PAMDB: a comprehensive Pseudomonas aeruginosa metabolome database

Huang, Weiliang; Brewer, Luke K.; Jones, Jace W.; Nguyen, Angela T.; Marcu, Ana; Wishart, David S.; Oglesby-Sherrouse, Amanda G.; Kane, Maureen A.; Wilks, Angela

doi:10.1093/nar/gkx1061

Cited by 52 publications

(43 citation statements)

References 53 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PAMDB [85] is a comprehensive Pseudomonas aeruginosa metabolome database, well-curated, with rich metadata and offering bulk download. However, it does not contain only NPs but also results of the primary metabolism, so it was not included in the COCONUT collection.…”

Section: Natural Products By the Taxonomy Of The Synthesizing Organismmentioning

confidence: 99%

Review on natural products databases: where to find data in 2020

2020

View full text Add to dashboard Cite

Natural products (NPs) have been the centre of attention of the scientific community in the last decencies and the interest around them continues to grow incessantly. As a consequence, in the last 20 years, there was a rapid multiplication of various databases and collections as generalistic or thematic resources for NP information. In this review, we establish a complete overview of these resources, and the numbers are overwhelming: over 120 different NP databases and collections were published and re-used since 2000. 98 of them are still somehow accessible and only 50 are open access. The latter include not only databases but also big collections of NPs published as supplementary material in scientific publications and collections that were backed up in the ZINC database for commercially-available compounds. Some databases, even published relatively recently are already not accessible anymore, which leads to a dramatic loss of data on NPs. The data sources are presented in this manuscript, together with the comparison of the content of open ones. With this review, we also compiled the open-access natural compounds in one single dataset a COlleCtion of Open NatUral producTs (COCONUT), which is available on Zenodo and contains structures and sparse annotations for over 400,000 non-redundant NPs, which makes it the biggest open collection of NPs available to this date.

show abstract

Section: Natural Products By the Taxonomy Of The Synthesizing Organismmentioning

confidence: 99%

Review on natural products databases: where to find data in 2020

2020

View full text Add to dashboard Cite

show abstract

“…Label-free quantifications were performed using an aligned AMRT (Accurate Mass and Retention Time) cluster quantification algorithm developed by Qi et al (78). Pathways and gene functions were analyzed with information from Pseudomonas genome database (76), KEGG database (79) and P. aeruginosa metabolome database (PAMDB) (80).…”

Section: Methodsmentioning

confidence: 99%

Proteomic analysis of thePseudomonas aeruginosairon starvation response reveals PrrF sRNA-dependent regulation of amino acid metabolism, iron-sulfur cluster biogenesis, motility, and zinc homeostasis

Nelson

Huang

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

Iron is a critical nutrient for most microbial pathogens, and the innate immune system exploits this requirement by sequestering iron and other metals through a process termed nutritional immunity. The opportunistic pathogen Pseudomonas aeruginosa provides a model system for understanding the microbial response to host iron depletion, as this organism exhibits a high requirement for iron as well as an exquisite ability to overcome iron deprivation during infection. Hallmarks of P. aeruginosa’s iron starvation response include the induction of multiple high affinity iron acquisition systems and an “iron sparing response” that is post-transcriptionally mediated by the PrrF small regulatory RNAs (sRNAs). Here, we used liquid chromatography-tandem mass spectrometry to conduct label-free proteomics of the P. aeruginosa iron starvation response, revealing several iron-regulated processes that have not been previously described. Iron starvation induced multiple proteins involved in branched chain and aromatic amino acid catabolism, providing the capacity for iron-independent entry of carbons into the TCA cycle. Proteins involved in sulfur assimilation and cysteine biosynthesis were reduced upon iron starvation, while proteins involved in iron-sulfur cluster biogenesis were paradoxically increased, highlighting the central role of iron in P. aeruginosa metabolism. Iron starvation also resulted in changes in the expression of several zinc-responsive proteins, as well as the first experimental evidence for increased levels of twitching motility proteins upon iron starvation. Subsequent proteomics analyses demonstrated that the PrrF sRNAs were required for iron regulation of many of these newly-identified proteins, and we identified PrrF complementarity with mRNAs encoding key iron-regulated proteins involved in amino acid metabolism, iron-sulfur biogenesis, and zinc homeostasis. Combined, these results provide the most comprehensive view of the P. aeruginosa iron starvation response to date and outline novel roles for the PrrF sRNAs in the P. aeruginosa iron sparing response and pathogenesis.AUTHOR SUMMARYIron is central for the metabolism of almost all microbial pathogens, and as such this element is sequestered by the host innate immune system to restrict microbial growth. Defining the response of microbial pathogens to iron starvation is therefore critical for understanding how pathogens colonize and propagate within the host. The opportunistic pathogen Pseudomonas aeruginosa, which causes significant morbidity and mortality in compromised individuals, provides an excellent model for studying this response due to its high requirement for iron yet well-documented ability to overcome iron starvation. Here we used label-free proteomics to investigate the P. aeruginosa iron starvation response, revealing a broad landscape of metabolic and metal homeostasis changes that have not previously been described. We further provide evidence that many of these processes are regulated through the iron responsive PrrF small regulatory RNAs, which are integral to P. aeruginosa iron homeostasis and virulence. These results demonstrate the power of proteomics for defining stress responses of microbial pathogens, and they provide the most comprehensive analysis to date of the P. aeruginosa iron starvation response.

show abstract

“…We sought to identify new ways of disrupting surface attachment through chemical means such as small molecules. P. aeruginosa produces many excreted metabolites with a wide array of functions (8). These secreted factors include virulence factors such as pyocyanin and rhamnolipids, as well as factors that regulate specific aspects of the P. aeruginosa life cycle like the biofilm dispersal cue, cis-2-decenoic acid (9).…”

Section: One Of the Major Causes Of A Wide Variety Of Hai's Is The Bamentioning

confidence: 99%

Pseudomonas aeruginosadetachment from surfaces via a self-made small molecule

Scheffler

Sugimoto

Bratton

et al. 2020

Preprint

View full text Add to dashboard Cite

Pseudomonas aeruginosa is a significant threat in both healthcare and industrial biofouling. Surface attachment of P. aeruginosa is particularly problematic as surface association induces virulence and biofilm formation, which hamper later antibiotic treatments. Previous efforts have searched for biofilm dispersal agents, but there are no known factors that specifically disperse surface-attached P. aeruginosa. In this study we develop a quantitative surface-dispersal assay and use it to show that P. aeruginosa itself produces factors that can stimulate its dispersal. Through bioactivity-guided fractionation, Mass Spectrometry, and Nuclear Magnetic Resonance, we elucidated the structure of one such factor, 2-methyl-4-hydroxyquinoline (MHQ). MHQ is an alkyl-quinolone with a previously unknown activity and is synthesized by the PqsABC enzymes. Pure MHQ is sufficient to disperse P. aeruginosa, but the dispersal activity of natural P. aeruginosa conditioned media requires additional factors. Whereas other alkyl quinolones have been shown to act as antibiotics or membrane depolarizers, MHQ lacks these activities and known antibiotics do not induce dispersal. In contrast, we show that MHQ inhibits the activity of Type IV Pili (TFP) and that TFP targeting can explain its dispersal activity. Our work thus identifies surface dispersal as a new activity of P. aeruginosa-produced small molecules, characterizes MHQ as a promising dispersal agent, and establishes TFP inhibition as a viable mechanism for P. aeruginosa dispersal.Significance StatementWe discovered that the clinically relevant human bacterial pathogen P. aeruginosa, typically associated with surface-based infections, is dispersed by a small molecule that the bacteria themselves produce. We elucidate the chemical structure of this molecule and find that mechanistically it functions to inhibit the activity of the P. aeruginosa extra cellular surface motility appendage, the type IV pilus.

show abstract

PAMDB: a comprehensive Pseudomonas aeruginosa metabolome database

Cited by 52 publications

References 53 publications

Review on natural products databases: where to find data in 2020

Review on natural products databases: where to find data in 2020

Proteomic analysis of thePseudomonas aeruginosairon starvation response reveals PrrF sRNA-dependent regulation of amino acid metabolism, iron-sulfur cluster biogenesis, motility, and zinc homeostasis

Pseudomonas aeruginosadetachment from surfaces via a self-made small molecule

Contact Info

Product

Resources

About