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ORIGINAL RESEARCH article

Front. Med.

Sec. Pulmonary Medicine

Proteomics profiling of serum exosomes from azithromycin-sensitive and resistant mycoplasma pneumoniae infected patients reveals candidate biomarkers for diagnosis

Provisionally accepted
Huifeng  FanHuifeng Fan1Feng  HuangFeng Huang2Chen  ChenChen Chen1Qiaoli  RenQiaoli Ren1Jing  ZhouJing Zhou3Diyuan  YangDiyuan Yang1Gen  LuGen Lu1*
  • 1Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
  • 2The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
  • 3Department of Respiration, Liuzhou Hospital, Guangzhou Women and Children’s Medical Center, Liuzhou Guangxi, China, Liuzhou, China

The final, formatted version of the article will be published soon.

Introduction: Mycoplasma pneumoniae (M. pneumoniae) infections are prevalent among school-age children, and an increasing number of patients are developing resistance to azithromycin (AZM). However, effective biomarkers for diagnosing AZM resistance are currently lacking. This study aimed to identify potential biomarkers for AZM resistance in M. pneumoniae infections by analyzing serum exosomes. Methods:Serum samples were collected from M. pneumoniae-infected patients before and after AZM treatment and were categorized into two groups: responders and non-responders. Serum exosomes were isolated and analyzed using nanoparticle tracking analysis (NTA) and proteomics profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differential protein expression patterns were compared between AZM-sensitive and resistant patients, and potential biomarkers were identified and validated. Results: Distinct exosomal protein expression patterns were observed between AZM-sensitive and resistant patients. The HIF-1 and IL-17 signaling pathways were found to be associated with AZM resistance. Four proteins (KCTD12, LTF, TF, and MPO) were identified as potential biomarkers for distinguishing responders from non-responders. These biomarkers demonstrated over 80% sensitivity and 73.33% specificity in differentiating between the two groups. Conclusion:The study successfully identified four potential biomarkers (KCTD12, LTF, TF, and MPO) for AZM resistance in M. pneumoniae infections. These biomarkers may serve as useful diagnostic tools in clinical settings, aiding in the identification of patients who may not respond to AZM treatment. Future research should focus on validating these biomarkers in larger cohorts and exploring their potential applications in clinical practice.

Keywords: Mycoplasma pneumoniae, azithromycin resistance, Serum exosome, Proteomics profiling, diagnosis

Received: 01 Aug 2025; Accepted: 28 Oct 2025.

Copyright: © 2025 Fan, Huang, Chen, Ren, Zhou, Yang and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Gen Lu, lugen5663330@sina.com

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