Keratin 6a reorganization for ubiquitin–proteasomal processing is a direct antimicrobial response

Chan, Jimmy W.M.; Yuen, Don; Too, Priscilla Hiu Mei; Sun, Yan; Willard, Belinda; Man, David; Tam, Connie

doi:10.1083/jcb.201704186

Cited by 24 publications

(21 citation statements)

References 93 publications

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“…The decrease in K6a is of particular interest in view of the recent discovery of antimicrobial peptides (AMP) derived from cytoplasmic proteasome processing of K6a in the corneal epithelium in response to exposure to microbially derived ligands. 13 The observed infection-induced reduction of the parental K6a in this model may thus result in decrease in AMP production and persistence of infection.…”

Section: Discussionmentioning

confidence: 78%

“…This ex vivo model uses human skin and demonstrates how wound infection impairs healing, by the upregulation of innate skin inflammatory responses, and the downregulation of the expression of genes involved in the repair process. The decrease in K6a is of particular interest in view of the recent discovery of antimicrobial peptides (AMP) derived from cytoplasmic proteasome processing of K6a in the corneal epithelium in response to exposure to microbially derived ligands . The observed infection‐induced reduction of the parental K6a in this model may thus result in decrease in AMP production and persistence of infection.…”

Section: Discussionmentioning

confidence: 96%

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A tractable, simplified ex vivo human skin model of wound infection

Yoon

Fregoso

Nguyen

et al. 2019

Wound Repair Regeneration

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The prevalence of infection in chronic wounds is well documented in the literature but not optimally studied due to the drawbacks of current methodologies. Here, we describe a tractable and simplified ex vivo human skin model of infection that addresses the critical drawbacks of high costs and limited translatability. Wounds were generated from excised abdominal skin from cosmetic procedures and cultured, inoculated with Staphylococcus aureus strain UAMS‐1, or under aseptic conditions. After three days, the infected wounds exhibited biofilm formation and significantly impaired reepithelialization compared to the control. Additionally, promigratory and proreparative genes were significantly downregulated, while proinflammatory genes were significantly upregulated, demonstrating molecular characterizations of impaired healing as in chronic wounds. This model allows for a simplified and versatile tool for the study of wound infection and subsequent development of novel therapies.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 96%

A tractable, simplified ex vivo human skin model of wound infection

Yoon

Fregoso

Nguyen

et al. 2019

Wound Repair Regeneration

View full text Add to dashboard Cite

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“…The latter are also expressed by THIO 49 , 50 . Ubiquitin peptide 52 (RL40) shows involvement of the proteasome system during keratinocyte proliferation 51 , whilst this is also confirmed by the co-expression of keratin 6b (K2C6B) 52 . Functioning of other members of the here reported fingermark proteome in regards to the biochemistry of skin surface material could not be inferred from the literature and, yet, remain elusive.…”

Section: Discussionmentioning

confidence: 87%

Proteomics as a new tool to study fingermark ageing in forensics

Oonk

Schuurmans

Pabst

et al. 2018

Sci Rep

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Fingermarks are trace evidence of great forensic importance, and their omnipresence makes them pivotal in crime investigation. Police and law enforcement authorities have exploited fingermarks primarily for personal identification, but crucial knowledge on when fingermarks were deposited is often lacking, thereby hindering crime reconstruction. Biomolecular constituents of fingermark residue, such as amino acids, lipids and proteins, may provide excellent means for fingermark age determination, however robust methodologies or detailed knowledge on molecular mechanisms in time are currently not available. Here, we address fingermark age assessment by: (i) drafting a first protein map of fingermark residue, (ii) differential studies of fresh and aged fingermarks and (iii), to mimic real-world scenarios, estimating the effects of donor contact with bodily fluids on the identification of potential age biomarkers. Using a high-resolution mass spectrometry-based proteomics approach, we drafted a characteristic fingermark proteome, of which five proteins were identified as promising candidates for fingermark age estimation. This study additionally demonstrates successful identification of both endogenous and contaminant proteins from donors that have been in contact with various bodily fluids. In summary, we introduce state-of-the-art proteomics as a sensitive tool to monitor fingermark aging on the protein level with sufficient selectivity to differentiate potential age markers from body fluid contaminants.

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“…One defense mechanism commonly used by these epithelia is the production of antimicrobial peptides that can kill invading pathogens and activate the host immune response (1). In this issue, Chan et al describe how, in response to bacterial ligands, corneal epithelial cells generate antimicrobial peptides from their keratin 6a intermediate fi laments (2).…”

Section: In Focusmentioning

confidence: 99%

“…Tam and colleagues, led by research scientist Jonathan Chan, fi rst examined how the fi lamentous keratin network of corneal epithelial cells responded to the presence of bacterial surface molecules, such as LPS, fl agellin, or lipoteichoic acid, that can be detected by host cell Toll-like receptors (2). "When cells were exposed to these bacterial ligands, the fi lamentous network seemed to disassemble because it appeared more diffuse," Tam says.…”

Section: In Focusmentioning

confidence: 99%