, and also highlight the exciting opportunities that lay ahead in our field in the study of biofilms and microorganisms.
Find out more
If you are interested in learning more about this project and would like to connect with Bhavik please contact NBIC at firstname.lastname@example.org.
Bhavik Bharochia, PhD student with the University of Southampton.