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Insights into the antibacterial mechanism of PEGylated nano-bacitracin A against Streptococcus pneumonia: both penicillin-sensitive and penicillin-resistant strains

Authors Hong W, Liu L, Zhang Z, Zhao Y, Zhang D, Liu M

Received 28 June 2018

Accepted for publication 18 September 2018

Published 10 October 2018 Volume 2018:13 Pages 6297—6309

DOI https://doi.org/10.2147/IJN.S178596

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


Wei Hong, Lipeng Liu, Zehui Zhang, Yining Zhao, Dexian Zhang, Mingchun Liu

Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, Liaoning Province 110866, People’s Republic of China

Background: Multidrug-resistant (MDR) Streptococcus pneumonia constitute a major worldwide public health concern.
Materials and methods: In our preliminary study, PEGylated nano-self-assemblies of bacitracin A (PEGylated Nano-BA12K) showed strong antibacterial potency against reference S. pneumonia strain (ATCC 49619). In this study, the possibility of applying PEGylated Nano-BA12K against penicillin-resistant S. pneumonia was further investigated. In addition, the underlying antibacterial mechanism of PEGylated Nano-BA12K against both sensitive and resistant S. pneumonia was also clarified systematically, since S. pneumonia was naturally resistant to its unassembled counterpart bacitracin A (BA).
Results: PEGylated Nano-BA12K showed strong antibacterial potency against 13 clinical isolates of S. pneumonia, including five penicillin-resistant strains. Structural changes, partial collapse, and even lysis of both penicillin-sensitive and penicillin-resistant bacteria were observed after incubation with PEGylated Nano-BA12K via transmission electron microscopy and atomic force microscopy. Thus, the cell wall or/and cell membrane might be the main target of PEGylated Nano-BA12K against S. pneumonia. PEGylated Nano-BA12K exhibited limited effect on the permeabilization and peptidoglycan content of cell wall. Surface pressure measurement suggested that PEGylated Nano-BA12K was much more tensioactive than BA, which was usually translated into a good membranolytic effect, and is helpful to permeabilize the cell membrane and damage membrane integrity, as evidenced by depolarization of the membrane potential, permeabilization of membrane and leakage of calcein from liposomes.
Conclusion: Collectively, great cell membrane permeability and formidable membrane disruption may work together for the strong antibacterial activity of PEGylated Nano-BA12K against S. pneumonia. Taken together, PEGylated Nano-BA12K has excellent potential against both penicillin-sensitive and penicillin-resistant S. pneumonia and might be suitable for the treatment of S. pneumonia infectious diseases.

Keywords: PEGylated Nano-BA12K, multidrug-resistant, Streptococcus pneumonia, penicillin-sensitive and penicillin-resistant

Corrigendum for this paper has been published

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