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The herbal-derived honokiol and magnolol enhances immune response to infection with methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA)

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The emergence of antibiotic resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) reminds us an urgent need to develop a new immune-modulating agent for preventing S. aureus infection. In this study, we found that herbal medicines, honokiol and magnolol, caused a significant cellular immune modulatory effect during S. aureus infection. In mouse macrophages, these compounds drove upregulation of an antioxidant effect in response to S. aureus, resulting in a dampened total cellular reactive oxygen species (ROS) production and decreased production of inflammatory cytokines/chemokines, whereas honokiol induced increased types I and III interferon messenger RNA (mRNA) expression levels in response to MSSA infection. Moreover, the internalization of S. aureus by human alveolar epithelial cells was inhibited by these compounds. Furthermore, honokiol and magnolol treatment promoted a delay in killing during MSSA infection in Caenorhabditis elegans, suggesting antimicrobial function in vivo. In conclusion, honokiol and magnolol may be considered as attractive immune-modulating treatment for S. aureus infection.
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Supplementary material 1
Applied Microbiology and Biotechnology 2
3
The herbal-derived honokiol and magnolol enhances immune response to 4
infection with methicillin-sensitive Staphylococcus aureus (MSSA) and 5
methicillin-resistant S. aureus (MRSA) 6
7
Eun-Jin Choi1, Hyung-Ip Kim2, Ji-Ae Kim2, Seong-Yeop Jeong3, Seok-Jun Son4, Younghoon Kim4*, 8
Ok Sarah Shin2,5* 9
1Asian Pacific Influenza Institute, College of Medicine, Korea University, Seoul, Republic of Korea 10
2Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, Republic of 11
Korea 12
3Microbial Institute for Fermentation Industry (MIFI), Sunchang-gun, Jeollabuk-do 595-804, Korea 13
4BK21 Plus Graduate Program, Department of Animal Science and Institute Agricultural Science & 14
Technology, Chonbuk National University, Jeonju, 561-756, Korea 15
5Department of Microbiology College of Medicine, Korea University, Seoul, Republic of Korea 16
17
18
* Corresponding author: 19
Dr. Younghoon Kim (Assistant Professor) 20
Department of Animal Science and Institute Agricultural Science & Technology, Chonbuk National 21
University 22
567 Baekje-Daero, Deokjin-Gu, Jeonju 561-756, Republic of Korea 23
Tel: 82-63-219-5265, FAX: 82-63-270-2612, E-mail: ykeys2584@jbnu.ac.kr 24
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2
Table S1. Antibacterial activity of honokiol and magnolol against Gram+ bacterium by paper 27
disc method 28
* 0’ indicates no sensitivity or zone of inhibition lower than 8 mm. The data represents average of 29
three independent experiments. 30
Bacterial species
Honokiol
Magnolol
B. subtilis ATCC 6633
17.00 ± 2.000
16.33 ± 1.528
E. faecalis MMH594
17.00 ± 1.000
15.67 ± 0.577
L. monocytogenes ScottA
19.33 ± 2.517
17.67 ± 2.887
S. aureus RN6390 (MSSA)
19.33 ± 1.155
16.67 ± 2.887
S. aureus MW2 (MRSA)
19.67 ± 0.577
17.00 ± 1.000
S. mutans MT8148
18.67 ± 0.577
18.00 ± 0.000
DMSO control
0.000 ± 0.000
Gentamicin
25.667 ± 1.155
31
32
33
3
Table S2. Minimum inhibitory concentration (MIC) of honokiol and magnolol 34
Bacterial species
Honokiol
Magnolol
B. subtilis ATCC 6633
10
10
E. faecalis MMH594
5
5
L. monocytogenes ScottA
10
10
S. aureus RN6390 (MSSA)
2.5
5
S. aureus MW2 (MRSA)
5
5
S. mutans MT8148
5
5
35
36
4
37
38
39
Figure S1. S. aureus killing and biofilm inhibition are enhanced upon treatment with honokiol 40
and magnolol. 41
Chemical structure of honokiol (A) and magnolol (B) is shown. (C) The viability of S. aureus cells 42
was evaluated by counting colony forming units (CFU) after 24 h of incubation in TSB medium at 43
37°C in the absence or presence of 10 µg/mL concentrations of honokiol and magnolol. The data 44
shown is presented as mean ± SD for three independent experiments. *p<0.05 for comparison with 45
the DMSO-treated control. (D) For biofilm formation, crystal violet staining of S. aureus biofilms in 46
the presence or absence of honokiol and magnolol (10 µg/mL) was performed. The amount of crystal 47
violet retained by biofilms was quantitated using optical density measurements (OD 570 nm). Control 48
DMSO-treated samples were normalized to 100% biofilm formation and biofilm formation by 49
honokiol or magnolol-treated samples were compared to the control. The data shown is presented as 50
mean ± SD for three independent experiments. *p<0.05 for comparison with the DMSO-treated 51
control. 52
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