Key role of an ADP − ribose - dependent transcriptional regulator of NAD metabolism for fitness and virulence of Pseudomonas aeruginosa

Okon, Elza; Dethlefsen, Sarah; Pelnikevich, Anna; Barneveld, Andrea van; Munder, Antje; Tümmler, Burkhard

doi:10.1016/j.ijmm.2016.09.007

Cited by 19 publications

(24 citation statements)

References 49 publications

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“…As shown on Fig. , the strongest upregulation is that of the PA4918‐PA4920 operon, which contains an enzyme involved in NAD biosynthesis (Okon et al ., ). Another operon specifically upregulated during PA5oct infection encodes a part of the psl A‐L gene cluster ( pslE‐J ), which is involved in the production of Psl exopolysaccharide (Jackson et al ., ).…”

Section: Resultsmentioning

confidence: 97%

Integrative omics analysis of Pseudomonas aeruginosa virus PA5oct highlights the molecular complexity of jumbo phages

Lood

Danis-Wlodarczyk

Blasdel

et al. 2020

Environmental Microbiology

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Pseudomonas virus vB_PaeM_PA5oct is proposed as a model jumbo bacteriophage to investigate phage-bacteria interactions and is a candidate for phage therapy applications. Combining hybrid sequencing, RNA-Seq and mass spectrometry allowed us to accurately annotate its 286,783 bp genome with 461 coding regions including four noncoding RNAs (ncRNAs) and 93 virion-associated proteins. PA5oct relies on the host RNA polymerase for the infection cycle and RNA-Seq revealed a gradual take-over of the total cell transcriptome from 21% in early infection to 93% in late infection. PA5oct is not organized into strictly contiguous regions of temporal transcription, but some genomic regions transcribed in early, middle and late phases of infection can be discriminated. Interestingly, we observe regions showing limited transcription activity throughout the infection cycle. We show that PA5oct upregulates specific bacterial operons during infection including operons pncA-pncB1-nadE involved in NAD biosynthesis, psl for exopolysaccharide biosynthesis and nap for periplasmic nitrate reductase production. We also observe a downregulation of T4P gene products suggesting mechanisms of superinfection exclusion. We used the proteome of PA5oct to position our isolate amongst other phages using a gene-sharing network. This integrative omics study illustrates the molecular diversity of jumbo viruses and raises new questions towards cellular regulation and phage-encoded hijacking mechanisms. ; Tel. +32 16 37 95 24; Fax +32 16 3 21965. † These authors contributed equally to this work.

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Section: Resultsmentioning

confidence: 97%

Integrative omics analysis of Pseudomonas aeruginosa virus PA5oct highlights the molecular complexity of jumbo phages

Lood

Danis-Wlodarczyk

Blasdel

et al. 2020

Environmental Microbiology

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“…The extent of inflammation caused by the ΔPA4916 mutant correlated with the ability of this strain to colonize the lungs of infected mice. A recent study has also shown that PA4916 plasposon mutagenesis abrogated virulence of a robust mucoid P. aeruginosa cystic fibrosis airway isolate and named PA4916 as NrtR (Okon et al, 2017). So we further explored the regulation mechanism of PA4916 on the T3SS and referred PA4916 as NrtR hereafter.…”

Section: Resultsmentioning

confidence: 99%

“…NrtR encodes a transcriptional regulator which binds to the DNA intergenic region between the nadD2 - nrtR and PA4918-4920 operons to repress their expression (Okon et al, 2017). RT-qPCR assay showed that the mRNA levels of nadD2 and PA4918 in the Δ nrtR mutant were much higher than those in PAK (Figure 6A and Supplementary Figure S3A).…”

Section: Resultsmentioning

confidence: 99%

NrtR Regulates the Type III Secretion System Through cAMP/Vfr Pathway in Pseudomonas aeruginosa

et al. 2019

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The type III secretion system (T3SS) plays an important role in the pathogenesis of Pseudomonas aeruginosa. Expression of the T3SS is controlled under a complicate regulatory network. In this study, we demonstrate that NrtR (PA4916) is involved in the T3SS expression and pathogenesis of P. aeruginosa in a mouse acute pneumonia model. Overexpression of the T3SS central activator ExsA or exogenous supplementation of cAMP restored the expression of T3SS in the ΔnrtR mutant, suggesting that NrtR might regulate T3SS through the cAMP-Vfr signaling pathway. Further experiments demonstrated that the decrease of cAMP content is not due to the expression change of adenylate cyclases or phosphodiesterase in the ΔnrtR mutant. As it has been shown that nadD2 is upregulated in the ΔnrtR mutant, we overexpressed nadD2 in wild type PAK, which reduced the intracellular cAMP level and the expression of the T3SS genes. Meanwhile, deletion of nadD2 in the ΔnrtR mutant restored the expression and secretion of the T3SS. Co-immunoprecipitation assay revealed an interaction between NadD2 and the catalytic domain of the adenylate cyclase CyaB. Further in vitro assay indicated that NadD2 repressed the enzymatic activity of CyaB. Therefore, we have identified a novel regulatory mechanism of T3SS in P. aeruginosa.

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“…Thanks to the application of omics technologies, we have gained insight into P. aeruginosa ’s genome organisation and diversity 8 , 10 , 11 , 22 , 100 , habitat-specific transcriptome 101 – 105 , proteome 106 – 108 , and metabolome 108 – 112 and the co-evolution of P. aeruginosa with competitors in human habitats such as Staphylococcus aureus 113 – 115 . The function of hundreds of previously uncharacterised “conserved hypotheticals” 11 and the structure of secretory nanomachines have been resolved 37 , 41 , 116 – 121 and knowledge has been gained about the complex regulation of the release of exopolysaccharides, secondary metabolites, and virulence effectors 1 .…”

Section: Looking Back Forwardmentioning

confidence: 99%

Recent advances in understanding Pseudomonas aeruginosa as a pathogen

2017

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The versatile and ubiquitous Pseudomonas aeruginosa is an opportunistic pathogen causing acute and chronic infections in predisposed human subjects. Here we review recent progress in understanding P. aeruginosa population biology and virulence, its cyclic di-GMP-mediated switches of lifestyle, and its interaction with the mammalian host as well as the role of the type III and type VI secretion systems in P. aeruginosa infection.

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Key role of an ADP − ribose - dependent transcriptional regulator of NAD metabolism for fitness and virulence of Pseudomonas aeruginosa

Cited by 19 publications

References 49 publications

Integrative omics analysis of Pseudomonas aeruginosa virus PA5oct highlights the molecular complexity of jumbo phages

Integrative omics analysis of Pseudomonas aeruginosa virus PA5oct highlights the molecular complexity of jumbo phages

NrtR Regulates the Type III Secretion System Through cAMP/Vfr Pathway in Pseudomonas aeruginosa

Recent advances in understanding Pseudomonas aeruginosa as a pathogen

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