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Lactobacillus plantarum USM8613 Aids in Wound Healing and Suppresses Staphylococcus aureus Infection at Wound Sites

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Abstract

This study aimed to elucidate the targets and mechanisms of anti-staphylococcal effects from bioactive metabolites produced by lactic acid bacteria. We aimed to better understand the safety and efficacy of these bioactive metabolites in in vivo systems, typically at topical sites. The cell-free supernatant and protein-rich fraction from Lactobacillus plantarum USM8613 inhibited staphyloxanthin biosynthesis, reduced (p < 0.05) the cell number of Staphylococcus aureus by 106 CFU/mL and reduced biofilm thickness by 55% in S. aureus-infected porcine skins. Genome-wide analysis and gene expression analysis illustrated the production of several plantaricins, especially the plantaricins EF and JK that enhanced the anti-staphylococcal effects of L. plantarum USM8613. In vivo data using rats showed that the protein-rich fraction from L. plantarum USM8613 exerted wound healing properties via direct inhibition of S. aureus and promoted innate immunity, in which the expression of β-defensin was significantly (p < 0.05) upregulated by 3.8-fold. The protein fraction from L. plantarum USM8613 also significantly enhanced (p < 0.05) the production of cytokines and chemokines through various stages of wound recovery. Using ∆atl S. aureus, the protein-rich fraction from L. plantarum USM8613 exerted inhibitory activity via targeting the atl gene in S. aureus. Taken altogether, our present study illustrates the potential of L. plantarum USM8613 in aiding wound healing, suppressing of S. aureus infection at wound sites and promoting host innate immunity.

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Acknowledgements

The Δatl S. aureus strain was kindly provided by Prof. Dr. Hiroshi Ohno from the RIKEN Center for Integrative Medical Sciences (Japan).

Funding

This research was funded by the USM-RIKEN International Centre for Ageing Science (URICAS) grant (1001/PEKIND/870030).

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Authors and Affiliations

  1. School of Industrial Technology, Universiti Sains Malaysia, 11800, Penang, Malaysia

    Jia Sin Ong, Cheng Chung Yong & Min Tze Liong

  2. Laboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan

    Todd D. Taylor

  3. USM-RIKEN International Centre for Ageing Science (URICAS), Universiti Sains Malaysia, 11800, Penang, Malaysia

    Todd D. Taylor, Hiroshi Ohno & Min Tze Liong

  4. Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800, Penang, Malaysia

    Boon Yin Khoo & Sreenivasan Sasidharan

  5. School of Data Sciences, Perdana University, 43400, Selangor, Malaysia

    Sy Bing Choi

  6. Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan

    Hiroshi Ohno

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  1. Jia Sin Ong
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Contributions

Ohno H and Liong MT designed the experiments. JS Ong, Yong CC, Khoo BY, Sasidharan S and Choi SB performed the analyses. Taylor TD, JS Ong, Yong CC, Ohno H and Liong MT wrote the manuscript.

Corresponding authors

Correspondence to Hiroshi Ohno or Min Tze Liong.

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The experimental protocol for treating animals was approved and in accordance with the guidelines recommended by the USM Committee on Animal Care; reference number: USM/Animal Ethics Approval/2012/(81)(433).

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The authors declare that they have no competing interests.

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Ong, J.S., Taylor, T.D., Yong, C.C. et al. Lactobacillus plantarum USM8613 Aids in Wound Healing and Suppresses Staphylococcus aureus Infection at Wound Sites. Probiotics & Antimicro. Prot. 12, 125–137 (2020). https://doi.org/10.1007/s12602-018-9505-9

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