Targeting mechanisms of Pseudomonas aeruginosa pathogenesis

Kipnis, Éric; Sawa, Teiji; Wiener-Kronish, Jeanine P.

doi:10.1016/j.medmal.2005.10.007

Cited by 273 publications

(249 citation statements)

References 166 publications

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“…P. aeruginosa exogenous proteases such as AprA and LasB can alter mucociliary clearance, degrade lung tissue and dysregulate host immune system, thus strongly contributing to lung disease [6]. We previously showed that P. aeruginosa proteases are major exoproducts of selected clinical strains and that they might interfere with the host immune system by down-regulating CXCR1 on the surface of human neutrophils [41].…”

Section: Discussionmentioning

confidence: 99%

“…Among these, proteases can disrupt lung tissue and modulate host inflammatory response [6–8]; the blue-green pigment pyocyanin causes host cells oxidative stress and dysregulates immune mechanisms [9–11]; the siderophore pyoverdine is both able to sequester iron from host depots and to regulate bacterial virulence [12,13]. In a previous study, we observed that macrolide antibiotic azithromycin (AZM) acts on P. aeruginosa by reducing the synthesis of proteases and other exoproducts involved in bacterial virulence and the associated host inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

et al. 2018

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Background: Cystic fibrosis (CF) lung infection is a complex condition where opportunistic pathogens and defective immune system cooperate in developing a constant cycle of infection and inflammation. The major pathogen, Pseudomonas aeruginosa, secretes a multitude of virulence factors involved in host immune response and lung tissue damage. In this study, we examined the possible anti-inflammatory effects of molecules inhibiting P. aeruginosa virulence factors.Methods: Pyocyanin, pyoverdine and proteases were measured in bacterial culture supernatant from different P. aeruginosa strains. Inhibition of virulence factors by sub-inhibitory concentrations of clarithromycin and by protease inhibitors was evaluated. Lung inflammatory response was monitored by in vivo bioluminescence imaging in wild-type and CFTR-knockout mice expressing a luciferase gene under the control of a bovine IL-8 promoter.Results: The amount of proteases, pyocyanin and pyoverdine secreted by P. aeruginosa strains was reduced after growth in the presence of a sub-inhibitory dose of clarithromycin. Intratracheal challenge with culture supernatant containing bacteria-released products induced a strong IL-8-mediated response in mouse lungs while lack of virulence factors corresponded to a reduction in bioluminescence emission. Particularly, sole inactivation of proteases by inhibitors Ilomastat and Marimastat also resulted in decreased lung inflammation.Conclusions: Our data support the assumption that virulence factors are involved in P. aeruginosa pro-inflammatory action in CF lungs; particularly, proteases seem to play an important role. Inhibition of virulence factors production and activity resulted in decreased lung inflammation; thus, clarithromycin and protease inhibitors potentially represent additional therapeutic therapies for P. aeruginosa-infected patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

et al. 2018

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“…Indeed, P. aeruginosa is the most common cause of acute nosocomial pneumonia, and of chronic respiratory infections in cystic fibrosis patients. P. aeruginosa infections are characterized by their high incidence, severity, and increasing high-level resistance to antibiotics (Kipnis et al, 2006). While the human lung inhales more than 10 000 litres of non-sterile air each day, the lower airway remains infection-free and maintains no commensal microbial population (Flato et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

The sensor kinase PhoQ mediates virulence in Pseudomonas aeruginosa

et al. 2009

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Pseudomonas aeruginosa is a ubiquitous environmental Gram-negative bacterium that is also a major opportunistic human pathogen in nosocomial infections and cystic fibrosis chronic lung infections. PhoP-PhoQ is a two-component regulatory system that has been identified as essential for virulence and cationic antimicrobial peptide resistance in several other Gram-negative bacteria. This study demonstrated that mutation of phoQ caused reduced twitching motility, biofilm formation and rapid attachment to surfaces, 2.2-fold reduced cytotoxicity to human lung epithelial cells, substantially reduced lettuce leaf virulence, and a major, 10 000-fold reduction in competitiveness in chronic rat lung infections. Microarray analysis revealed that PhoQ controlled the expression of many genes consistent with these phenotypes and with its known role in polymyxin B resistance. It was also demonstrated that PhoQ controls the expression of many genes outside the known PhoP regulon.

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“…There is also an increasing number of cases of neonatal infections caused by Pseudomonas aeruginosa, opportunistic Gram negative bacilli with resistance to many antibiotics, especially among hospitalized newborns in the intensive care units (6,11,12). These microorganisms are found in various environments, including damp reservoirs of any hospital and even in disinfectant solutions.…”

Section: Introductionmentioning

confidence: 99%

Prevalence and Sensitivity of Bacilli and Pseudomonas in the Newborn’s Oral Cavity

et al. 2017

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The aim of this study was to isolate Enterobacteria and Pseudomonas from the oral cavity of hospitalized newborns (NB) and determine their prevalence and the sensitivity profile to most commonly used antibiotics for this age group. Samples from the oral cavity of NB from 24 to 48 h age were collected using swabs. The samples were inoculated on MacConkey agar, incubated and the colonies counted and identified. For each strain, the minimum inhibitory concentration (MIC) was determined using agar dilution test. Tests for enterobacteria producing extended spectrumβ-lactamases (ESBL) were performed using agar diffusion. Descriptive statistics was used for data analysis. Two of the isolated strains were submitted to the susceptibility test in biofilm. Of the collected samples, 8% presented Enterobacteria (mean of 6,141 CFU/mL) and no Pseudomona species was isolated. Positive samples were from NB in accommodation set or in the NB nursery. Enterobacter was the most prevalent genus and some strains were resistant to ampicillin, gentamicin and cephalothin. No ESBL strain was detected. Microorganisms in biofilms were resistant to all antibiotics, with concentrations four times higher than MIC. The presence of enterobacteria in the oral cavity of newborns, especially some strains resistant to normally used antibiotics, warns to the need for care to avoid the early colonization of this niche and the occurrence of a possible hospital infection in this age group.P r e v a l e n c e a n d S e n s i t i v i t y o f B a c i l l i a n d P s e u d o m o n a s i n t h e N e w b o r n ' s O r a l C a v i t y

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Targeting mechanisms of Pseudomonas aeruginosa pathogenesis

Cited by 273 publications

References 166 publications

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

The sensor kinase PhoQ mediates virulence in Pseudomonas aeruginosa

Prevalence and Sensitivity of Bacilli and Pseudomonas in the Newborn’s Oral Cavity

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