Progress made in the field of biological 3D quantitative imaging

ON2022-11-24TAG: ShanghaiTech UniversityCATEGORY: Center for Transformative Science

Staphylococcus aureus is a widespread Gram-positive pathogenic bacterium and is regarded as the main cause of skin and soft tissue infections. Due to the widespread use of antibiotics to kill bacteria, antibiotic-resistant bacteria have emerged. Functional metal nanoclusters can specifically detect S. aureus and exhibit antibacterial activity, which is favored as a “green” sterilization method that does not lead to drug resistance. However, there are few quantitative analysis methods for the three-dimensional (3D) structure of intact microbial cells, which provide intuitive evidence for bacterial inactivation following incubation with Au-cluster probes.

Recently, a joint research team led by SPST/CTS Professor Jiang Huaidong from ShanghaiTech University, in collaboration with Professor Gao Xueyun from Beijing University of Technology, achieved a breakthrough in the field of 3D spatial structural analysis of S. aureus to explore the microbe-inhibitor drug interactions at nanoscale. By combing the X-ray coherent diffraction imaging (CDI) and tomography methods, the 3D structure of S. aureus treated with peptide-mineralized Au-clusters were revealed in situ. Taking the advantages of high-resolution quantitative imaging, the interaction between bacteria and their specific inhibitory drugs was demonstrated, providing a new tool and new ideas for exploring the mechanism of drug action.

During the study, the team performed specific targeting performance of Au-cluster probes against S. aureus and confirmed that the Au-cluster probes has dose-dependent bactericidal activity in vitro. Then, the CDI method was used to perform 3D high-resolution quantitative imaging of probe-treated S. aureus cells (with a 3D resolution of 47 nm), revealing the surface and internal structure of S. aureus at the nanoscale. Compared with the untreated S. aureus, the surface of probe-treated S. aureus has obvious concave holes, the surface to volume ratios is increased, the electron density is decreased, and the loss of bacterial cytoplasmic components is significant, resulting in complete cell collapse and folding of the cell wall. Therefore, with the advantages of the novel CDI method in high-resolution quantitative bioimaging, this study was able to visually demonstrate the antibacterial mechanisms of Au-cluster probes.

The research results were published in the paper entitled “Three-Dimensional Quantitative Coherent Diffraction Imaging of Staphylococcus aureus Treated with Peptide-Mineralized Au-Cluster Probes” in the journal Analytical Chemistry as a cover article. The fifth-year graduate students Li Tangmeng and He Bo are the co-first authors. Research Associate Professor Fan Jiadong, Prof. Jiang Huaidong and Prof. Gao Xueyun are the co-corresponding authors. 

**The news article is provided by Prof. Jiang Huaidong