Evolution of Pseudomonas aeruginosa virulence in infected patients revealed in a Dictyostelium discoideum host model
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Published on: December 20, 2018
E Lelong1, A Marchetti, M Simon
1Department of Cell Physiology and Metabolism, Centre Médical Universitaire, Geneva Faculty of Medicine, Geneva, Switzerland.
Abstract:
Pseudomonas aeruginosa can cause acute lung infections in intubated patients or chronic infections in patients with cystic fibrosis (CF). In both situations, P. aeruginosa accumulates specific mutations, in particular in the lasR quorum-sensing regulator gene. Using a Dictyostelium discoideum amoeba model, we assessed whether these mutations affect bacterial virulence. Among a collection of clinical isolates from 16 CF patients, initial isolates were fully virulent in 15 patients, but for late isolates collected several years later, virulence was decreased in eight patients. No significant correlation between genetic inactivation of lasR and decreased virulence was observed. Among strains isolated from ten colonized intubated patients, all initial isolates were fully virulent. Despite the accumulation of lasR-inactivating mutations in strains collected over a 3-week period, no decrease in virulence was observed in eight of 10 patients. In one intubated patient, the virulent initial strain was replaced a few days later with a different, less virulent, strain. We observed a gradual decrease in bacterial virulence in only one intubated patient. We conclude that adaptation of P. aeruginosa to chronically infected CF patients can lead to a slow and gradual loss of virulence, as measured in a Dictyostelium model system. However, loss of virulence is not caused predominantly by mutations in lasR. During short-term colonization of intubated patients for up to 20 days, a decrease in virulence was exceptional, despite the accumulation of lasR mutations.
Insights
Pseudomonas aeruginosa adaptation to chronic cystic fibrosis (CF) infections can slowly reduce virulence. However, mutations in the lasR gene are not the primary cause of this decreased virulence in CF patients or during short-term intubated infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Pseudomonas aeruginosa is a significant pathogen causing acute lung infections in intubated patients and chronic infections in cystic fibrosis (CF) patients.
- During chronic infections, P. aeruginosa often accumulates mutations, particularly in the lasR quorum-sensing regulator gene.
Purpose of the Study:
- To investigate the impact of P. aeruginosa mutations, specifically in the lasR gene, on bacterial virulence in both CF and intubated patient models.
- To assess the correlation between lasR gene inactivation and decreased virulence in clinical isolates from different patient populations.
Main Methods:
- Utilized a Dictyostelium discoideum amoeba model to assess bacterial virulence.
- Analyzed clinical isolates from 16 cystic fibrosis patients and 10 intubated patients, examining initial and late isolates for virulence and lasR mutations.
- Compared virulence and lasR mutation accumulation over time in both patient groups.
Main Results:
- In cystic fibrosis patients, late isolates showed decreased virulence in 8 out of 16 patients, with no significant correlation to lasR inactivation.
- In intubated patients, initial isolates were fully virulent, and despite lasR mutations, virulence remained high in most cases over a 3-week period.
- A decrease in virulence was exceptional in intubated patients, with one case of strain replacement by a less virulent variant observed.
Conclusions:
- Adaptation to chronic cystic fibrosis infections can lead to a gradual loss of P. aeruginosa virulence, but lasR mutations are not the predominant cause.
- Short-term colonization of intubated patients rarely results in decreased virulence, even with lasR mutations.
- The lasR gene is not the primary driver of virulence loss in P. aeruginosa during adaptation to different host environments.
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