Zou, J. X., Chua, W., Ser, Z., Wang, S. M., Chiang, G. S. H., Sanmugam, K., Tan, B. Y., Sobota, R. M., & Li, H. (2023). Detection of Bacterial Neutral Ceramidase in Diabetic Foot Ulcers with an Optimized Substrate and Chemoenzymatic Probes. Angewandte Chemie, 135(33). Portico. https://doi.org/10.1002/ange.202307553
Abstract:
AbstractCeramidases (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.
License type:
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Funding Info:
This research / project is supported by the Ministry of Education - AcRF Tier 1
Grant Reference no. : R-143-000-B79-114
This research / project is supported by the MOE - AcRF Tier 1
Grant Reference no. : R-143-000-C16-114
This research / project is supported by the A*STAR - Industry Alignment Fund-Pre-Positioning grant
Grant Reference no. : H19/01/a0/0GG9
This research / project is supported by the National Medical Research Council/ Ministry of Education - Open Fund-Individual Research Grant
Grant Reference no. : MOH-000612-00