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Applied Microbiology and Biotechnology

, Volume 101, Issue 11, pp 4691–4700 | Cite as

Rapid killing of bacteria by a new type of photosensitizer

  • Yaxin Zhang
  • Ke Zheng
  • Zhuo Chen
  • Jincan Chen
  • Ping Hu
  • Linrong Cai
  • Zafar Iqbal
  • Mingdong Huang
Applied microbial and cell physiology

Abstract

Photodynamic antimicrobial chemotherapy (PACT) uses non-traditional mechanisms (free radicals) and is a highly advocated method with promise of inactivating drug-resistance bacteria for local infections. However, there is no related drug used in clinical practice yet. Therefore, new photosensitizers for PACT are under active development. Here, we report the synthesis of a series of photosensitizers with variable positive charges (ZnPc(TAP)4 n+, n = 0, 4, 8, 12) and their inactivation against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The binding kinetics of ZnPc(TAP)4 n+ to bacteria were measured by flow cytometer. Reactive oxygen species (ROS) generation mechanism of the photosensitizers was studied. The toxicity of these compounds to human blood cells was also evaluated. These compounds showed negligible toxicity against human erythocytes but potent bactericidal effects. The compound with 8 positive charges, ZnPc(TAP)4 8+, turned out to have the strongest antibacterial effect among this series of compounds, giving IC50 value of 59 nM at a light dosage of 5 J/cm2 toward E. coli. For a multi-resistant E. coli strain, ZnPc(TAP)4 8+ decreased the bacteria load by 1000-fold at a concentration of 1 μM. Interestingly, ZnPc(TAP)4 12+, instead of ZnPc(TAP)4 8+, exhibited the highest amount of binding to bacteria. Flow cytometry studies showed that all PSs have fast binding onto bacteria, reaching saturated binding within 5 min. Mechanistically, ZnPc(TAP)4 12+ generated ROS primarily via Type I mechanism, while ZnPc(TAP)4 4+ or ZnPc(TAP)4 8+ created ROS by both type I and type II mechanisms. ZnPc(TAP)4 n+ are highly potent, rapid-acting and non-toxic photosensitizers capable of inactivating bacteria.

Keywords

Photodynamic antimicrobial chemotherapy (PACT) Mechanistic study ROS measurement Phthalocyanine Photosensitizer 

Notes

Acknowledgements

We thank The Second Municipal Hospital of Fuzhou for providing us the strain of multi-resistant E. coli. This work was supported by grants from National Natural Science Foundation of China (81171634), Natural Science Foundation of Fujian Province (2013J01066).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Funding

This work is supported by grants from Natural Science Foundation of China (31,370,737, 31,400,637, 31,570,745, 31,670,739, 81,572,944, and U1405229), and the CAS/SAFEA International Partnership Program for Creative Research Teams.

Supplementary material

253_2017_8133_MOESM1_ESM.pdf (498 kb)
ESM 1 (PDF 497 kb).

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Yaxin Zhang
    • 1
  • Ke Zheng
    • 2
  • Zhuo Chen
    • 1
  • Jincan Chen
    • 1
  • Ping Hu
    • 1
  • Linrong Cai
    • 1
  • Zafar Iqbal
    • 1
    • 3
  • Mingdong Huang
    • 1
    • 4
  1. 1.State Key Laboratory of Structural ChemistryFujian Institute of Research on the Structure of Matter, Chinese Academy of SciencesFuzhouChina
  2. 2.College of Chemical EngineeringQingdao University of Science and TechnologyQingdaoChina
  3. 3.Department of ChemistryCOMSATS Institute of Information Technology (CIIT)AbbottabadPakistan
  4. 4.College of ChemistryFuzhou UniversityFuzhouChina

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