Ricerc@Sapienza

Pseudomonas (P.) aeruginosa antibiotic resistance represents an increasing threat to global public health as prevents the effective treatment of chronic infections of this pathogen, listed in the top six most threatening bacteria by WHO. Therefore, understanding how this bacterial pathogen resists antimicrobials and identifying novel drug targets is crucial for successful therapeutic interventions.

P.aeruginosa deploys several strategies to resist antibiotics, including the endogenous production of hydrogen sulfide (H2S), recently recognized as a general protective gaseous molecule, which renders multiple bacterial species highly resistant to oxidative stress and host immune responses. However, as the other gaseous molecules NO and CO produced by the host to combat infections, H2S interferes with cellular respiration. P.aeruginosa respiratory chain is highly branched and relies on five terminal oxidases: an aa3-, two cbb3-, a bo3-type and a Cyanide Insensitive Oxidase (CIO).

Relevant to human pathophysiology, CIO belongs to the family of bd type oxidases, key respiratory enzymes that confer bacterial resistance to several types of stresses and promote virulence in some pathogens. Our working hypothesis is that the respiratory chain complexes expression is finely tuned during infection and CIO production endows bacterial aerobic respiration with the ability to resist H2S and the other toxic gaseous molecules.

The present project aims at studying the P.aeruginosa terminal respiratory chain complexes to understand the role played by these enzymes within the framework of host-pathogen relationships.
Research will focus on the oxidase expression profile in H2S, NO, CO P.aeruginosa stressed cells and on the effect of these gases on energy metabolism, evaluated in cell membranes and compared to E.coli as a model system, as well as on the isolation and characterization of CIO to shed light on reaction mechanisms and their pathophysiological relevance.