scholarly journals Pseudomonas aeruginosa Elastase Contributes to the Establishment of Chronic Lung Colonization and Modulates the Immune Response in a Murine Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Cristina Cigana ◽  
Jérôme Castandet ◽  
Nicolas Sprynski ◽  
Medede Melessike ◽  
Lilha Beyria ◽  
...  

Chronic infection by Pseudomonas aeruginosa in cystic fibrosis (CF) patients is a major contributor to progressive lung damage and is poorly treated by available antibiotic therapy. An alternative approach to the development of additional antibiotic treatments is to identify complementary therapies which target bacterial virulence factors necessary for the establishment and/or maintenance of the chronic infection. The P. aeruginosa elastase (LasB) has been suggested as an attractive anti-virulence target due to its extracellular location, its harmful degradative effects on host tissues and the immune system, and the potential to inhibit its activity using small molecule inhibitors. However, while the relevance of LasB in acute P. aeruginosa infection has been demonstrated, it is still unclear whether this elastase might also play a role in the early phase of chronic lung colonization. By analyzing clinical P. aeruginosa clonal isolates from a CF patient, we found that the isolate RP45, collected in the early phase of persistence, produces large amounts of active LasB, while its clonal variant RP73, collected after years of colonization, does not produce it. When a mouse model of persistent pneumonia was used, deletion of the lasB gene in RP45 resulted in a significant reduction in mean bacterial numbers and incidence of chronic lung colonization at Day 7 post-challenge compared to those mice infected with wild-type (wt) RP45. Furthermore, deletion of lasB in strain RP45 also resulted in an increase in immunomodulators associated with innate and adaptive immune responses in infected animals. In contrast, deletion of the lasB gene in RP73 did not affect the establishment of chronic infection. Overall, these results indicate that LasB contributes to the adaptation of P. aeruginosa to a persistent lifestyle. In addition, these findings support pharmacological inhibition of LasB as a potentially useful therapeutic intervention for P. aeruginosa-infected CF patients prior to the establishment of a chronic infection.

2013 ◽  
Vol 95 (12) ◽  
pp. 1548-1553 ◽  
Author(s):  
Domenic Vital ◽  
David Holzmann ◽  
Annette Boehler ◽  
Markus Hofer

1965 ◽  
Vol 240 (8) ◽  
pp. 3295-3304
Author(s):  
Kazuyuki Morihara ◽  
Hiroshige Tsuzuki ◽  
Tatsushi Oka ◽  
Hideo Inoue ◽  
Mitsuo Ebata

1989 ◽  
Vol 57 (12) ◽  
pp. 3783-3787 ◽  
Author(s):  
P A Bejarano ◽  
J P Langeveld ◽  
B G Hudson ◽  
M E Noelken

2021 ◽  
Vol 42 (04) ◽  
pp. 587-594
Author(s):  
Laia Fernández-Barat ◽  
Victoria Alcaraz-Serrano ◽  
Rosanel Amaro ◽  
Antoni Torres

Abstract Pseudomonas aeruginosa (PA) in patients with bronchiectasis (BE) is associated with a poor outcome and quality of life, and its presence is considered a marker of disease severity. This opportunistic pathogen is known for its ability to produce biofilms on biotic or abiotic surfaces and to survive environmental stress exerted by antimicrobials, inflammation, and nutrient or oxygen depletion. The presence of PA biofilms has been linked to chronic respiratory infection in cystic fibrosis but not in BE. There is considerable inconsistency in the reported infection/eradication rates of PA and chronic PA. In addition, inadequate antimicrobial treatment may potentiate the progression from intermittent to chronic infection and also the emergence of antibiotic resistance. A better comprehension of the pathophysiology of PA infections and its implications for BE is urgently needed. This can drive improvements in diagnostic accuracy, can move us toward a new consensus definition of chronic infection, can better define the follow-up of patients at risk of PA, and can achieve more successful eradication rates. In addition, the new technological advances regarding molecular diagnostics, -omics, and biomarkers require us to reconsider our traditional concepts.


Sign in / Sign up

Export Citation Format

Share Document