Detection of Bacterial Neutral Ceramidase in Diabetic Foot Ulcers with an Optimized Substrate and Chemoenzymatic Probes
Abstract: Ceramidases (CDases) are important in controlling skin barrier integrity by regulating ceramide composition and affording downstream signal molecules. While the functions of epidermal CDases are known, roles of neutral CDases secreted by skin‐residing microbes are undefined. Here, we developed a one‐step fluorogenic substrate, S‐B, for specific detection of bacterial CDase activity and inhibitor screening. We identified a non‐hydrolyzable substrate mimic, C6, as the best hit. Based on C6, we designed a photoaffinity probe, JX‐1, which efficiently detects bacterial CDases. Using JX‐1, we identified endogenous low‐abundance PaCDase in a P. aeruginosa monoculture and in a mixed skin bacteria culture. Harnessing both S‐B and JX‐1, we found that CDase activity positively correlates with the relative abundance of P. aeruginosa and is negatively associated with wound area reduction in clinical diabetic foot ulcer patient samples. Overall, our study demonstrates that bacterial CDases are important regulators of skin ceramides and potentially play a role in wound healing.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Detection of Bacterial Neutral Ceramidase in Diabetic Foot Ulcers with an Optimized Substrate and Chemoenzymatic Probes ; day:10 ; month:07 ; year:2023 ; extent:10
Angewandte Chemie / International edition. International edition ; (10.07.2023) (gesamt 10)
- Urheber
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Zou, Jiao Xia
Chua, Wisely
Ser, Zheng
Wang, Shi Mei
Chiang, Grace Shu Hui
Sanmugam, Kavitha
Tan, Boon Yeow
Sobota, Radoslaw M.
Li, Hao
- DOI
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10.1002/anie.202307553
- URN
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urn:nbn:de:101:1-2023071115232398148946
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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14.08.2025, 11:04 MESZ
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Beteiligte
- Zou, Jiao Xia
- Chua, Wisely
- Ser, Zheng
- Wang, Shi Mei
- Chiang, Grace Shu Hui
- Sanmugam, Kavitha
- Tan, Boon Yeow
- Sobota, Radoslaw M.
- Li, Hao
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