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 ◽  
...  
2007 ◽  
Vol 75 (12) ◽  
pp. 5640-5650 ◽  
Author(s):  
Sean Y. Kassim ◽  
Sina A. Gharib ◽  
Brigham H. Mecham ◽  
Timothy P. Birkland ◽  
William C. Parks ◽  
...  

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.


2004 ◽  
Vol 48 (4) ◽  
pp. 1175-1187 ◽  
Author(s):  
Niels Bagge ◽  
Martin Schuster ◽  
Morten Hentzer ◽  
Oana Ciofu ◽  
Michael Givskov ◽  
...  

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.


2008 ◽  
Vol 74 (18) ◽  
pp. 5784-5791 ◽  
Author(s):  
Tiffany L. Weir ◽  
Valerie J. Stull ◽  
Dayakar Badri ◽  
Lily A. Trunck ◽  
Herbert P. Schweizer ◽  
...  

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.


2016 ◽  
Vol 82 (22) ◽  
pp. 6715-6727 ◽  
Author(s):  
Jeffrey Meisner ◽  
Joanna B. Goldberg

ABSTRACTThearaC-ParaBADinducible promoter system is tightly controlled and allows gene expression to be modulated over a wide range inEscherichia coli, which has led to its widespread use in other bacteria. Although anecdotal evidence suggests thataraC-ParaBADis leaky inPseudomonas aeruginosa, neither a thorough analysis of this inducible promoter system inP. aeruginosanor a concerted effort to identify alternatives with improved functionality has been reported. Here, we evaluated the functionality of thearaC-ParaBADsystem inP. aeruginosa. Using transcriptional fusions to alacZreporter gene, we determined that the noninduced expression fromaraC-ParaBADis high and cannot be reduced by carbon catabolite repression as it can inE. coli. Modulating translational initiation by altering ribosome-binding site strength reduced the noninduced activity but also decreased the maximal induced activity and narrowed the induction range. Integrating the inducible promoter system into the posttranscriptional regulatory network that controls catabolite repression inP. aeruginosasignificantly decreased the noninduced activity and increased the induction range. In addition to these improvements in the functionality of thearaC-ParaBADsystem, we found that thelacIq-PtacandrhaSR-PrhaBADinducible promoter systems had significantly lower noninduced expression and were inducible over a broader range thanaraC-ParaBAD. We demonstrated that noninduced expression from thearaC-ParaBADsystem supported the function of genes involved in antibiotic resistance and tryptophan biosynthesis inP. aeruginosa, problems that were avoided withrhaSR-PrhaBAD. rhaSR-PrhaBADis tightly controlled, allows gene expression over a wide range, and represents a significant improvement overaraC-ParaBADinP. aeruginosa.IMPORTANCEWe report the shortcomings of the commonly usedEscherichia coli araC-ParaBADinducible promoter system inPseudomonas aeruginosa, successfully reengineered it to improve its functionality, and show that theE. colirhaSR-PrhaBADsystem is tightly controlled and allows inducible gene expression over a wide range inP. aeruginosa.


2020 ◽  
Vol 48 (11) ◽  
pp. 5967-5985
Author(s):  
Xiaolei Pan ◽  
Zheng Fan ◽  
Lei Chen ◽  
Chang Liu ◽  
Fang Bai ◽  
...  

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.


Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.


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