Oncotarget

Research Papers:

Assessment of antimicrobial and wound healing effects of Brevinin-2Ta against the bacterium Klebsiella pneumoniae in dermally-wounded rats

Siqin Liu, Qilin Long, Yang Xu, Jun Wang, Zhongwei Xu, Lei Wang, Mei Zhou, Yuxin Wu _, Tianbao Chen and Chris Shaw

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Oncotarget. 2017; 8:111369-111385. https://doi.org/10.18632/oncotarget.22797

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Abstract

Siqin Liu1,*, Qilin Long1,*, Yang Xu2, Jun Wang2, Zhongwei Xu3, Lei Wang1, Mei Zhou1, Yuxin Wu1, Tianbao Chen1 and Chris Shaw1

1Natural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, United Kingdom

2Department of General Surgery, The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China

3Center Laboratory of Logistics University of Chinese People’s Armed Police Forces, Tianjin, China

*These authors contributed equally to this work and should be considered as co-first authors

Correspondence to:

Yuxin Wu, email: yuxin.wu@qub.ac.uk

Keywords: AMP; brevinine; inflammation; angiogenesis; Klebsiella pneumoniae

Received: August 13, 2017     Accepted: November 16, 2017     Published: November 30, 2017

ABSTRACT

Antimicrobial peptides (AMPs) are regarded as promising alternatives for antibiotics due to their inherent capacity to prevent microbial drug resistance. Amphibians are rich source of bioactive molecules, which provide numerous AMPs with various structures as drug candidates. Here, we isolated and identified a novel AMP Brevinin-2Ta (B-2Ta) from the skin secretion of the European frog, Pelophylax kl. esculentus. In vitro studies revealed that it showed broad antimicrobial activities against S. aureus, E. coli and C. albicans with low cytotoxicity to erythrocytes. Furthermore, we examined the anti-inflammation effect in vivo by using Klebsiella pneumoniae-infected Sprague-Dawley (SD) rats. The wound closure outcomes revealed that B-2Ta effectively restrained the bacterial infection at a dose of 10 times minimal inhibitory concentration (MIC) during the 14 days of the wound healing process. Ultra-structure analyses showed that B-2Ta caused structural damage to the microorganism, and bacterial culture found that the number of microbes was significantly reduced by the end of treatment. Immunohistochemistry for the inflammatory marker IL-10 and the endothelial cell marker CD31 suggested positive effects on inflammatory status and epithelial migration and angiogenesis following treatment of the infected granulation tissues with B-2Ta. These results exhibited the continuous phase of inflammation reduction and wound healing acceleration in the B-2Ta-modulated re-epithelialisation of K. pneumoniae infected rats. Taken together, these data demonstrated that B-2Ta has great potential to be developed as antibacterial agents in clinic.


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