Mass spectral molecular networking of living microbial colonies

Watrous, Jeramie D.; Roach, Patrick J.; Alexandrov, Theodore; Heath, Brandi S.; Yang, Jianping; Kersten, Roland D.; Voort, Menno vander; Pogliano, Kit; Gross, Harald; Raaijmakers, Jos M.; Moore, Bradley S.; Laskin, Julia; Bandeira, Nuno; Dorrestein, Pieter C.

doi:10.1073/pnas.1203689109

Cited by 849 publications

(1,031 citation statements)

References 50 publications

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“…Pure standards were used for identification of metabolites through manual inspection of spectral peaks and matching of retention time and MS1 accurate mass, with confirmation of identification through comparison to MS/MS fragmentation patterns. For unknown metabolites, chemical networking was performed by Global Natural Products Social molecular networking (GNPS, http://gnps.ucsd.edu) and all visualization was performed in Cytoscape (Watrous et al., 2012). The data were clustered with a parent mass tolerance of 1.0 Da and a MS/MS fragment ion tolerance of 0.15 Da.…”

Section: Methodsmentioning

confidence: 99%

Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice

et al. 2018

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SummaryLongevity in mammals is influenced by sex, and lifespan extension in response to anti‐aging interventions is often sex‐specific, although the mechanisms underlying these sexual dimorphisms are largely unknown. Treatment of mice with 17‐α estradiol (17aE2) results in sex‐specific lifespan extension, with an increase in median survival in males of 19% and no survival effect in females. Given the links between lifespan extension and metabolism, we performed untargeted metabolomics analysis of liver, skeletal muscle and plasma from male and female mice treated with 17aE2 for eight months. We find that 17aE2 generates distinct sex‐specific changes in the metabolomic profile of liver and plasma. In males, 17aE2 treatment raised the abundance of several amino acids in the liver, and this was further associated with elevations in metabolites involved in urea cycling, suggesting altered amino acid metabolism. In females, amino acids and urea cycling metabolites were unaffected by 17aE2. 17aE2 also results in male‐specific elevations in a second estrogenic steroid—estriol‐3‐sulfate—suggesting different metabolism of this drug in males and females. To understand the underlying endocrine causes for these sexual dimorphisms, we castrated males and ovariectomized females prior to 17aE2 treatment, and found that virtually all the male‐specific metabolite responses to 17aE2 are inhibited or reduced by male castration. These results suggest novel metabolic pathways linked to male‐specific lifespan extension and show that the male‐specific metabolomic response to 17aE2 depends on the production of testicular hormones in adult life.

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Section: Methodsmentioning

confidence: 99%

Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice

et al. 2018

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“…Among these new approaches, molecular networking (MN) is a particularly effective one to organize MS/MS fragmentation spectra. MN compares all MS/MS spectra in a given extract and groups them according to their similarity (Watrous et al ., 2012; Bandeira, 2011; Liu et al ., 2013; Fang and Dorrestein, 2014). The application of these tools leads to the identification of novel compounds by avoiding re‐isolation of known compounds.…”

Section: Dereplication In Natural Product Discoverymentioning

confidence: 99%

Antibiotic drug discovery

Wohlleben

Mast

Stegmann

et al. 2016

Microbial Biotechnology

142

113

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SummaryDue to the threat posed by the increase of highly resistant pathogenic bacteria, there is an urgent need for new antibiotics; all the more so since in the last 20 years, the approval for new antibacterial agents had decreased. The field of natural product discovery has undergone a tremendous development over the past few years. This has been the consequence of several new and revolutionizing drug discovery and development techniques, which is initiating a ‘New Age of Antibiotic Discovery’. In this review, we concentrate on the most significant discovery approaches during the last and present years and comment on the challenges facing the community in the coming years.

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“…The metabolomic information, analyzed by molecular networking (Frank et al, 2008;Watrous et al, 2012;Yang et al, 2013), revealed a doubly charged ion at m/z 1107.053 in the wild type. The same peak was absent not only from the conprimycin mutant but also from the ectoine mutant (Supplementary Figure S6a).…”

Section: Disease Suppressiveness and Rhizosphere Colonization By Strementioning

confidence: 99%

Microbial and biochemical basis of a Fusarium wilt-suppressive soil

et al. 2015

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Crops lack genetic resistance to most necrotrophic pathogens. To compensate for this disadvantage, plants recruit antagonistic members of the soil microbiome to defend their roots against pathogens and other pests. The best examples of this microbially based defense of roots are observed in disease-suppressive soils in which suppressiveness is induced by continuously growing crops that are susceptible to a pathogen, but the molecular basis of most is poorly understood. Here we report the microbial characterization of a Korean soil with specific suppressiveness to Fusarium wilt of strawberry. In this soil, an attack on strawberry roots by Fusarium oxysporum results in a response by microbial defenders, of which members of the Actinobacteria appear to have a key role. We also identify Streptomyces genes responsible for the ribosomal synthesis of a novel heat-stable antifungal thiopeptide antibiotic inhibitory to F. oxysporum and the antibiotic’s mode of action against fungal cell wall biosynthesis. Both classical- and community-oriented approaches were required to dissect this suppressive soil from the field to the molecular level, and the results highlight the role of natural antibiotics as weapons in the microbial warfare in the rhizosphere that is integral to plant health, vigor and development.

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Mass spectral molecular networking of living microbial colonies

Cited by 849 publications

References 50 publications

Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice

Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice

Antibiotic drug discovery

Microbial and biochemical basis of a Fusarium wilt-suppressive soil

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