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  3. The combination of insulin and linezolid ameliorates Staphylococcus aureus pneumonia in individuals with diabetes via the TLR2/MAPKs/NLRP3 pathway

The combination of insulin and linezolid ameliorates Staphylococcus aureus pneumonia in individuals with diabetes via the TLR2/MAPKs/NLRP3 pathway

  • Int J Biol Macromol. 2023 May 7;124750. doi: 10.1016/j.ijbiomac.2023.124750.
Lihui Ni 1,  Yuan Li 1,  Haifeng Zhang 1,  Yunxiao Ma 1,  Yuli Song 2,  Xudong Tang 3,  Junwen Fan 4,  Jin Yang Shi 1,  Xinhua Cui 1,  Hongyue Xu 1,  Hong Zhou 1,  Keshu Shen 5,  Weiying Guo 6,  Lu Yu 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Human-Animal Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine Jilin University, Department of Endocrinology and Department of Interventional Therapy of First Hospital of Jilin University, Changchun 130062, China.
  • 2 Shenzhen Liyunde Biotechnology Co., Ltd., Shenzhen 518057, China.
  • 3 Key Lab for New Drug Research of TCM, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057, China.
  • 4 Beijing Center for Animal Disease Control and Prevention, Beijing 102629, China.
  • 5 Jilin Hepatobiliary Hospital, Changchun 130062, China.
  • 6 State Key Laboratory of Human-Animal Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine Jilin University, Department of Endocrinology and Department of Interventional Therapy of First Hospital of Jilin University, Changchun 130062, China. Electronic address: guowy@jlu.edu.cn.
  • 7 State Key Laboratory of Human-Animal Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine Jilin University, Department of Endocrinology and Department of Interventional Therapy of First Hospital of Jilin University, Changchun 130062, China. Electronic address: yu_lu@jlu.edu.cn.
PMID: 37160172 DOI: 10.1016/j.ijbiomac.2023.124750
Abstract

Diabetes mellitus (DM) complicated with Staphylococcus aureus (S. aureus) Infection lacks effective treatment strategies. In this study, we found that Insulin combined with linezolid has potential to deal with the thorny problem. In vitro, our drug sensitivity assay, Bacterial growth curve and hemolytic tests showed that a combination of Insulin and linezolid exerted good Antibacterial and anti-α-hemolysin activity, CCK8 experiment, glucose content and glycogen content determination showed that the combination of Insulin and linezolid increased murine macrophage survival rate and reduced the extracellular glucose level of high glucose-treated MH-S cells and intracellular glycogen level, and Western blot showed that the combination inhibited TLR2/MAPKs/NLRP3-related inflammatory pathways in MH-S cells. The results of in vivo experiments showed that the combination therapy stabilized glucose level, remained body weight, ameliorated lung injury including improving pulmonary edema and decreasing lung wet/dry weight ratio, reduced the CFUs and inflammation in the lung tissue in a mouse model of diabetes with S. aureus pneumonia, and inhibited the expression of TLR2, MAPKs and NLRP3 inflammatory pathway. Overall, the combination of Insulin and linezolid as autolytic inhibitor exhibited the effects of significant Antibacterial and improving glucose level in vitro and in vivo, and also has an anti-inflammation activity via the TLR2/MAPKs/NLRP3 pathway, this paves the way for new treatments for diabetes mellitus complicated with S. aureus Infection.

Keywords

Autolytic inhibitor; Diabetic pneumonia; Insulin; Linezolid; Staphylococcus aureus.

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