Mr. Erasmus Wilson.

Wilson, Erasmus

doi:10.1016/s0140-6736(02)68928-7

Cited by 3 publications

(6 citation statements)

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“…This metabolite could be the active colibactin genotoxin. This scenario is consistent with previous observations that pks + E. coli promote interstrand cross-link formation in linearized plasmid DNA and human cell lines, 8,9 as well as a recent finding that a synthetic 'colibactin mimic' containing two cyclopropane rings cross-links DNA in vitro, while a monomer cannot. 32 This proposal is also consistent with our current understanding of colibactin-mediated DNA damage.…”

Section: Resultssupporting

confidence: 92%

“…We previously identified and characterized a pair of diasteromeric colibactin-derived DNA adducts 18that likely arise from degradation of a larger lesion. 9 Depurination of the proposed colibactin-DNA cross-link 19 would give adduct 20, which could undergo oxidative cleavage to give monoadducts 21 and 18 ( Figure 7A). A similar cleavage has been shown to occur readily in model substrates and a synthetic colibactin mimic.…”

Section: Resultsmentioning

confidence: 99%

“…[5][6][7] Recent studies have indicated colibactin's genotoxicity likely arises from a direct interaction with DNA, as we and others have reported the accumulation of interstrand cross-links in human cell lines incubated with pks + E. coli. 8,9 Cell lines with impaired interstrand cross-link repair are also more sensitive to colibactin exposure. 8 However, the underlying chemical and enzymatic basis for colibactin's DNA cross-linking activity remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…[21][22] Formation of an α,β-unsaturated imine after cleaving the prodrug motif in precolibactin likely enhances the electrophilicity of the cyclopropane toward DNA bases, and the recent identification and structural characterization of colibactin-derived DNA adducts in human cells and colonic epithelial cells provided support for this functional group serving as an electrophilic warhead. 9,23 However, it was unclear how this structural motif could lead to generation of an interstrand cross-link.…”

Section: Introductionmentioning

confidence: 99%

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Reactivity of an Unusual Amidase May Explain Colibactin’s DNA Cross-Linking Activity

et al. 2019

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Certain commensal and pathogenic bacteria produce colibactin, a small molecule genotoxin that causes interstrand cross-links in host cell DNA. Though colibactin alkylates DNA, the molecular basis for cross-link formation is unclear. Here, we report that the colibactin biosynthetic enzyme ClbL is an amide bond-forming enzyme that links aminoketone and β-keto thioester substrates in vitro and in vivo. The substrate specificity of ClbL strongly supports a role for this enzyme in terminating the colibactin NRPS-PKS assembly line and incorporating two electrophilic cyclopropane warheads into the final natural product scaffold. This proposed transformation was supported by the detection of a colibactin-derived cross-linked DNA adduct. Overall, this work provides a biosynthetic explanation for colibactin's DNA cross-linking activity and paves the way for further study of its chemical structure and biological roles.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reactivity of an Unusual Amidase May Explain Colibactin’s DNA Cross-Linking Activity

et al. 2019

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“…This demonstrated how human gut microbiota composition can be connected to carcinogenesis. [2][3][4] In insects, volatile metabolites emitted from microbemicrobe interactions constitute a symbiotic relationship modulating insect behavior. 5 Leaf cutting ants harbor symbiotic actinomycetes on their carapace that produce antifungal compounds, which allow the ants to prevent pathogenic strains from invading the fungal gardens they use as a food source.…”

Section: Graphical Abstractmentioning

confidence: 99%

Spatiochemically Profiling Microbial Interactions with Membrane Scaffolded Desorption Electrospray Ionization-Ion Mobility-Imaging Mass Spectrometry and Unsupervised Segmentation

Ellis¹,

Fischer²,

Martin

et al. 2019

Anal. Chem.

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Imaging the inventory of microbial small molecule interactions provides important insights into microbial chemical ecology and human medicine. Herein we demonstrate a new method for enhanced detection and analysis of metabolites present in interspecies interactions of microorganisms on surfaces. We demonstrate that desorption electrospray ionization-imaging mass spectrometry (DESI-IMS) using microporous membrane scaffolds (MMS) enables enhanced spatiochemical analyses of interacting microbes among tested sample preparation techniques. Membrane scaffolded DESI-IMS has inherent advantages compared to matrix-assisted laser desorption ionization (MALDI) and other IMS methods through direct IMS analyses of microbial chemistry in situ. This rapid imaging method yields sensitive MS analyses with unique m/z measurements when compared to liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) via unmediated sampling by MMS DESI-IMS. Unsupervised segmentation imaging analysis of acquired DESI-IMS data reveals distinct chemical regions corresponding to intermicrobial phenomenon such as predation and communication. We validate the method by linking Myxovirescin A and DKxanthene-560 to their known biological roles of predation and phase variation, respectively. In addition to providing the first topographic locations of known natural products, we prioritize 54 unknown features using segmentation within the region of predation. Thus, DESI-IMS and unsupervised segmentation spatially annotates the *

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‘To Preserve the Skin in Health’: Drainage, Bodily Control and the Visual Definition of Healthy Skin 1835–1900

Hennepe

2014

Med. Hist.

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The concept of a healthy skin penetrated the lives of many people in late-nineteenth-century Britain. Popular writings on skin and soap advertisements are significant for pointing to the notions of the skin as a symbolic surface: a visual moral ideal. Popular health publications reveal how much contemporary understanding of skin defined and connected ideas of cleanliness and the visual ideals of the healthy body in Victorian Britain. Characterised as a 'sanitary commissioner' of the body, skin represented the organ of drainage for body and society. The importance of keeping the skin clean and purging it of waste materials such as sweat and dirt resonated in a Britain that embraced city sanitation developments, female beauty practices, racial identities and moral reform. By focusing on the popular work by British surgeon and dermatologist Erasmus Wilson (1809-84), this article offers a history of skin through the lens of the sanitary movement and developments in the struggle for control over healthy skin still in place today.

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Mr. Erasmus Wilson.

Cited by 3 publications

References 0 publications

Reactivity of an Unusual Amidase May Explain Colibactin’s DNA Cross-Linking Activity

Reactivity of an Unusual Amidase May Explain Colibactin’s DNA Cross-Linking Activity

Spatiochemically Profiling Microbial Interactions with Membrane Scaffolded Desorption Electrospray Ionization-Ion Mobility-Imaging Mass Spectrometry and Unsupervised Segmentation

‘To Preserve the Skin in Health’: Drainage, Bodily Control and the Visual Definition of Healthy Skin 1835–1900

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