Copper ions restore antibacterial activity of tigecycline by regulating photodegradation pathway under light exposure‌

  • Commun Biol. 2026 May 29. doi: 10.1038/s42003-026-10381-y.
Jinjing Xue  #  1 ,  Qianyu Zhou  #  2 ,  Yuanyuan Liu  1 ,  Lin Ma  1 ,  Yonglin Zhou  3  4
Affiliations
  • 1. Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, School of Life Sciences, Ningxia University, Yinchuan, China.
  • 2. State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
  • 3. Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, School of Life Sciences, Ningxia University, Yinchuan, China. [email protected].
  • 4. State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, Jilin, China. [email protected].
  • # Contributed equally.
PMID: 42215682 DOI: 10.1038/s42003-026-10381-y
Abstract

Photodegradation of tetracyclines is a research hotspot due to deactivation and toxic degradation products. We observed that only tigecycline and minocycline, at working concentrations, exhibit a reduction in Antibacterial activity under light exposure. In contrast, Other tetracyclines maintain Antibacterial activity post-degradation. Here we have successfully identified chalcanthite, from the mineral drug resource library. Cu2+ salts with development potential were confirmed to restore the Antibacterial activity of tigecycline under light exposure against all tested Bacterial strains (FIC < 0.5) except for P. aeruginosa. Spectroscopic/Chromatographic characterization combined with quantum chemical calculations elucidated the molecular mechanism by which Cu2+ selectively modulates the photolytic degradation pathway of tigecycline and structural determinants (Protect the dimethylamino group on the D-ring). Multi-omics technologies revealed that Cu2+-mediated (non-antibacterial) inhibition of Bacterial ferric citrate transporter. Animal Infection models demonstrated the therapeutic efficacy of copper gluconate-tigecycline under photic conditions, yielding adjuvants for topical formulations and a scientific foundation for photostable tetracycline-based Antibiotics.

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