Interplay between biofilm microenvironment and pathogenicity of Pseudomonas aeruginosa in cystic fibrosis lung chronic infection

Guillaume, Olivier; Butnarasu, Cosmin; Visentin, Sonja; Reimhult, Erik

doi:10.1016/j.bioflm.2022.100089

Cited by 18 publications

(9 citation statements)

References 137 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with in vivo data in other studies that have found up to 84% of endotracheal tubes extubated from patients were completely covered in confluent biofilm (82), and that this high coverage of biofilm increased the likelihood of ventilator-associated pneumonia (23). The microcolony structures observed in our biofilms are similar to those formed in sputum due to the presence of mucin and DNA (83), and the overall structure of the P. aeruginosa biofilms in our model -punctuated with gaps, giving a lacy or spongy appearance -resembled that seen in a cystic fibrosis lung biofilm model using light microscopy (41,84,85). For LB-grown K. pneumoniae, only small aggregates of biofilm could be found on endotracheal tubes, whilst SVAM resulted in extensive, matrix covered biofilms being observed.…”

Section: Discussionsupporting

confidence: 68%

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia

Walsh,

Parmenter,

Bakker

et al. 2024

Preprint

View full text Add to dashboard Cite

Defined as a pneumonia occurring after more than 48 hours of mechanical ventilation via an endotracheal tube, ventilator-associated pneumonia results from biofilm formation on the indwelling tube, seeding the patient’s lower airways with pathogenic microbes such asPseudomonas aeruginosa, Klebsiella pneumoniae,andCandida albicans.Currently there is a lack of accuratein vitromodels of ventilator-associated pneumonia development. This greatly limits our understanding of how the in-host environment alters pathogen physiology and the efficacy of ventilator-associated pneumonia prevention or treatment strategies. Here, we showcase a reproducible model that simulates biofilm formation of these pathogens in a host-mimicking environment, and demonstrate that the biofilm matrix produced differs from that observed in standard laboratory growth medium. In our model, pathogens are grown on endotracheal tube segments in the presence of a novel synthetic ventilator airway mucus (SVAM) medium that simulates the in-host environment. Matrix-degrading enzymes and cryo-SEM were employed to characterise the system in terms of biofilm matrix composition and structure, as compared to standard laboratory growth medium. As seen in patients, the biofilms of ventilator-associated pneumonia pathogens in our model either required very high concentrations of antimicrobials for eradication, or could not be eradicated. However, combining matrix-degrading enzymes with antimicrobials greatly improved biofilm eradication of all pathogens. Ourin vitroendotracheal tube (IVETT) model informs on fundamental microbiology in the ventilator-associated pneumonia context, and has broad applicability as a screening platform for antibiofilm measures including the use of matrix-degrading enzymes as antimicrobial adjuvants.ImportanceThe incidence of ventilator-associated pneumonia in mechanically ventilated patients is between 5-40%, increasing to 50-80% in patients suffering from coronavirus disease 2019 (COVID-19). The mortality rate of ventilator-associated pneumonia patients can reach 45%. Treatment of the endotracheal tube biofilms that cause ventilator-associated pneumonia is extremely challenging, with causative organisms able to persist in endotracheal tube biofilm despite appropriate antimicrobial treatment in 56% of ventilator-associated pneumonia patients. Flawed antimicrobial susceptibility testing often means that ventilator-associated pneumonia pathogens are insufficiently treated, resulting in patients experiencing ventilator-associated pneumonia recurrence. Here we present anin vitroendotracheal tube biofilm model that recapitulates key aspects of endotracheal tube biofilms, including dense biofilm growth and elevated antimicrobial tolerance. Thus our biofilm model can be used as a ventilated airway simulating environment, aiding the development of anti-ventilator-associated pneumonia therapies and antimicrobial endotracheal tubes that can one day improve the clinical outcomes of mechanically ventilated patients.

show abstract

Section: Discussionsupporting

confidence: 68%

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia

Walsh,

Parmenter,

Bakker

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Accordingly, we assumed CLPM could bind with the biofilm EPS via the cross‐linking between the alginate molecule on the hydrogel shell and the EPS. [ 43 ] To verify the effect of CLPM doping on the mechanical properties of the biofilm, we simulated the elastic modulus of biofilm under external force by 3D finite element method (Figure 4h). When the FAs core of CLPM converted to the liquid phase, the elasticity modulus of adjacent biofilm sharply reduced.…”

Section: Resultsmentioning

confidence: 99%

The Self‐Adaptive Nanosystem for Implant‐Related Infections Theranostics via Phase‐Change Driven Anti‐Biofilm and the Enhancement of Immune Memory

Xiao

Yin

et al. 2023

Adv Funct Materials

View full text Add to dashboard Cite

Implant‐related infections (IRIs), characterized by the formation of bacterial biofilms and immunosuppressive microenvironment, are a common but tricky clinical issue. In this study, a self‐adaptive theranostics nanosystem is designed based on phase change material (PCM) for IRIs therapy, which can monitor the severity of infection in real time and automatically provide the most appropriate treatment on demand. The nanosystem called CaAlg/LOD/POD@MNO/FAs (CLPM) is made of the fatty acids (FAs) core with dissolved minocycline (MNO) and the calcium alginate (CaAlg) shell with an immobilized lactate oxidase/pyruvate oxidase (LOD/POD) enzyme‐linked system. When the level of infection is mild (wound temperature < 39 °C), the CLPMs perform a bacteriostatic function by slowly releasing MNO from the solid‐phase FAs core. When the infection deteriorates (wound temperature > 39 °C), the solid‐to‐liquid phase change of FAs not only enables a rapid release of MNO but also disrupts the mechanical strength of the biofilm skeleton doped with CLPM, performing a bactericidal function. In addition, CLPM can reduce the accumulation of bacteria‐derived lactate to address lactate‐induced immunosuppression and enhance immune memory response, thereby inhibiting infection recurrence.

show abstract

“…Production of biofilm is frequently observed owing to overproduction of exopolysaccharide alginate; this phenomenon also accounts for the conversion from the rough to the mucoid phenotype, posing the bases for the establishment of a chronic infection [43,45 ▪ ]. Such phenotypic switch aid P. aeruginosa in surviving in the lung microenvironment, decreasing bacterial clearance by the host immune system and effectiveness of antimicrobial agents, overall impairing the global host response to infection [46].…”

Section: Text Of Reviewmentioning

confidence: 99%

The microbiology and pathogenesis of nonfermenting Gram-negative infections

Di Pilato,

Willison,

Marchese

2023

Current Opinion in Infectious Diseases

View full text Add to dashboard Cite

Purpose of the review This review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB). Recent findings The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients’ population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged. Summary NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.

show abstract

Interplay between biofilm microenvironment and pathogenicity of Pseudomonas aeruginosa in cystic fibrosis lung chronic infection

Cited by 18 publications

References 137 publications

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia

The Self‐Adaptive Nanosystem for Implant‐Related Infections Theranostics via Phase‐Change Driven Anti‐Biofilm and the Enhancement of Immune Memory

The microbiology and pathogenesis of nonfermenting Gram-negative infections

Contact Info

Product

Resources

About