Reconstruction of polymicrobial interactions in infections: the case of Pseudomonas aeruginosa and Candida albicans cross talk in ventilator-associated pneumonia

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Project funded by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID)

Motivation and Goal

Ventilator-associated pneumonia (VAP) is one of the most frequent hospital-acquired infections occurring in mechanically ventilated patients, with 20–70% crude mortality and 10–40% estimated attributable mortality. Risk factors for VAP include advanced age, immunosuppression, broad-spectrum antibiotic exposure, previous hospitalization or residence in a chronic care facility and prolonged duration of invasive mechanical ventilation.
The principal determinant of VAP development is the presence of the endotracheal tube, which enables the leakage of contaminated oropharyngeal secretions down to the lungs, and is vulnerable to colonisation by biofilm producing bacteria. The emergence and dissemination of antibiotic resistance traits in causal agents of this infection and the co-infection by multiple agents reduce treatment options, and are often associated with clinical deterioration and death.
Novel research on VAP therapeutics is looking into quorum-sensing (QS) systems, i.e. drugs targeting the diffusible signals responsible for the expression of virulence and resistance genes. Yet, species cross-talk in co-infection, also dependent on QS molecules, is still poorly studied. The main focus of this exploratory project is to reconstruct the interplay modulating the bacterial fungal cross-talk between Pseudomonas aeruginosa and Candida albicans in VAP infection.
Biofilms

Biofilms

High-throughput biofilm formation and susceptibility assays.

Transcriptomics

Transcriptomics

Analysis of monospecies and mixed biofilms.

microscope

PNA-FISH

Probe development and evaluation.

In silico reconstruction

In silico reconstruction

Reconstruction of experimental results on QS therapeutics.

Reconstructed knowledge