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Synergistic Anti-Staphylococcal Activity Of Niosomal Recombinant Lysostaphin-LL-37

Authors Sadeghi S, Bakhshandeh H, Ahangari Cohan R, Peirovi A, Ehsani P, Norouzian D

Received 8 September 2019

Accepted for publication 7 November 2019

Published 10 December 2019 Volume 2019:14 Pages 9777—9792


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Thomas J. Webster

Somayeh Sadeghi,1,2 Haleh Bakhshandeh,1 Reza Ahangari Cohan,1 Afshin Peirovi,1 Parastoo Ehsani,2 Dariush Norouzian1

1Department of Nano Biotechnology, New Technology Research Group, Pasteur Institute of Iran, Tehran, Iran; 2Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran

Correspondence: Parastoo Ehsani
Department of Molecular Biology, Pasteur Institute of Iran, #69 Pasteur Avenue, Tehran 13164, Iran
Tel + 98 21 64112219
Fax + 98 21 64112803

Dariush Norouzian
Department of Nano Biotechnology, New Technology Research Group, Pasteur Institute of Iran, #69 Pasteur Avenue, Tehran 13164, Iran
Tel + 98 21 64112137
Fax + 98 21 66465132

Purpose: Staphylococcus aureus is the most common persistent pathogen in humans, so development of new formulations to combat pathogen invasion is quite necessary.
Methods: In the current study, for the first time, the synergistic activity of recombinant lysostaphin and LL-37 peptide was studied against S. aureus. Moreover, different niosomal formulations of the peptide and protein were prepared and analyzed in terms of size, shape, zeta potential, and entrapment efficiency. Also, a long-term antibacterial activity of the best niosomal formulation and free forms was measured against S. aureus in vitro.
Results: The optimal niosomal formulation was obtained by mixing the surfactants (span60 and tween60; 2:1 w/w), cholesterol, and dicetylphosphate at a ratio of 47:47:6, respectively. They showed uniform spherical shapes with the size of 565 and 325 nm for lysostaphin and LL-37, respectively. This formulation showed high entrapment efficiency for the peptide, protein, and a slow-release profile over time. Release kinetic was best fitted by Higuchi model indicating a diffusion-based release of the drugs. The lysostaphin/LL-37 niosomal formulation synergistically inhibited growth of S. aureus for up to 72 hours. However, the same amounts of free forms of both anti-microbial agents could not hold the anti-microbial effect and growth was seen in the following 72 hours. Cytotoxicity assay specified that lysostaphin/LL-37 niosomal combination had no deleterious effect on normal fibroblast cells at effective antimicrobial concentrations.
Conclusion: This study indicated that the use of lysostaphin in combination with LL-37, either in niosomal or free forms, synergistically inhibited growth of S. aureus in vitro. In addition, niosomal preparation of antimicrobial agents could provide a long-term protection against bacterial infections.

Keywords: LL-37, lysostaphin, sustained release, synergy, Staphylococcus aureus

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