Professor Raechelle D'Sa

Nitric oxide (NO) is a potent broad spectrum antimicrobial and part of the body’s defense mechanism that is activated by inflammatory cells (neutrophils and macrophages) which are responding to invading pathogens such as bacteria, protozoa, and fungi. Due to the plurality of mechanisms responsible for bacterial inactivation, there is a low tendency for the bacteria to develop antimicrobial resistance. Additionally, NO is also effective against both planktonic bacteria and biofilms, the latter of which are notoriously difficult to treat due to the presence of an exopolysaccharide matrix that is resistant to penetration by antibiotics. This is a major research stream in our laboratory and we have developed nitric oxide releasing platforms (nanoparticles, gels, surfaces) for treating infections in the eye, skin and bone.

Antimicrobial Peptides (AMPs) are produced by all complex organisms as well as some microbes as part of innate immune response, and display diverse and complex antimicrobial activities against a broad range of Gram negative and Gram positive bacteria, including those resistant to established antibiotic drug therapies, mycobacteria, enveloped viruses, parasites and fungi. They have gained increasing popularity as a possible alternative to antibiotics due to their broad spectrum activity, low toxicity and most importantly their low tendency to induce antimicrobial resistance (AMR). The covalent immobilization or encapsulation of these AMPs has the potential to improve efficacy and localized availability. We are developing nanodelivery vehicles of these AMPs for the treatment of surgical site infections.

Metals have served as antimicrobial agents for a very long time, yet for most of history, their mechanisms of action have been shrouded in mystery. Recent research suggests that various metals inflict specific and separate forms of harm on microbial cells, such as oxidative stress, protein malfunction, or damage to the cell membrane.

Bioinspired antimicrobials

Healthcare-acquired infections (HCAI) can develop as a result of healthcare interventions such as medical or surgical treatment, or from the interactions with healthcare staff and facilities. The ability to treat these infections is becoming increasingly problematic as the overuse of antibiotics to date has caused common pathogenic microorganisms to develop mechanisms for antimicrobial resistance (AMR). The rapid spread of these drug resistant microorganisms has caused traditional antimicrobial agents to become less effective. Chronic infections require long term therapeutic solutions and drug delivery devices that can be implanted or used as patches have the potential to reduce to deliver the dose of the drug in a sustained and controlled manner over extended periods, while eliminating the risk of patient non-compliance in taking oral medications. Moreover, these site-specific implantation techniques can circumvent systemic toxicity issues and result in a higher concentration of drug at the target site.

There are several implantable drug delivery devices on the market today, however these are manufactured using non-biodegradable polymers which would need surgical removal once the reservoir is exhausted. The use of biodegradable polymers would bypass the requirement for surgical removal. Additive manufacturing processes such as 3D printing and electrospinning are promising in the development of highly controlled formulations which can be individualised to specific patients.

Biomanufacturing of antimicrobial drug delivery platforms

The introduction of sand filtration and chlorine disinfection marked the end of waterborne epidemics in the developed world over a century ago. Nevertheless, unexpected surges in waterborne disease outbreaks persist. Globally, in many developing nations, waterborne diseases continue to be the primary cause of death. While the current disinfection methods employed in drinking water treatment can effectively manage microbial pathogens, recent research has unveiled a conundrum: a conflict between effective disinfection and the creation of harmful disinfection byproducts. The rapid advancements in nanotechnology have ignited substantial interest in employing nanomaterials for water disinfection. These nanomaterials, owing to their large surface area and high reactivity, prove to be exceptional adsorbents, catalysts, and sensors. More recently, various natural and engineered nanomaterials have also demonstrated potent antimicrobial properties.

We are currently investigating disinfection of water systems including drinking water supplies, industrial water systems and marine applications

Nanomaterials for infection control in water systems