Evidence map›Paper›PMID 39656854›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Resensitizing β-Lactams by Reprogramming Purine Metabolism in Small Colony Variant for Osteomyelitis Treatment.

Tingwang Shi, Qiong Wu, Zesong Ruan, Zhiyuan Luo, Wenbo Wang, Zhao Guo, Yihong Ma, Xin Wang, Guangyu Chu, Han Lin and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Tingwang ShiDepartment of Orthopedic Surgery, Shanghai Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
Qiong WuDepartment of Laboratory Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
Zesong RuanDepartment of Orthopedic Surgery, Shanghai Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
Zhiyuan LuoDepartment of Orthopedic Surgery, Shanghai Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
Wenbo WangDepartment of Orthopedic Surgery, Shanghai Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
Zhao GuoDepartment of Orthopedic Surgery, Shanghai Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
Yihong MaDepartment of Orthopedic Surgery, Shanghai Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
Xin WangDepartment of Orthopedic Surgery, Shanghai Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
Guangyu ChuDepartment of Orthopedic Surgery, Spine Lab, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Han LinShanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai, 200050, China.
Min GeDepartment of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, 999077, China.ORCID https://orcid.org/0000-0001-6106-2721
Yunfeng ChenDepartment of Orthopedic Surgery, Shanghai Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.ORCID https://orcid.org/0000-0002-1612-5794

Funding

National Key R&D Program of China 2022YFB3804500National Natural Science Foundation of China 2002391National Natural Science Foundation of China 52372276National Natural Science Foundation of China 82172455Science and Technology Innovation Plan Of Shanghai Science and Technology Commission 22S31900200Shanghai Pilot Program for Basic Research-Chinese Academy of Science JCYJ-SHFY-2022-003Shanghai Shenkang Hospital Development Center SHDC12021117
6 · The paper itself

Abstract

Small colony variant (SCV) is strongly linked to antibiotic resistance and the persistence of osteomyelitis. However, the intrinsic phenotypic instability of SCV has hindered a thorough investigation of its pathogenic mechanisms. In this study, phenotypically stable SCV strains are successfully recovered from clinical specimens, characterized by elevated drug resistance and reduced immunogenicity. Multi-omics analysis revealed that the acquired high drug resistance is associated with altered flux in the purine metabolism pathway, attributable to mutations in the hypoxanthine phosphoribosyltransferase (hpt) gene. Furthermore, this study innovatively discovered that lonidamine, an inhibitor of cellular energy metabolism, can effectively mitigate SCV resistance to β-lactam antibiotics, thereby facilitating its eradication. The underlying mechanism involves the reprogramming of purine metabolism. Therefore, a co-delivery system for lonidamine and oxacillin is constructed with amino-modified dendritic mesoporous silica as a carrier, which showed high efficacy and safety in combating SCV both in vitro and in vivo experiments. Overall, this study elucidated the pathogenic mechanisms of a class of clinically isolated SCV isolates with hpt mutations and provided a paradigm for treating SCV-associated osteomyelitis by reprogramming purine metabolism.

Indexed as

Anti-Bacterial Agentsbeta-LactamsOsteomyelitisPurinesAnimalsDrug Resistance, BacterialHumansHypoxanthine PhosphoribosyltransferaseMiceStaphylococcus aureusAnti-Bacterial Agentsbeta-LactamsHypoxanthine PhosphoribosyltransferasepurinePurinesdrug deliverymetabolic reprogrammingosteomyelitissmall colony variantβ‐Lactam resistance

Identifiers

PMID39656854
PMCPMC11791937

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.