Title: Antibiofilm Wound Dressings Designed to Prevent Infection and Minimize the Risk of Bacteraemia and Sepsis
Funder: The Academy of Medical Sciences

Abstract: The aim of this proposal is to develop novel burn wound dressings that will inhibit infection and minimise the risk of bacteraemia and sepsis. The first objective is to identify antibiofilm compounds that can maintain their activity when integrated into hydrogel wound dressings. The second objective will be to determine the in vivo efficacy of the antibiofilm hydrogel wound dressings. This proposal will focus specifically on inhibiting burn wound colonisation by Pseudomonas aeruginosa, one of the most common and difficult to treat burn wound pathogens. P. aeruginosa’s ability to form recalcitrant biofilms is linked to wound dressing failure and burn wound sepsis. The first part of the proposal will focus on identifying compounds that can disrupt the key signalling pathways that control biofilm formation. A suite of targeted genetic biosensors will be used for this and a key go/no-go criterion will be identifying compounds that disrupt these pathways without impacting growth. Thus, the ability of P. aeruginosa to develop resistance to these compounds will be minimal compared to traditional bactericidal antibiotics. The top-ranking candidates from this screen will be integrated into hydrogels, the primary component of many commercial burn wound dressings and their in vitro antibiofilm activity determined. The top performing antibiofilm hydrogels will then be tested in vivo using a highly innovative Galleria mellonella burn wound model. This model of burn wound trauma and concomitant infection will be used to determine the capacity of our antibiofilm wound dressings to prevent the transition from wound infection to bacteraemia.

Lay abstract: Almost all people at some point in their lives will experience a burn. Many of these burns are minor and can be remedied with a simple plaster to prevent infection. However, for individuals whose burns are large or deep enough to require a hospital visit, they run a higher risk of the burn wound becoming infected. In fact, infection is the leading cause of death among burn patients. A number of different types of bacteria can colonise a burn wound but the most common and serious is Pseudomonas aeruginosa. P. aeruginosa can only cause infection in people whose immune system has been compromised. In burn patients, a key part of the immune system, the skin, has been damaged, which allows bacteria entry into the body. Burn patients who become colonised with P. aeruginosa only have a 20% chance of survival. This is due to P. aeruginosa’s ability to resist antibiotics and to form a community called a biofilm at the burn wound site. Bacteria, like people, do not like to live alone, they like to come together in communities, because just like people living in towns and cities, bacteria in a community are better protected from unfavourable environmental conditions. If we can stop P. aeruginosa forming a biofilm community in a burn wound, we can dramatically increase patient survival. In this proposal, we will develop new wound dressings that specifically stop bacteria forming biofilm communities in burn wounds and test them in a new insect burn wound model.

Research activity codes: 5.3 MEDICAL DEVICES
Health categories: INFECTION