Pf4 infection alters P. aeruginosa virulence
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ABSTRACT:
PROVIDER: PRJNA832798 | ENA |
REPOSITORIES: ENA
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Project description:Pf4 is a filamentous bacteriophage integrated as a prophage into the genome of Pseudomonas aeruginosa PAO1. Pf4 virions can be produced without killing P. aeruginosa. Cell lysis can however occur during superinfection when Pf virions successfully infect a host lysogenized by a Pf superinfective variant. We have previously shown that infection of P. aeruginosa PAO1 with a superinfective Pf4 variant led to abolish twitching motility and to alter biofilm’s architecture. More precisely, the cells embedded into the biofilm were showing for most of them a filamentous morphology, that could be related to the activation of the cell envelope stress response involving both the AlgU and SigX extra cytoplasmic function sigma factors. Herein, we show that Pf4 variant-infection resulted also into a drastic dysregulation of 3,360 genes representing about 58% of P. aeruginosa’s genome, of which about 43% of the virulence factors encoding genes showing a down-regulation. Accordingly, Pf4 variant infection (termed Pf4*) causes in vivo reduction of P. aeruginosa virulence, decreased production of N-acyl-homoserine lactones and 2-alkyl-4-quinolones quorum sensing molecules, and related virulence factors, such as pyocyanin, elastase, and pyoverdine. In addition to virulence encoding genes, expression of genes involved in metabolism, including energy generation and iron homeostasis, was affected, suggesting further relationships between virulence and central metabolism. Altogether, these data suggest that Pf4 phage variant infection results in complex networks dysregulations, leading to reducing acute virulence in P. aeruginosa. This work contributes to the comprehension of the bacterial response to filamentous phage infection.
2022-07-05 | GSE201738 | GEO
Project description:It has been shown that the filamentous phage, Pf4, plays an important role in biofilm development, stress tolerance, genetic variant formation and virulence in Pseudomonas aeruginosa PAO1. These behaviours are linked to the appearance of superinfective phage variants. Here, we have investigated the molecular mechanism of superinfection as well as how the Pf4 phage can control host gene expression to modulate host behaviours. Pf4 exists as a prophage in PAO1 and encodes a homolog of the P2 phage repressor C. Through a combination of molecular techniques, ChIPseq and transcriptomic analyses, we show that repressor C (Pf4r) is the minimal factor for immunity against reinfection by Pf4 possibly through Pf4r binding to its putative promoter region, and that Pf4r also functions as a transcriptional regulator for expression of host genes. A binding motif for Pf4r was also identified. In wild type P. aeruginosa and Pfr4 complemented Pf4 deficient mutant strains, virulence factor related genes including phenazine and type VI secretion system effectors were upregulated, potentially explaining the reduced virulence of Pf4-deficient P. aeruginosa PAO1. X-ray crystal structure analysis shows that Pf4r forms symmetric homo-dimers homologous to the E.coli bacteriophage P2 RepC protein. A mutation associated with the superinfective Pf4r variant, found at the dimer interface, suggests dimer formation may be disrupted, which derepresses phage replication. This is supported by MALS analysis where the Pf4r* protein only shows monomer formation. Collectively, these data suggest the mechanism by which filamentous phages play such an important role in P. aeruginosa biofilm development.
2021-01-31 | GSE154459 | GEO
Project description:Pseudomonas aeruginosa airway infection is the primary cause of death in Cystic Fibrosis (CF). During early infection P. aeruginosa produces multiple virulence factors, which cause acute pulmonary disease and are largely regulated by quorum sensing (QS) intercellular signalling networks. Longitudinal clinical studies have observed the loss, through adaptive mutation, of QS and QS-related virulence in late chronic infection. Although the mechanisms are not understood, infection with QS mutants has been linked to a worse outcome for CF patients. By comparing QS-active and QS-inactive P. aeruginosa CF isolates, we have identified novel virulence factors and pathways associated with QS disruption. In particular, we noted factors implicating increased intra-phagocyte survival. Our data present novel targets as candidates for future CF therapies. Some of these targets are already the subject of drug development programmes for the treatment of other bacterial pathogens and may provide cross-over benefit to the CF population. This SuperSeries is composed of the SubSeries listed below.
2010-11-04 | GSE25130 | GEO
Project description:Pseudomonas aeruginosa airway infection is the primary cause of death in Cystic Fibrosis (CF). During early infection P. aeruginosa produces multiple virulence factors, which cause acute pulmonary disease and are largely regulated by quorum sensing (QS) intercellular signalling networks. Longitudinal clinical studies have observed the loss, through adaptive mutation, of QS and QS-related virulence in late chronic infection. Although the mechanisms are not understood, infection with QS mutants has been linked to a worse outcome for CF patients. By comparing QS-active and QS-inactive P. aeruginosa CF isolates, we have identified novel virulence factors and pathways associated with QS disruption. In particular, we noted factors implicating increased intra-phagocyte survival. Our data present novel targets as candidates for future CF therapies. Some of these targets are already the subject of drug development programmes for the treatment of other bacterial pathogens and may provide cross-over benefit to the CF population. Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE25128: Gene expression data from Pseudomonas aeruginosa strains isolated from cystic fibrosis lung infections GSE25129: Comparative genomic hybridisation data from Pseudomonas aeruginosa strains isolated from cystic fibrosis lung infections
2010-11-04 | E-GEOD-25130 | biostudies-arrayexpress
Project description:Pseudomonas aeruginosa is an opportunistic human pathogen, infecting immuno-compromised patients and causing persistent respiratory infections in people affected from cystic fibrosis. Pseudomonas strain Pseudomonas aeruginosa PA14 shows higher virulence than Pseudomonas aeruginosa PAO1 in a wide range of hosts including insects, nematodes and plants but the precise cause of this difference is not fully understood. Little is known about the host response upon infection with Pseudomonas and whether or not transcription is being affected as a host defense mechanism or altered in the benefit of the pathogen. In this context the social amoeba Dictyostelium discoideum has been described as a suitable host to study virulence of Pseudomonas and other opportunistic pathogens.
2008-07-09 | E-TABM-464 | biostudies-arrayexpress
Project description:Pseudomonas aeruginosa is a common pathogen in the lungs of the cystic fibrosis patients. As infection develops the organism progressively adapts to its environment and its mode of pathogenesis alters, frequently including the loss of quorum sensing regulated virulence factors. We used microarrays to detail differences between two P. aeruginosa isolates from CF patients, one of which (UUPA38) exhibited an active quorum sensing system (QS+) typical of early acute infection while the other (UUPA85) was QS-compromised (QS-) typical of chronic CF-adapted infection.
2010-11-04 | GSE25128 | GEO
Project description:Pseudomonas aeruginosa is a common pathogen in the lungs of the cystic fibrosis patients. As infection develops the organism progressively adapts to its environment and its mode of pathogenesis alters, frequently including the loss of quorum sensing (QS) regulated virulence factors. We used microarrays to determine genomic differences by comparative genome hybridisation between two P. aeruginosa isolates from CF patients, one of which exhibited an active quorum sensing (QS) system (UUPA38) typical of early acute infection while the other was QS-compromised (UUPA85) typical of chronic CF-adapted infection.
2010-11-04 | GSE25129 | GEO
Project description:Intercellular signal indole and its derivative hydroxyindoles inhibit Escherichia coli biofilm and diminish Pseudomonas aeruginosa virulence. However, indole and bacterial indole derivatives were unstable in microbial community due to the widespread of diverse oxygenases that could quickly degrade them. Hence, we sought to identify novel non-toxic, stable, and potent indole derivatives from plant sources for inhibiting biofilm formation of E. coli O157:H7 and P. aeruginosa PAO1. Here, plant auxin 3-indolylacetonitrile (IAN) was found to inhibit biofilm formation of both E. coli O157:H7 and P. aeruginosa without affecting its growth. IAN inhibited biofilms more effectively than indole for both E. coli and P. aeruginosa. Additionally, IAN decreased the production of virulence factor pyocyanin in P. aeruginosa. DNA microarray analysis indicated that IAN repressed genes involved in curli formation and glycerol metabolism, while IAN induced indole-related genes and prophage genes in E. coli. It appears that IAN inhibits biofilm formation of E. coli by reducing curli formation and inducing indole production. Furthermore, unlike bacterial indole derivatives, plant-originated IAN was stable in the presence of either E. coli or P. aeruginosa.
2011-02-20 | GSE21508 | GEO
Project description:Pseudomonas aeruginosa is a common pathogen in the lungs of the cystic fibrosis patients. As infection develops the organism progressively adapts to its environment and its mode of pathogenesis alters, frequently including the loss of quorum sensing regulated virulence factors. We used microarrays to detail differences between two P. aeruginosa isolates from CF patients, one of which (UUPA38) exhibited an active quorum sensing system (QS+) typical of early acute infection while the other (UUPA85) was QS-compromised (QS-) typical of chronic CF-adapted infection. Bacterial cell biomass was harvested from triplicate biofilm and planktonic cultures of each of 2 strains of P. aeruginosa. RNA was extracted, converted to cDNA and hybridized to Affymetrix microarrays. We aimed to identify genes which were differentially transcribed between the 2 isolates during both modes of growth.
2010-11-04 | E-GEOD-25128 | biostudies-arrayexpress
Project description:Pseudomonas aeruginosa is a significant opportunistic pathogen responsible for numerous human infections. Its high pathogenicity resides in a diverse array of virulence factors and an ability to adapt to hostile environments. We report that these factors are tied to the activity of condensins, SMC and MksBEF, which primarily function in structural chromosome maintenance. This study revealed that both proteins are required for P. aeruginosa virulence during corneal infection. The reduction in virulence was traced to broad changes in gene expression. Transcriptional signatures of smc and mksB mutants were largely dissimilar and non-additive, with the double mutant displaying a distinct gene expression profile. Affected regulons included those responsible for lifestyle control, primary metabolism, surface adhesion and biofilm growth, iron and sulfur assimilation, and numerous virulence factors, including type 3 and type 6 secretion systems. The in vitro phenotypes of condensin mutants mirrored their transcriptional profiles and included impaired production and secretion of multiple virulence factors, growth deficiencies under nutrient limiting conditions, and altered c-di-GMP signaling. Notably, c-di-GMP mediated some but not all transcriptional responses of the mutants. Thus, condensins are integrated into the control of multiple genetic programs related to epigenetic and virulent behavior of P. aeruginosa.
2022-01-05 | GSE161971 | GEO