scholarly journals Pseudomonas aeruginosa Biofilms Exposed to Imipenem Exhibit Changes in Global Gene Expression and β-Lactamase and Alginate Production

2004 ◽  
Vol 48 (4) ◽  
pp. 1175-1187 ◽  
Author(s):  
Niels Bagge ◽  
Martin Schuster ◽  
Morten Hentzer ◽  
Oana Ciofu ◽  
Michael Givskov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Lung Function ◽  
Structural Changes ◽  
Global Gene Expression ◽  
Significant Differential Expression ◽  
Alginate Production ◽  
Impaired Lung Function ◽  
Subinhibitory Concentrations ◽  
Suppressive Antibiotic Therapy

ABSTRACT The lungs of cystic fibrosis (CF) patients are commonly colonized with Pseudomonas aeruginosa biofilms. Chronic endobronchial P. aeruginosa infections are impossible to eradicate with antibiotics, but intensive suppressive antibiotic therapy is essential to maintain the lung function of CF patients. The treatment often includes β-lactam antibiotics. How these antibiotics influence gene expression in the surviving biofilm population of P. aeruginosa is not clear. Thus, we used the microarray technology to study the effects of subinhibitory concentrations of a β-lactam antibiotic, imipenem, on gene expression in biofilm populations. Many genes showed small but statistically significant differential expression in response to imipenem. We identified 34 genes that were induced or repressed in biofilms exposed to imipenem more than fivefold compared to the levels of induction or repression for the controls. As expected, the most strongly induced gene was ampC, which codes for chromosomal β-lactamase. We also found that genes coding for alginate biosynthesis were induced by exposure to imipenem. Alginate production is correlated to the development of impaired lung function, and P. aeruginosa strains isolated from chronically colonized lungs of CF patients are nearly always mucoid due to the overproduction of alginate. Exposure to subinhibitory concentrations of imipenem caused structural changes in the biofilm, e.g., an increased biofilm volume. Increased levels of alginate production may be an unintended adverse consequence of imipenem treatment in CF patients.

scholarly journals Individual Matrix Metalloproteinases Control Distinct Transcriptional Responses in Airway Epithelial Cells Infected with Pseudomonas aeruginosa

2007 ◽  
Vol 75 (12) ◽  
pp. 5640-5650 ◽  
Author(s):  
Sean Y. Kassim ◽  
Sina A. Gharib ◽  
Brigham H. Mecham ◽  
Timothy P. Birkland ◽  
William C. Parks ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Initial Point ◽  
Global Gene Expression ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Transcriptional Responses ◽  
Matrix Metalloproteinase 7 ◽  
Node Network ◽  
Global Gene Expression Analysis

ABSTRACT Airway epithelium is the initial point of host-pathogen interaction in Pseudomonas aeruginosa infection, an important pathogen in cystic fibrosis and nosocomial pneumonia. We used global gene expression analysis to determine airway epithelial transcriptional responses dependent on matrilysin (matrix metalloproteinase 7 [MMP-7]) and stromelysin-2 (MMP-10), two MMPs induced by acute P. aeruginosa pulmonary infection. Extraction of differential gene expression (EDGE) analysis of gene expression changes in P. aeruginosa-infected organotypic tracheal epithelial cell cultures from wild-type, Mmp7 −/−, and Mmp10 −/− mice identified 2,091 matrilysin-dependent and 1,628 stromelysin-2-dependent genes that were differentially expressed. Key node network analysis showed that these MMPs controlled distinct gene expression programs involved in proliferation, cell death, immune responses, and signal transduction, among other host defense processes. Our results demonstrate discrete roles for these MMPs in regulating epithelial responses to Pseudomonas infection and show that a global genomics strategy can be used to assess MMP function.

scholarly journals Global Gene Expression Profiles Suggest an Important Role for Nutrient Acquisition in Early Pathogenesis in a Plant Model of Pseudomonas aeruginosa Infection

2008 ◽  
Vol 74 (18) ◽  
pp. 5784-5791 ◽  
Author(s):  
Tiffany L. Weir ◽  
Valerie J. Stull ◽  
Dayakar Badri ◽  
Lily A. Trunck ◽  
Herbert P. Schweizer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Salicylic Acid ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Defense Responses ◽  
N Gene ◽  
Virulence Determinants ◽  
In Planta

ABSTRACT Although Pseudomonas aeruginosa is an opportunistic pathogen that does not often naturally infect alternate hosts, such as plants, the plant-P. aeruginosa model has become a widely recognized system for identifying new virulence determinants and studying the pathogenesis of the organism. Here, we examine how both host factors and P. aeruginosa PAO1 gene expression are affected in planta after infiltration into incompatible and compatible cultivars of tobacco (Nicotiana tabacum L.). N. tabacum has a resistance gene (N) against tobacco mosaic virus, and although resistance to PAO1 infection is correlated with the presence of a dominant N gene, our data suggest that it is not a factor in resistance against PAO1. We did observe that the resistant tobacco cultivar had higher basal levels of salicylic acid and a stronger salicylic acid response upon infiltration of PAO1. Salicylic acid acts as a signal to activate defense responses in plants, limiting the spread of the pathogen and preventing access to nutrients. It has also been shown to have direct virulence-modulating effects on P. aeruginosa. We also examined host effects on the pathogen by analyzing global gene expression profiles of bacteria removed from the intracellular fluid of the two plant hosts. We discovered that the availability of micronutrients, particularly sulfate and phosphates, is important for in planta pathogenesis and that the amounts of these nutrients made available to the bacteria may in turn have an effect on virulence gene expression. Indeed, there are several reports suggesting that P. aeruginosa virulence is influenced in mammalian hosts by the availability of micronutrients, such as iron and nitrogen, and by levels of O2.

scholarly journals Effect of vfr mutation on global gene expression and catabolite repression control of Pseudomonas aeruginosa

Microbiology ◽  
2002 ◽  
Vol 148 (5) ◽  
pp. 1561-1569 ◽  
Author(s):  
Sang-Jin Suh ◽  
Laura J Runyen-Janecky ◽  
Tricia C Maleniak ◽  
Paul Hager ◽  
Carolyn H MacGregor ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Catabolite Repression ◽  
Global Gene Expression

scholarly journals Involvement of an ATP-Dependent Protease, PA0779/AsrA, in Inducing Heat Shock in Response to Tobramycin in Pseudomonas aeruginosa

2011 ◽  
Vol 55 (5) ◽  
pp. 1874-1882 ◽  
Author(s):  
Kristen N. Kindrachuk ◽  
Lucía Fernández ◽  
Manjeet Bains ◽  
Robert E. W. Hancock
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Heat Shock ◽  
Microarray Analysis ◽  
Prolonged Exposure ◽  
Short Term ◽  
Heat Shock Genes ◽  
Content Type ◽  
Expression Levels ◽  
Subinhibitory Concentrations

ABSTRACTThe adaptive resistance ofPseudomonas aeruginosato aminoglycosides is known to occur during chronic lung infections in cystic fibrosis patients in response to nonlethal concentrations of aminoglycosides. Not only is it difficult to achieve high levels of drug throughout the dehydrated mucus in the lung, but also steep oxygen gradients exist across the mucus layer, further reducing the bactericidal activity of aminoglycosides. In this study, microarray analysis was utilized to examine the gene responses ofP. aeruginosato lethal, inhibitory, and subinhibitory concentrations of tobramycin under aerobic and anaerobic conditions. While prolonged exposure to subinhibitory concentrations of tobramycin caused increased levels of expression predominantly of the efflux pump genesmexXY, the greatest increases in gene expression levels in response to lethal concentrations of tobramycin involved a number of heat shock genes and the PA0779 gene (renamed hereasrA), encoding an alternate Lon protease. Microarray analysis of anasrA::luxCDABEtransposon mutant revealed that the induction of heat shock genes in response to tobramycin in this mutant was significantly decreased compared to that in the parent strain. The level of expression ofasrAwas induced from an arabinose-inducible promoter to 35-fold greater than wild-type expression levels in the absence of tobramycin, and this overexpression alone caused an increased expression of the heat shock genes, as determined by quantitative PCR (qPCR). This overexpression ofasrAconferred short-term protection against lethal levels (4 μg/ml) of tobramycin but did not affect the tobramycin MIC. The RpoH heat shock sigma factor was found to be involved in the regulation ofasrAin response to both heat shock and tobramycin at the posttranscriptional level. The results of this work suggest that the tobramycin concentration has a significant impact on the gene expression ofP. aeruginosa, with lethal concentrations resulting in immediate adaptations conferring short-term protection, such as the induction of the heat shock response, and with subinhibitory concentrations leading to more sustainable long-term protection mechanisms, such as increased efflux.

scholarly journals Reduced neutrophil elastase inhibitor elafin and elevated TGFβ1 are linked to inflammatory response in sputum of CF patients with Pseudomonas aeruginosa

2021 ◽  
pp. 00636-2020
Author(s):  
Jan C. Thomassen ◽  
Tobias Trojan ◽  
Maxine Walz ◽  
Christina Vohlen ◽  
Gregor Fink ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Neutrophil Elastase ◽  
Research Question ◽  
Neutrophil Elastase Inhibitor ◽  
Elastase Inhibitor ◽  
Impaired Lung Function ◽  
Minimum Age ◽  
The Impact ◽  
Signaling Components

Research questionPulmonary disease progression in patients with cystic fibrosis (CF) is characterized by inflammation and fibrosis, and aggravated by Pseudomonas aeruginosa (Pa). We investigated the impact of Pa specifically 1) on protease/antiprotease balance and 2) inflammation, as well as 3) the link of both parameters to clinical parameters of CF-patients.MethodsTGFβ1, IL1β, IL8, neutrophil elastase (NE) and elastase inhibitor elafin were measured (ELISA assays), and gene expression of the NF-ĸB pathway was assessed (RT-PCR) in the sputum of 60 CF-patients with a minimum age of 5 years. Spirometry was assessed according to ATS guidelines.Results1) NE was markedly increased in Pa-positive sputum, whereas elafin was significantly decreased. 2) Increased IL1β/IL8 were associated with both Pa infection and reduced FEV1, as well as sputum TGFβ1 was elevated in Pa-infected CF-patients and linked to an impaired lung function. 3) Moreover, gene expression of NF-ĸB signaling components was increased in sputum of Pa-infected patients; these findings were positively correlated with IL8.ConclusionOur study links Pa infection to an imbalance of NE and NE-inhibitor elafin and increased inflammatory mediators. Moreover, our data demonstrate an association between high TGFβ1 sputum levels and a progress in chronic lung inflammation and pulmonary fibrosis in CF. Controlling the excessive airway inflammation by inhibition of NE and TGFβ1 might be promising therapeutic strategies in future CF therapy and a possible complement to CFTR-modulators.

scholarly journals Update on pharmacotherapy for adult bronchiectasis

2020 ◽  
Vol 63 (8) ◽  
pp. 486-492
Author(s):  
Hayoung Choi ◽  
Hyun Lee ◽  
Seung Won Ra ◽  
Yeon-Mok Oh
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Lung Function ◽  
Risk Of Infection ◽  
Mucus Clearance ◽  
Airway Clearance ◽  
Increased Risk ◽  
Impaired Lung Function ◽  
Anti Inflammatory

Bronchiectasis refers to abnormal dilatation of the bronchi, which leads to the failure of mucus clearance and increased risk of infection. Pharmacotherapy for stable bronchiectasis includes oral or inhaled mucoactive agents, anti-inflammatory therapy, inhaled bronchodilators, long-term antibiotics, and long-term macrolide treatment. Among them, mucoactive agents are the most common adjunctive agents to airway clearance techniques. When patients with impaired lung function suffer from dyspnea, inhaled bronchodilators may be prescribed to relieve the symptom. Long-term macrolide treatment has been proven to prevent exacerbation in patients with frequent bronchiectasis exacerbation. If exacerbation occurs despite the above mentioned treatments, one or two weeks of antibiotics should be prescribed to cover respiratory bacteria that include <i>Pseudomonas aeruginosa</i>. Because evidence supporting the use of pharmacotherapy for bronchiectasis is weak, further research is warranted.

scholarly journals PvrA is a novel regulator that contributes to Pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids

2020 ◽  
Vol 48 (11) ◽  
pp. 5967-5985
Author(s):  
Xiaolei Pan ◽  
Zheng Fan ◽  
Lei Chen ◽  
Chang Liu ◽  
Fang Bai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Fatty Acid ◽  
Coenzyme A ◽  
Regulatory Gene ◽  
Global Gene Expression ◽  
Bacterial Virulence ◽  
Regulatory Genes ◽  
Bacterial Utilization ◽  
Target Promoters

Abstract During infection of a host, Pseudomonas aeruginosa orchestrates global gene expression to adapt to the host environment and counter the immune attacks. P. aeruginosa harbours hundreds of regulatory genes that play essential roles in controlling gene expression. However, their contributions to the bacterial pathogenesis remain largely unknown. In this study, we analysed the transcriptomic profile of P. aeruginosa cells isolated from lungs of infected mice and examined the roles of upregulated regulatory genes in bacterial virulence. Mutation of a novel regulatory gene pvrA (PA2957) attenuated the bacterial virulence in an acute pneumonia model. Chromatin immunoprecipitation (ChIP)-Seq and genetic analyses revealed that PvrA directly regulates genes involved in phosphatidylcholine utilization and fatty acid catabolism. Mutation of the pvrA resulted in defective bacterial growth when phosphatidylcholine or palmitic acid was used as the sole carbon source. We further demonstrated that palmitoyl coenzyme A is a ligand for the PvrA, enhancing the binding affinity of PvrA to its target promoters. An arginine residue at position 136 was found to be essential for PvrA to bind palmitoyl coenzyme A. Overall, our results revealed a novel regulatory pathway that controls genes involved in phosphatidylcholine and fatty acid utilization and contributes to the bacterial virulence.

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