Abstract

Pseudomonas aeruginosa is one of the major causes of morbidity and mortality of cystic fibrosis patients. During the infection, the bacteria colonize the nutritional rich lung mucus, which is present in the airway secretions in the patients, and they adapt their phenotype accordingly to the lung environment. In the airways, P. aeruginosa undergoes a broad metabolic rewiring as a consequence of the nutritional and stressful complexity of the lungs. However, the role of such metabolic rewiring on the infection outcome is poorly understood. Here, we review the metabolic evolution of clinical strains of P. aeruginosa during a cystic fibrosis lung infection and the metabolic functions operating in vivo under patho-physiological conditions. Finally, we discuss the perspective of modeling the cystic fibrosis environment using genome scale metabolic models of P. aeruginosa. Understanding the physiological changes occurring during the infection may pave the way to a more effective treatment for P. aeruginosa lung infections.

Highlights

  • Pseudomonas aeruginosa is an opportunistic pathogen with high medical importance

  • Even though the specific formulations vary between SCFM2 and Artificial Sputum Medium (ASM), both contain all the fundamental components of the Cystic Fibrosis (CF) mucus, and they represent the gold standards used in many laboratories for investigating P. aeruginosa in a CF context

  • CF airways are complex and highly structured environments, in which Pseudomonas aeruginosa is subjected to steep gradients of nutrients and to stresses of various types, and in which the bacteria optimize over time their physiology in response to the immediate surroundings

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Summary

Introduction

Pseudomonas aeruginosa is an opportunistic pathogen with high medical importance. It is commonly found in natural environments such as soils, plants, and waters but it can cause diseases in plants, animals, and humans [1]. While in healthy people the mucus provides protection against inhaled particles and it is cleared through the mucociliary escalator, its abnormal accumulation in CF patients causes breathing difficulties, persistent coughing and lung inflammation such as bronchitis and infective pneumonia. Over time, this condition leads to reduced lung function which will eventually lead to lung transplantation as a consequence of the progressive respiratory failure. P. aeruginosa has a high capability of adapting according to the changing conditions and the presence of stresses This makes it successful in colonizing the CF airways for long time periods and difficult to treat in the clinics.

Individual Complexity of the CF Mucus
Composition of the CF Sputum
Mimicking the Nutritional Lung-Like Conditions
Heterogeneity of Metabolic Profiles
Amino Acids Auxotrophies
Metabolic Rewiring of Clinical Strains
Mutations on Non-Metabolic Genes Causing Metabolic Changes
Pseudomonas aeruginosa In-Situ Metabolic Program
Metabolic Configuration in the CF Airways
Modelling the CF Dynamics in Silico
Findings
Conclusions
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