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Updated: May 22, 2025

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
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Polymyxin B induces pigmentation by upregulating ATG2A-ERK/CREB-MITF-PMEL17 signaling axis

Miao-Qing Zhang1, Zheng-Hao Wang1, Dan-Qing Song1

  • 1Key Laboratory of Biotechnology of Antibiotics, the National Health Commission (NHC), Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Life Sciences
|March 12, 2025
PubMed

Insights

Polymyxin B causes skin hyperpigmentation by disrupting autophagy, leading to melanin precursor accumulation. This study reveals how autophagy proteins regulate melanin synthesis, offering insights into managing this side effect.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Pharmacology

Background:

  • Polymyxin B is a crucial last-resort antibiotic for multidrug-resistant Gram-negative infections.
  • Polymyxin B-induced hyperpigmentation is a significant side effect impacting patient adherence.
  • The mechanism behind polymyxin B-induced pigmentation is not fully understood.

Purpose of the Study:

  • To investigate the link between polymyxin B-induced pigmentation and autophagy.
  • To compare the effects of polymyxin B and polymyxin E on pigmentation pathways.
  • To elucidate the molecular mechanisms of polymyxin B-induced hyperpigmentation.

Main Methods:

  • Utilized zebrafish and melanoma cell models.
  • Performed comparative analysis of polymyxin B and polymyxin E.
  • Conducted RNA sequencing (RNA-seq) to analyze autophagy gene expression.
  • Investigated the role of ATG2A and the LC3B-II/pERK/pCREB pathway.

Main Results:

  • Polymyxin B increased PMEL17 expression and inhibited autophagic degradation, unlike polymyxin E.
  • Polymyxin B upregulated ATG2A expression, promoting MITF and PMEL17 overexpression via the LC3B-II/pERK/pCREB pathway.
  • Evidence suggests autophagosomes may transform into melanosomes, accumulating PMEL17.

Conclusions:

  • Polymyxin B-induced pigmentation is mechanistically linked to autophagy inhibition and impaired degradation of melanin precursors.
  • ATG2A and the LC3B-II/pERK/pCREB pathway are key mediators in this process.
  • Findings contribute to understanding autophagy's role in melanin synthesis and managing antibiotic side effects.
Keywords:
ATG2AAutophagyMelanoma cellsPMEL17PigmentationPolymyxin B

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