『Cover Story』Unveiling the mystery of SCV resistance: new discoveries on hpt gene mutation and purine metabolism!

10 December 2024

Tingwang Shi, Qiong Wu, Zesong Ruan, Zhiyuan Luo, Wenbo Wang, Zhao Guo, Yihong Ma, Xin Wang, Guangyu Chu, Han Lin, Min Ge, Yunfeng Chen

The cover of this issue of Advanced Science is "Resensitizing β-Lactams by Reprogramming Purine Metabolism in Small Colony Variant for Osteomyelitis Treatment" published by Professor Chen Yunfeng from the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and Dr. Ge Min from the University of Hong Kong.

Research background

Small colony variant (SCV) is a special bacterial subgroup that is closely related to the persistence of antibiotic resistance and osteomyelitis. However, the intrinsic phenotypic instability of SCV has always hindered the in-depth study of its pathogenic mechanism. This instability of SCV makes it difficult for scientists to stably study its characteristics under laboratory conditions, thus limiting the comprehensive understanding of its resistance and pathogenicity.

Research significance

This study successfully isolated phenotypically stable SCV strains from clinical specimens, providing stable experimental materials for in-depth study of the pathogenic mechanism and drug resistance of SCV. Through multi-omics analysis, the study found that the high drug resistance of SCV is related to changes in its purine metabolic pathway, especially due to mutations in the hypoxanthine phosphoribosyltransferase (hpt) gene. This finding provides a new perspective for understanding the drug resistance mechanism of SCV.

This study innovatively found that lonidamine, an inhibitor of cellular energy metabolism, can effectively reduce SCV's resistance to β-lactam antibiotics, thereby contributing to its eradication. This discovery provides a new therapeutic strategy for the treatment of SCV-related diseases. A co-delivery system of londamin and oxacillin with amino-modified dendritic mesoporous silica as carrier was also constructed. The system showed high efficacy and safety in both in vitro and in vivo experiments, providing strong support for clinical application.

Research Prospects

Future studies can further explore how hpt gene mutations affect the purine metabolic pathway and how this metabolic change leads to increased SCV resistance. At the same time, it can also be studied how londamin can alleviate SCV resistance by reprogramming purine metabolism. In addition to osteomyelitis, SCV is also associated with a variety of infectious diseases. Future studies can explore the application of this treatment strategy in the treatment of other SCV-related infectious diseases. Based on a deeper understanding of the current mechanism, new drugs or therapies targeting SCV resistance can be developed to more effectively treat SCV-related diseases.

Cover Design Process

• The design of the cover is closely centered around the theme of the paper, which is "Restoring the sensitivity of β-lactam antibiotics to treat osteomyelitis by reshaping the purine metabolism of small molecule colony variants (SCVs)". The center of the cover highlights the core content of the paper, namely the SCV strain, changes in purine metabolism, and the mechanism of drug action. This design method intuitively conveys the research focus and findings of the paper, allowing readers to grasp the core of the paper at first glance.
• The color matching of the cover mainly uses cool tones, such as blue and white, which is consistent with the calm and objective nature of scientific research. At the same time, blue also represents science, technology and the future, which echoes the cutting-edge nature of the paper. White gives people a pure and clear feeling, making the cover more concise and clear. In addition, there are some dark areas in the cover, such as the background of the title and the shadow part of the molecular structure. These dark areas add a touch of mystery to the cover, suggesting the unknown and exploratory nature of scientific research.
• The style of the cover is mainly simple and generous, without too much decoration and redundant elements. The entire cover is mainly based on molecular structure and drug molecules, with a short title and author information, making the entire cover look very professional and neat. This style is consistent with the rigor and authority of scientific journals, and also allows readers to focus more on the content of the paper. In the end, the cover was highly recognized by teachers and journal editors and was successfully published!