With an estimated annual incidence of 11 million, severe burns are the fourth most common type of trauma in the world, and in many cases life-threatening. Wound infection is one of the main causes of death in burn victims. Staphylococcus aureus is one of the bacteria most often responsible for these fatal infections. S. aureus is an opportunistic pathogen capable of producing an impressive arsenal of virulence factors enabling it to evade the immune system. In addition, S. aureus forms biofilms that envelop the bacteria in a matrix within which they adapt their metabolism to persist, enhancing their tolerance to antibiotics. The spread of S. aureus strains resistant to first-line antibiotics represents an additional threat. These properties make S. aureus infections more difficult to eradicate. Therefore, there is an urgent need to identify new antibacterial approaches that could complement conventional medical treatment.
This thesis aims to study the effects of cold atmospheric plasma (CAP) on the healing of infected burns, in particular its influence on S. aureus biofilm. CAP is an ionized gas that produces a mixture of electrons, ions, and reactive species. While CAP antibacterial and anti-biofilm effects have been reported, the molecular mechanisms driving these processes have not been characterized. The anti-biofilm potential of CAP and its synergy with antibiotics, which are already used in the clinic or under development in our group, will be assessed in models of increasing complexity in vitro, ex vivo, in vivo and in a preclinical model in large animals. The molecular mechanisms behind the action of CAP will be deciphered through a transcriptomic approach and the most promising pathways will be investigated further using mutants.
