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Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung
Published on: January 22, 2021
[Acute bacterial exacerbation of chronic obstructive pulmonary disease and biofilm]
1Istituto di Malattie Respiratorie, Universita di Milano, U.O.C. Pneumologia, Ospedale L. Sacco, Milano.
Abstract:
The lower respiratory tract of patients affected by COPD is constantly colonized by pathogenic microrganisms such as H. influenzae, M. catarrhalis and S. pneumoniae. Role of bacterial colonization of big and small airways in patients affected by COPD is still unclear but it is likely to play a role in directly or indirectly maintaining the vicious circle of infection/inflammation. Colonizer pathogens are capable to stimulate mucus production, to alter the ciliary function by inducing dyskinesia and stasis; in addition, they represent a strong stimulus for neutrophils to come in the airways, which release elastase that, in turn, inhibit the mucus-ciliary function. The same pathogens are responsible for epithelial damage and chronic inflammation, by releasing neutrophilic elastase, leading to the damage progression and obstruction. Recent studies have also shown that infection sustained by H. influenzae is not limited to bronchial mucosa, i.e. surface epithelial cells, but that the pathogen is capable to penetrate cells, so spreading the infection in sub-epithelial cellular layers. In addition, the ability to produce biofilm is another possible defence mechanism which allows them to grow and colonise. Such a mechanism could in part explain the lack of response to antimicrobials and contribute to stimulation of parenchymal inflammatory response, the cause of pathological-anatomic damage which occurs in COPD. The impossibility to eradicate chronic infection and bacterial exacerbations of COPD are likely the elements that promt and worsen obstruction, so determining the disease's progression.
Insights
Pathogenic bacteria like Haemophilus influenzae colonize airways in chronic obstructive pulmonary disease (COPD), driving inflammation and obstruction. Biofilm formation and intracellular invasion by these microbes contribute to persistent infections and disease progression.
Area of Science:
- Pulmonary Medicine
- Microbiology
- Immunology
Background:
- The lower respiratory tract in chronic obstructive pulmonary disease (COPD) is frequently colonized by pathogens such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae.
- The precise role of this bacterial colonization in COPD pathogenesis, particularly in the vicious cycle of infection and inflammation, remains incompletely understood.
Purpose of the Study:
- To elucidate the mechanisms by which bacterial colonization contributes to the progression of chronic obstructive pulmonary disease (COPD).
- To explore the role of specific bacterial virulence factors, including biofilm formation and intracellular invasion, in COPD exacerbations and inflammation.
Main Methods:
- Review of existing literature on bacterial colonization in COPD.
- Analysis of the impact of bacterial pathogens on airway mucus production, ciliary function, and neutrophil recruitment.
- Examination of bacterial strategies like biofilm formation and intracellular invasion in the context of COPD.
Main Results:
- Colonizing pathogens stimulate mucus hypersecretion and impair ciliary function, while also promoting neutrophil elastase release, which further compromises airway clearance.
- Haemophilus influenzae demonstrates the ability to invade bronchial epithelial cells, extending infection beyond the mucosal surface.
- Biofilm production by these bacteria may confer resistance to antimicrobials and promote inflammation, contributing to lung damage and obstruction.
Conclusions:
- Bacterial colonization is a significant factor in COPD, perpetuating inflammation and airway obstruction through various virulence mechanisms.
- The inability to eradicate chronic infections and frequent bacterial exacerbations are key drivers of COPD progression.
- Understanding these bacterial contributions is crucial for developing targeted therapeutic strategies to manage COPD effectively.
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