scholarly journals Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Laura C. McCaughey ◽  
Neil. D. Ritchie ◽  
Gillian R. Douce ◽  
Thomas J. Evans ◽  
Daniel Walker
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Murine Model ◽  
Lung Infection ◽  
Specific Protein ◽  
Species Specific

Antibacterial efficacy of R-type pyocins against Pseudomonas aeruginosa on biofilms and in a murine model of acute lung infection

2020 ◽  
Author(s):  
Mar Redero ◽  
Javier Aznar ◽  
Ana I Prieto
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Risk ◽  
Murine Model ◽  
Biofilm Formation ◽  
Bacterial Load ◽  
Preventive Treatment ◽  
Lung Infection ◽  
Before And After ◽  
Treatment Alternatives ◽  
Potential Use

Abstract Background The appearance of MDR strains and the development of biofilms make Pseudomonas aeruginosa infections a therapeutic challenge. To overcome this scenario, bacteriocins have been proposed as a potential adjuvant or alternative to antibiotic treatment. Objectives To study the activity of R-pyocins on biofilms and in a murine model of pneumonia using a high-risk clone of P. aeruginosa. Methods The activity of R-pyocins on P. aeruginosa biofilms was tested on bacteria attached to a silicone surface, before and after biofilm formation. The effectiveness of R1-pyocin was studied in a murine model of pneumonia using ST175, a high-risk clone of P. aeruginosa. Results R-pyocins attacked adherent bacteria, preventing biofilm formation, and penetrated into the biofilm, killing P. aeruginosa within it, resulting in a dramatic reduction in bacterial load. R1-pyocin was active in a murine model of P. aeruginosa lung infection, administered before infection as a preventive treatment, and in acute pneumonia, with efficiency higher than standard colistin treatment. In addition, this work is the first to describe histopathological lung changes after administration of R-pyocins, contributing to the resolution of P. aeruginosa pneumonia in a murine model. Conclusions This work highlights the potential use of the R-pyocins as therapeutic agents, alone or as adjuvants, due to its effectiveness on biofilms and in a murine model of pneumonia using ST175, a high-risk clone of P. aeruginosa. It may thus be feasible to consider R-pyocins as a possible therapeutic alternative in XDR infections, where treatment alternatives are limited.

scholarly journals Anti-Inflammatory Effects of RTD-1 in a Murine Model of Chronic Pseudomonas aeruginosa Lung Infection: Inhibition of NF-κB, Inflammasome Gene Expression, and Pro-IL-1β Biosynthesis

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1043
Author(s):  
Mansour A. Dughbaj ◽  
Jordanna G. Jayne ◽  
A Young J. Park ◽  
Timothy J. Bensman ◽  
Marquerita Algorri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Microarray Analysis ◽  
Lung Tissue ◽  
Murine Model ◽  
Lung Infection ◽  
Cell Counts ◽  
Tissue Homogenates ◽  
Anti Inflammatory

Vicious cycles of chronic airway obstruction, lung infections with Pseudomonas aeruginosa, and neutrophil-dominated inflammation contribute to morbidity and mortality in cystic fibrosis (CF) patients. Rhesus theta defensin-1 (RTD-1) is an antimicrobial macrocyclic peptide with immunomodulatory properties. Our objective was to investigate the anti-inflammatory effect of RTD-1 in a murine model of chronic P. aeruginosa lung infection. Mice received nebulized RTD-1 daily for 6 days. Bacterial burden, leukocyte counts, and cytokine concentrations were evaluated. Microarray analysis was performed on bronchoalveolar lavage fluid (BALF) cells and lung tissue homogenates. In vitro effects of RTD-1 in THP-1 cells were assessed using quantitative reverse transcription PCR, enzyme-linked immunosorbent assays, immunoblots, confocal microscopy, enzymatic activity assays, and NF-κB-reporter assays. RTD-1 significantly reduced lung white blood cell counts on days 3 (−54.95%; p = 0.0003) and 7 (−31.71%; p = 0.0097). Microarray analysis of lung tissue homogenates and BALF cells revealed that RTD-1 significantly reduced proinflammatory gene expression, particularly inflammasome-related genes (nod-like receptor protein 3, Mediterranean fever gene, interleukin (IL)-1α, and IL-1β) relative to the control. In vitro studies demonstrated NF–κB activation was reduced two-fold (p ≤ 0.0001) by RTD-1 treatment. Immunoblots revealed that RTD-1 treatment inhibited proIL-1β biosynthesis. Additionally, RTD-1 treatment was associated with a reduction in caspase-1 activation (FC = −1.79; p = 0.0052). RTD-1 exhibited potent anti-inflammatory activity in chronically infected mice. Importantly, RTD-1 inhibits inflammasome activity, which is possibly a downstream effect of NF-κB modulation. These findings support that this immunomodulatory peptide may be a promising therapeutic for CF-associated lung disease.

scholarly journals Pseudomonas aeruginosa Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid Signaling

2019 ◽  
Vol 10 ◽  
Author(s):  
Eric Morello ◽  
Teresa Pérez-Berezo ◽  
Chloé Boisseau ◽  
Thomas Baranek ◽  
Antoine Guillon ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Lung Infection ◽  
Lipid Signaling

scholarly journals Efficacy of SCH27899 in an Animal Model of Legionnaires' Disease Using Immunocompromised A/J Mice

2000 ◽  
Vol 44 (5) ◽  
pp. 1333-1336 ◽  
Author(s):  
Joan K. Brieland ◽  
David Loebenberg ◽  
Fred Menzel ◽  
Roberta S. Hare
Keyword(s):  
Animal Model ◽  
Murine Model ◽  
Legionella Pneumophila ◽  
Immunocompromised Host ◽  
Lung Infection ◽  
Cortisone Acetate ◽  
Contrast Administration ◽  
Once Daily ◽  
Legionnaires Disease ◽  
Lung Infections

ABSTRACT The efficacy of SCH27899, a new everninomicin antibiotic, against replicative Legionella pneumophila lung infections in an immunocompromised host was evaluated using a murine model of Legionnaires' disease. A/J mice were immunocompromised with cortisone acetate and inoculated intratracheally with L. pneumophilaserogroup 1 (105 CFU per mouse). At 24 h postinoculation, mice were administered either SCH27899 (6 to 60 mg/kg [MPK] intravenously) or a placebo once daily for 5 days, and mortality and intrapulmonary growth of L. pneumophila were assessed. In the absence of SCH27899, there was 100% mortality inL. pneumophila-infected mice, with exponential intrapulmonary growth of the bacteria. In contrast, administration of SCH27899 at a dose of ≥30 MPK resulted in ≥90% survival of infected mice, which was associated with inhibition of intrapulmonary growth ofL. pneumophila. In subsequent studies, the efficacy of SCH27899 was compared to ofloxacin (OFX) and azithromycin (AZI). Administration of SCH27899, OFX, or AZI at a dose of ≥30 MPK once daily for 5 days resulted in ≥85% survival of infected mice and inhibition of intrapulmonary growth of the bacteria. However, L. pneumophila CFU were recovered in lung homogenates following cessation of therapy with all three antibiotics. These studies demonstrate that SCH27899 effectively prevents fatal replicativeL. pneumophila lung infection in immunocompromised A/J mice by inhibition of intrapulmonary growth of the bacteria. However, in this murine model of pulmonary legionellosis, SCH27899, like OFX and AZI, was bacteriostatic.

Assessment of elastase as a Pseudomonas aeruginosa virulence factor in experimental lung infection in mink

1987 ◽  
Vol 13 (3) ◽  
pp. 281-289 ◽  
Author(s):  
Laila Elsadig Elsheikh ◽  
Tony Kronevi ◽  
Bengt Wretlind ◽  
Saleem Abaas ◽  
Barbara H. Iglewski
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factor ◽  
Lung Infection
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