皮膚表皮葡萄球菌作為電力活性菌以抑制痤瘡丙酸桿菌

以作者查詢圖書館館藏

、以作者查詢臺灣博碩士

、以作者查詢全國書目

、勘誤回報

、線上人數：7

、訪客IP：18.191.211.66

姓名

施芯蒂(Shinta Marito) 查詢紙本館藏

畢業系所

生醫科學與工程學系

論文名稱

皮膚表皮葡萄球菌作為電力活性菌以抑制痤瘡丙酸桿菌
(Skin Staphyloccus epidermidis as an electroactive microbe against Cutibacterium acnes)

相關論文

★ Intelligent nature-derived coordinative hydrogel incorporated with HRP as dressing for infected wounds	★ 表皮葡萄球菌在人類皮膚微生物總體對皮膚訊號與腦波訊號影響
★ 土壤微生物組體研究：藉由內生細菌誘導之高GABA含量水稻增加神經肽Y以及減輕小鼠焦慮	★ Fermentation of Leuconostoc mesenteroides reduces abdominal fat accumulation in high-fat diet mice
★ 選擇性發酵引發劑（SFI）觸發表皮葡萄球菌發酵以緩解UV-B誘導的自由基生成	★ Identify and characterize the fermenting and electrogenic skin bacteria using selective prebiotics
★ 有益微生物的真菌學和細菌學研究：在農業和人類健康中的應用	★ 人體皮膚致電微生物組通過調節鐵和自由基來減輕紫外線B引起的皮膚損傷。
★ 微生物組中的細菌作為治療人類疾病的生物療法	★ 鼠李糖乳桿菌作為益生菌對抗 SARS-CoV-2 膜糖蛋白誘導的炎症
★ Flavin mononucleotide-based electricity production by Staphylococcus epidermidis alleviates SARS-CoV-2- Nucleocapsid Phosphoprotein-induced IL-6 expression	★ Profiling the Age-related Microbiome via Detection of Antibodies to Gut Bacteria
★ 基於PEG的益生元影響皮膚細菌和皮膚電的發酵	★ 液化澱粉芽孢桿菌用於產生富含GABA的水稻以增強小鼠皮膚中膠原蛋白表達的可能機制
★ 基於PEG的益生元對痤瘡痤瘡桿菌的表皮葡萄球菌發酵和電的研究	★ 設計開發全氟碳複合奈米藥物載體對體表微生物多效抑菌功能之研究

檔案

[Endnote RIS 格式]

[Bibtex 格式]

[相關文章]

[文章引用]

[完整記錄]

[館藏目錄]

至系統瀏覽論文 ( 永不開放)

摘要(中)

Abstract in Chinese
抗生素用於青春痘治療或是直接透過皮膚益生菌──表皮葡萄球菌 (Staphylococcus
epidermidis, S. epidermidis) 來對抗與青春痘相關的細菌 ── 痤瘡丙酸桿菌
(Cutibacterium acnes, C. acnes)，可能會導致皮膚菌叢失衡的現象。透過各式樣的
碳元，可以引出表皮葡萄球菌不同的益生菌活性。以含豐富碳元的聚乙二醇-8 月桂酸
酯為例，它可以選擇性讓 S. epidermidis 發酵而不使 C. acnes 發酵，而藉由聚乙二醇
-8 月桂酸酯發酵的 S. epidermidis 可以明顯減少 C. acnes 的生長，同時在小鼠實驗
上，亦可以抑制 C. acnes 誘導的巨噬細胞炎性蛋白 2(macrophage-inflammatory
protein 2, MIP-2)生成。除此之外，發酵產物亦可以增強市面上販售的抗生素抗菌的
功效，在常見的克林黴素(Clindamycin)上，以低劑用量搭配發酵產物即可抑制 C.
acnes 形成菌落同時減少 MIP-2 生成。聚乙二醇-8 月桂酸酯在 S. epidermidis 發酵上
扮演重要的佐劑，同時亦可以幫助 Clindamycin 抗菌的功能。這樣同時具有減少抗生
素用量以避免副作用及維持皮膚菌叢平衡的治療方式，在治療青春痘的應用上可以譜
出嶄新的頁面。我們亦透過 FerroZine 試劑變化來鑑定了 S. epidermidis 為產電菌株，
抑制親環蛋白 A 可以大幅減弱微生物燃料電池的電壓變化。聚乙二醇-8 月桂酸酯作為
電子給體讓 S. epidermidis 產生電性，或是調和親環蛋白來誘導出電流，藉此產生抗
菌功能。S. epidermidis 產生的電性也能即時授與青春痘患部的先天免疫系統，這樣
從細胞內外間的電子轉移可以作為選擇性標的病源細菌的替代方案

摘要(英)

Abstract in English
Antibiotics without selectivity for acne treatment or probiotic treatment by direct application of
live Staphylococcus epidermidis (S. epidermidis), to fight Cutibacterium acnes (C. acnes),
associated with inflammatory acne vulgaris, may result in microbial dysbiosis in the human
microbiome. The probiotic activity of skin Staphylococcus epidermidis (S. epidermidis)
bacteria can elicit diverse biological functions via the fermentation of various carbon sources.
By using polyethylene glycol (PEG)-8 Laurate, a carbon-rich molecule, can selectively induce
the fermentation of S. epidermidis, not Cutibacterium acnes (C. acnes), a bacterium associated
with acne vulgaris. The PEG-8 Laurate fermentation of S. epidermidis remarkably diminished
the growth of C. acnes and the C. acnes-induced production of pro-inflammatory macrophage-
inflammatory protein 2 (MIP-2) cytokines in mice. Fermentation media enhanced the anti-C.
acnes activity of a low dose (0.1%) clindamycin, a prescription antibiotic commonly used to
treat acne vulgaris, in terms of the suppression of C. acnes colonization and MIP-2 production.
The PEG-8 Laurate fermentation of S. epidermidis displayed the adjuvant effect on promoting
the efficacy of low-dose clindamycin against C. acnes. Targeting C. acnes by lowering the
required doses of antibiotics may avoid the risk of creating drug-resistant C. acnes and maintain
the bacterial homeostasis in the skin microbiome, leading to a novel modality for the antibiotic
treatment of acne vulgaris.
We have also identified the S. epidermidis ATCC 12228 as an electrogenic bacterial strain using
a ferrozine investigation. Transferring electrons from the cytosol to the exterior of the cell via
the EET process represents an alternative strategy that may selectively target pathogenic
bacteria. The fermentation of PEG – 8 Laurate produced by S. epidermidis may generate
electricity through PEG-8 Laurate as an electron donor or mediate cyclophilin A to elicit an
electrical current that has anti-C. acnes effects. Electricity generated by S. epidermidis may
confer immediate innate immunity in acne lesions to rein in the overgrowth of C. acnes at the
ii

onset of acne vulgaris. Inhibition of Cyclophilin A of S. epidermidis significantly reduced the
bacterial electricity measured in a fuel cell by voltage changes (MFC)

論文目次

Table of contents
Contents

Abstact in Chinese ...................................................................................................................... i
Abstact in English ...................................................................................................................... ii
List of Figure ............................................................................................................................ vi
Abbreviations .......................................................................................................................... viii
Chapter 1 - Literature review ..................................................................................................... 1
1.1. The skin microbiome ............................................................................................................. 1
1.2. Acne vulgaris .......................................................................................................................... 2
1.3. Stapyloccus epidermidis ....................................................................................................... 2
1.4. Short Chain Fatty Acid (SCFA) ......................................................................................... 3
1.5. S. epidermidis inhibit C. acnes ............................................................................................ 3
1.6. Extracelluler Electron Transfer (EET) .............................................................................. 4
1.7. Microbial Fuel Cell (MFC) ................................................................................................... 5
Chapter 2 – PEG-8 Laurate Fermentation of Staphylococcus epidermidis Reduces the
Required Dose of Clindamycin Against Cutibacterium acnes .................................................. 7
2.1. Introduction ............................................................................................................................ 7
2.2. Materials and Methods ......................................................................................................... 9
2.2.1. Bacterial Culture ........................................................................................................... 9
2.2.2. Fermentation of Bacteria ............................................................................................. 9
2.2.3. PEG-8 Laurate Fermentation of S. epidermidis Against C. acnes In Vivo ......... 10
2.2.4. Bacterial Loads in Mouse Ears ................................................................................. 10
2.2.5. An Overlay Assay ....................................................................................................... 10
2.2.6. ELISA ........................................................................................................................... 11
2.2.7. Statistical Analysis ...................................................................................................... 11
2.3. Results ................................................................................................................................... 12
2.3.1. PEG -8 Laurate as a Selective Carbon Source for Fermentation of S. epidermidis

....................................................................................................................................... 12
2.3.2. PEG-8 Laurate Fermentation of S. epidermidis Against C. acnes In Vivo ....... 13
2.3.3. Reduction of the Effective Dose of Clindamycin Against C. acnes by

Fermentation Media .................................................................................................. 14
2.3.4. Enhancement of Low Dose of Clindamycin for Inhibition of the Growth of C.

acnes Colonies by PEG-8 Laurate Fermentation .................................................. 16
iv

2.4. Discussion ........................................................................................................................... 17
Chapter 3 – Electricity –producing Staphyloccus epidermidis Counteracts Cutibacterium

acnes .............................................................................................................. 21
3.1. Introduction ......................................................................................................................... 22
3.2. Material and Methods ......................................................................................................... 23
3.2.1. Bacterial culture .......................................................................................................... 23
3.2.2. Fermentation of bacteria ............................................................................................. 23
3.2.3. Detection of bacterial electricity ............................................................................... 24
3.2.4. The interference of S. epidermidis with the growth of C. acnes in vitro ............ 25
3.2.5. High- performance liquid chromatography (HPLC) analysis ............................... 25
3.2.6. Ferrozine assays ......................................................................................................... 26
3.2.7. S. epidermidis against C. acnes in vivo ................................................................... 26
3.2.8. Statistical analysis ..................................................................................................... 27
3.3. Results .................................................................................................................................. 28
3.3.1. PEG-8 Laurate induces electricity production by S. epidermidis ...................... 28
3.3.2. Electrogenic S. epidermidis impedes the growth of C.acnes .............................. 29
3.3.3. The blockade of electricity production attenuates the suppressive effect of S.

epidermidis against C. acnes in vitro ..................................................................... 32
3.3.4. Production of electrons by S. epidermidis is detected by ferrozine assays and

induces the lysis of C. acnes .................................................................................... 34
3.3.5. Electron production mediated by cyclophilin A in S. epidermidis attenuates

viability of C. acnes in vivo ...................................................................................... 35
3.4. Disscusion ............................................................................................................................ 37
Chapter 4 – Conclusion and outlooks ..................................................................................... 42

References ............................................................................................................... 44

Appendix ............................................................................................................... 53

參考文獻

References
1.
Huttenhower, C.; Gevers, D.; Knight, R.; Abubucker, S.; Badger, J. H.; Chinwalla, A.
T.; Creasy, H. H.; Earl, A. M.; FitzGerald, M. G.; Fulton, R. S., Structure, function and
diversity of the healthy human microbiome. nature 2012, 486, (7402), 207.
2.
Grice, E. A.; Segre, J. A. J. N. r. m., The skin microbiome. 2011, 9, (4), 244-253.
3.
Doré, J.; Blottière, H., The influence of diet on the gut microbiota and its consequences
for health. Current Opinion in Biotechnology 2015, 32, 195-199.
4.
Oh, J.; Byrd, A. L.; Deming, C.; Conlan, S.; Barnabas, B.; Blakesley, R.; Bouffard, G.;
Brooks, S.; Coleman, H.; Dekhtyar, M., Biogeography and individuality shape function
in the human skin metagenome. Nature 2014, 514, (7520), 59.
5.
Oh, J.; Byrd, A. L.; Park, M.; Kong, H. H.; Segre, J. A.; Program, N. C. S., Temporal
stability of the human skin microbiome. Cell 2016, 165, (4), 854-866.
6.
Flores, G. E.; Caporaso, J. G.; Henley, J. B.; Rideout, J. R.; Domogala, D.; Chase, J.;
Leff, J. W.; Vázquez-Baeza, Y.; Gonzalez, A.; Knight, R., Temporal variability is a
personalized feature of the human microbiome. Genome biology 2014, 15, (12), 531.
7.
Perez, G. I. P.; Gao, Z.; Jourdain, R.; Ramirez, J.; Gany, F.; Clavaud, C.; Demaude, J.;
Breton, L.; Blaser, M. J., Body site is a more determinant factor than human population
diversity in the healthy skin microbiome. PLoS One 2016, 11, (4), e0151990.
8.
Troccaz, M.; Gaïa, N.; Beccucci, S.; Schrenzel, J.; Cayeux, I.; Starkenmann, C.;
Lazarevic, V., Mapping axillary microbiota responsible for body odours using a cultureindependent
approach.
Microbiome
2015,
3,
(1), 3.

9.
Byrd, A. L.; Belkaid, Y.; Segre, J. A., The human skin microbiome. Nature Reviews
Microbiology 2018, 16, (3), 143.
10. Bojar, R. A.; Holland, K. T., Acne and Propionibacterium acnes. Clinics in dermatology
2004, 22, (5), 375-379.
11. Liu, J.; Yan, R.; Zhong, Q.; Ngo, S.; Bangayan, N. J.; Nguyen, L.; Lui, T.; Liu, M.; Erfe,
M. C.; Craft, N., The diversity and host interactions of Propionibacterium acnes
bacteriophages on human skin. The ISME journal 2015, 9, (9), 2078.
12. Kanwar, I. L.; Haider, T.; Kumari, A.; Dubey, S.; Jain, P.; Soni, V., Models for acne: A
comprehensive study. Drug discoveries & therapeutics 2018, 12, (6), 329-340.
13. Dreno, B.; Gollnick, H.; Kang, S.; Thiboutot, D.; Bettoli, V.; Torres, V.; Leyden, J.;
Acne, G. A. t. I. O. i., Understanding innate immunity and inflammation in acne:
implications for management. Journal of the European Academy of Dermatology and
Venereology 2015, 29, 3-11.
14. Mays, R. M.; Gordon, R. A.; Wilson, J. M.; Silapunt, S., New antibiotic therapies for
acne and rosacea. Dermatologic therapy 2012, 25, (1), 23-37.
15. Katsambas, A. D.; Stefanaki, C.; Cunliffe, W. J., Guidelines for treating acne. Clinics
in dermatology 2004, 22, (5), 439-444.
16. Zaenglein, A. L.; Pathy, A. L.; Schlosser, B. J.; Alikhan, A.; Baldwin, H. E.; Berson, D.
S.; Bowe, W. P.; Graber, E. M.; Harper, J. C.; Kang, S., Guidelines of care for the
management of acne vulgaris. Journal of the American Academy of Dermatology 2016,
74, (5), 945-973. e33.
17. Hull, P. R.; D’Arcy, C., Isotretinoin use and subsequent depression and suicide.
American journal of clinical dermatology 2003, 4, (7), 493-505.
18. Wang, Y.; Zhang, L.; Yu, J.; Huang, S.; Wang, Z.; Chun, K. A.; Lee, T. L.; Chen, Y.T.;
Gallo,
R.
L.;
Huang,
C.-M.,
A
Co-Drug
of
Butyric
Acid
Derived
from
Fermentation

Metabolites
of
the
Human
Skin
Microbiome
Stimulates
Adipogenic
Differentiation
of

Adipose-Derived

Stem Cells: Implications in Tissue Augmentation. Journal of
Investigative Dermatology 2017, 137, (1), 46-56.
19. Wang, Y.; Kuo, S.; Shu, M.; Yu, J.; Huang, S.; Dai, A.; Two, A.; Gallo, R. L.; Huang,
C.-M., Staphylococcus epidermidis in the human skin microbiome mediates fermentation to inhibit the growth of Propionibacterium acnes: implications of probiotics in acne vulgaris. Applied microbiology and biotechnology 2014, 98, (1), 411-
424.
20. Christensen, G. J.; Scholz, C. F.; Enghild, J.; Rohde, H.; Kilian, M.; Thürmer, A.; Brzuszkiewicz, E.; Lomholt, H. B.; Brüggemann, H., Antagonism between Staphylococcus epidermidis and Propionibacterium acnes and its genomic basis. BMC genomics 2016, 17, (1), 152.
21. Pathak, R.; Kasama, N.; Kumar, R.; Gautman, H., Staphylococcus epidermidis in human skin microbiome associated with acne: a cause of disease or defence. Res J Biotechnol 2013, 8, 78-82.
22. Wang, Y.; Kao, M.-S.; Yu, J.; Huang, S.; Marito, S.; Gallo, R.; Huang, C.-M., A precision microbiome approach using sucrose for selective augmentation of Staphylococcus epidermidis fermentation against Propionibacterium acnes. International journal of molecular sciences 2016, 17, (11), 1870.
23. Light, S. H.; Su, L.; Rivera-Lugo, R.; Cornejo, J. A.; Louie, A.; Iavarone, A. T.; Ajo- Franklin, C. M.; Portnoy, D. A., A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria. Nature 2018, 562, (7725), 140-144.
24. Wang, W.; Du, Y.; Yang, S.; Du, X.; Li, M.; Lin, B.; Zhou, J.; Lin, L.; Song, Y.; Li, J.
J. A. c., Bacterial extracellular electron transfer occurs in mammalian gut. 2019, 91, (19), 12138-12141.
25. Light, S. H.; Su, L.; Rivera-Lugo, R.; Cornejo, J. A.; Louie, A.; Iavarone, A. T.; Ajo- Franklin, C. M.; Portnoy, D. A. J. N., A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria. 2018, 562, (7725), 140-144.
26. Liu, H.; Cheng, S.; Logan, B. E., Production of electricity from acetate or butyrate using a single-chamber microbial fuel cell. Environmental science & technology 2005, 39, (2),
658-662.
27. Grice, E. A.; Segre, J. A., The skin microbiome. Nature Reviews Microbiology 2011, 9, (4), 244.
28. Levy, M.; Kolodziejczyk, A. A.; Thaiss, C. A.; Elinav, E., Dysbiosis and the immune system. Nature Reviews Immunology 2017, 17, (4), 219.
29. Johnson, M. E.; Franks, J. M.; Cai, G.; Mehta, B. K.; Wood, T. A.; Archambault, K.; Pioli, P. A.; Simms, R. W.; Orzechowski, N.; Arron, S., Microbiome dysbiosis is associated with disease duration and increased inflammatory gene expression in systemic sclerosis skin. Arthritis research & therapy 2019, 21, (1), 49.
30. Dudley, R., Ethanol, fruit ripening, and the historical origins of human alcoholism in primate frugivory. Integrative and comparative biology 2004, 44, (4), 315-323.
31. Iwase, T.; Uehara, Y.; Shinji, H.; Tajima, A.; Seo, H.; Takada, K.; Agata, T.; Mizunoe, Y., Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 2010, 465, (7296), 346.
32. Lai, Y.; Di Nardo, A.; Nakatsuji, T.; Leichtle, A.; Yang, Y.; Cogen, A. L.; Wu, Z.-R.; Hooper, L. V.; Schmidt, R. R.; Von Aulock, S., Commensal bacteria regulate Toll-like receptor 3–dependent inflammation after skin injury. Nature medicine 2009, 15, (12),
1377.
33. Otto, M., Staphylococcus epidermidis—the′accidental′pathogen. Nature reviews microbiology 2009, 7, (8), 555.
34. Yang, A.-J.; Marito, S.; Yang, J.-J.; Keshari, S.; Chew, C.-H.; Chen, C.-C.; Huang, C.- M., A Microtube Array Membrane (MTAM) Encapsulated Live Fermenting

45
Staphylococcus epidermidis as a Skin Probiotic Patch against Cutibacterium acnes.
International journal of molecular sciences 2019, 20, (1), 14.
35. Fitz-Gibbon, S.; Tomida, S.; Chiu, B.-H.; Nguyen, L.; Du, C.; Liu, M.; Elashoff, D.; Erfe, M. C.; Loncaric, A.; Kim, J. J. J. o. i. d., Propionibacterium acnes strain populations in the human skin microbiome associated with acne. 2013, 133, (9), 2152-
2160.
36. Kao, M. S.; Huang, S.; Chang, W. L.; Hsieh, M. F.; Huang, C. J.; Gallo, R. L.; Huang, C. M., Microbiome precision editing: Using PEG as a selective fermentation initiator against methicillin‐resistant Staphylococcus aureus. Biotechnology journal 2017, 12, (4).
37. Schmidt, N. W.; Agak, G. W.; Deshayes, S.; Yu, Y.; Blacker, A.; Champer, J.; Xian, W.; Kasko, A. M.; Kim, J.; Wong, G. C., Pentobra: a potent antibiotic with multiple layers of selective antimicrobial mechanisms against Propionibacterium acnes. Journal of Investigative Dermatology 2015, 135, (6), 1581-1589.
38. Keshari, S.; Kumar, M.; Balasubramaniam, A.; Chang, T.-W.; Tong, Y.; Huang, C.-M., Prospects of acne vaccines targeting secreted virulence factors of Cutibacterium acnes. Expert review of vaccines 2019, 18, (5), 433-437.
39. Humphrey, S., Antibiotic resistance in acne treatment. Skin Therapy Lett 2012, 17, (9),
1-3.
40. Williams, H. C.; Dellavalle, R. P.; Garner, S., Acne vulgaris. The Lancet 2012, 379, (9813), 361-372.
41. Eady, E.; Gloor, M.; Leyden, J., Propionibacterium acnes resistance: a worldwide problem. Dermatology 2003, 206, (1), 54-56.
42. Ross, J.; Snelling, A.; Carnegie, E.; Coates, P.; Cunliffe, W.; Bettoli, V.; Tosti, G.; Katsambas, A.; Galvan Perez Del Pulgar, J.; Rollman, O., Antibiotic‐resistant acne: lessons from Europe. British journal of Dermatology 2003, 148, (3), 467-478.
43. EADY, E. A.; Cove, J.; Holland, K.; Cunliffe, W., Erythromycin resistant propionibacteria in antibiotic treated acne patients: association with therapeutic failure. British Journal of Dermatology 1989, 121, (1), 51-57.
44. Patel, M.; Bowe, W. P.; Heughebaert, C.; Shalita, A. R., The development of antimicrobial resistance due to the antibiotic treatment of acne vulgaris: a review. Journal of drugs in dermatology: JDD 2010, 9, (6), 655-664.
45. Wright, G. D., Antibiotic adjuvants: rescuing antibiotics from resistance. Trends in microbiology 2016, 24, (11), 862-871.
46. Fruijtier, C., Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products. Toxicology 2005, 214, 1-38.
47. Jang, H.-J.; Shin, C. Y.; Kim, K.-B., Safety Evaluation of Polyethylene Glycol (PEG) Compounds for Cosmetic Use. Toxicol Res 2015, 31, (2), 105-136.
48. Yang, Q.; Lai, S. K., Anti-PEG immunity: emergence, characteristics, and unaddressed questions. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2015, 7, (5), 655-77.
49. Liu, Y.; Balachandran, Y. L.; Li, D.; Shao, Y.; Jiang, X., Polyvinylpyrrolidone– Poly(ethylene glycol) Modified Silver Nanorods Can Be a Safe, Noncarrier Adjuvant for HIV Vaccine. ACS Nano 2016, 10, (3), 3589-3596.
50. Wang, J.; Lu, L.; Song, H.; Yang, Y.; Ma, Y., [Effect of polyethylene glycol as adjuvant on hepatitis B virus DNA vaccine in vitro]. Wei Sheng Wu Xue Bao 2010, 50, (7), 949-
54.
51. Karadag, A. S.; Aslan Kayıran, M.; Wu, C. Y.; Chen, W.; Parish, L. C., Antibiotic resistance in acne: changes, consequences and concerns. Journal of the European Academy of Dermatology and Venereology 2020.

46
52. Soares, D. N.; Antonio, A. G.; Iorio, N. L. P.; Pierro, V. S. d. S.; Santos, K. R. N. d.;
Maia, L. C., Does the presence of sucrose in pediatric antibiotics influence the enamel mineral loss and the Streptococcus mutans counts in dental biofilm? Brazilian dental journal 2015, 26, (3), 249-257.
53. Paul, M.; Carmeli, Y.; Durante-Mangoni, E.; Mouton, J. W.; Tacconelli, E.; Theuretzbacher, U.; Mussini, C.; Leibovici, L., Combination therapy for carbapenem- resistant Gram-negative bacteria. Journal of Antimicrobial Chemotherapy 2014, 69, (9),
2305-2309.
54. Robbins, G. B.; Lewis, K. H., Fermentation of sugar acids by bacteria. Journal of bacteriology 1940, 39, (4), 399.
55. Wang, Y.; Kao, M.-S.; Yu, J.; Huang, S.; Marito, S.; Gallo, R. L.; Huang, C.-M., A precision microbiome approach using sucrose for selective augmentation of Staphylococcus epidermidis fermentation against Propionibacterium acnes. International journal of molecular sciences 2016, 17, (11), 1870.
56. Nakatsuji, T.; Kao, M. C.; Fang, J.-Y.; Zouboulis, C. C.; Zhang, L.; Gallo, R. L.; Huang, C.-M., Antimicrobial property of lauric acid against Propionibacterium acnes: its therapeutic potential for inflammatory acne vulgaris. Journal of investigative dermatology 2009, 129, (10), 2480-2488.
57. Melander, R. J.; Melander, C., The Challenge of Overcoming Antibiotic Resistance: An
Adjuvant Approach? ACS Infect Dis 2017, 3, (8), 559-563.
58. Papp-Wallace, K. M.; Bonomo, R. A., New beta-Lactamase Inhibitors in the Clinic.
Infect Dis Clin North Am 2016, 30, (2), 441-464.
59. Drawz, S. M.; Bonomo, R. A., Three decades of beta-lactamase inhibitors. Clin
Microbiol Rev 2010, 23, (1), 160-201.
60. Bush, K., A resurgence of beta-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens. Int J Antimicrob Agents 2015, 46, (5),
483-93.
61. Thompson, R. J.; Bobay, B. G.; Stowe, S. D.; Olson, A. L.; Peng, L.; Su, Z.; Actis, L.
A.; Melander, C.; Cavanagh, J., Identification of BfmR, a response regulator involved in biofilm development, as a target for a 2-Aminoimidazole-based antibiofilm agent. Biochemistry 2012, 51, (49), 9776-8.
62. Cox, G.; Koteva, K.; Wright, G. D., An unusual class of anthracyclines potentiate Gram- positive antibiotics in intrinsically resistant Gram-negative bacteria. Journal of Antimicrobial Chemotherapy 2014, 69, (7), 1844-1855.
63. Li, X.; Jia, Y.; Wang, S.; Meng, T.; Zhu, M., Identification of Genes and Pathways
Associated with Acne Using Integrated Bioinformatics Methods. Dermatology 2019,
235, (6), 445-455.
64. Kelhala, H. L.; Palatsi, R.; Fyhrquist, N.; Lehtimaki, S.; Vayrynen, J. P.; Kallioinen, M.; Kubin, M. E.; Greco, D.; Tasanen, K.; Alenius, H.; Bertino, B.; Carlavan, I.; Mehul, B.; Deret, S.; Reiniche, P.; Martel, P.; Marty, C.; Blume-Peytavi, U.; Voegel, J. J.; Lauerma, A., IL-17/Th17 pathway is activated in acne lesions. PLoS One 2014, 9, (8), e105238.
65. Nakatsuji, T.; Shi, Y.; Zhu, W.; Huang, C. P.; Chen, Y. R.; Lee, D. Y.; Smith, J. W.; Zouboulis, C. C.; Gallo, R. L.; Huang, C. M., Bioengineering a humanized acne microenvironment model: proteomics analysis of host responses to Propionibacterium acnes infection in vivo. Proteomics 2008, 8, (16), 3406-15.
66. Achermann, Y.; Goldstein, E. J.; Coenye, T.; Shirtliff, M. E., Propionibacterium acnes: from commensal to opportunistic biofilm-associated implant pathogen. Clin Microbiol Rev 2014, 27, (3), 419-40.
67. Itakura, M.; Tokuda, A.; Kimura, H.; Nagai, S.; Yoneyama, H.; Onai, N.; Ishikawa, S.; Kuriyama, T.; Matsushima, K., Blockade of Secondary Lymphoid Tissue Chemokine

47
Exacerbates <em>Propionibacterium acnes-</em>Induced Acute Lung
Inflammation. The Journal of Immunology 2001, 166, (3), 2071.
68. Dumont-Wallon, G.; Moyse, D.; Blouin, E.; Dreno, B., Bacterial resistance in French acne patients. Int J Dermatol 2010, 49, (3), 283-8.
69. Leyden, J.; Levy, S., The development of antibiotic resistance in Propionibacterium acnes. Cutis 2001, 67, (2 Suppl), 21-4.
70. Smieja, M., Current indications for the use of clindamycin: A critical review. Canadian
Journal of Infectious Diseases and Medical Microbiology 1998, 9, (1), 22-28.
71. Dréno, B.; Pécastaings, S.; Corvec, S.; Veraldi, S.; Khammari, A.; Roques, C., Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest updates. Journal of the European Academy of Dermatology and Venereology
2018, 32, 5-14.
72. Levy, M.; Kolodziejczyk, A. A.; Thaiss, C. A.; Elinav, E., Dysbiosis and the immune system. Nat Rev Immunol 2017, 17, (4), 219-232.
73. Shi, B.; Bangayan, N. J.; Curd, E.; Taylor, P. A.; Gallo, R. L.; Leung, D. Y. M.; Li, H., The skin microbiome is different in pediatric versus adult atopic dermatitis. J Allergy Clin Immunol 2016, 138, (4), 1233-1236.
74. Gao, Z.; Tseng, C. H.; Strober, B. E.; Pei, Z.; Blaser, M. J., Substantial alterations of the cutaneous bacterial biota in psoriatic lesions. PLoS One 2008, 3, (7), e2719.
75. Kong, H. H.; Oh, J.; Deming, C.; Conlan, S.; Grice, E. A.; Beatson, M. A.; Nomicos, E.; Polley, E. C.; Komarow, H. D.; Program, N. C. S.; Murray, P. R.; Turner, M. L.; Segre, J. A., Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res 2012, 22, (5), 850-9.
76. Kanwar, I.; Haider, T.; Kumari, A.; Dubey, S.; Jain, P.; Soni, V., Models for acne: A
comprehensive study. Drug Discoveries & Therapeutics 2018, 12, 329-340.
77. Finke, N.; Vandieken, V.; Jørgensen, B. B., Acetate, lactate, propionate, and isobutyrate as electron donors for iron and sulfate reduction in Arctic marine sediments, Svalbard. FEMS Microbiology Ecology 2007, 59, (1), 10-22.
78. Chen, C.; Shen, Y.; An, D.; Voordouw, G., Use of acetate, propionate, and butyrate for reduction of nitrate and sulfate and methanogenesis in microcosms and bioreactors simulating an oil reservoir. Appl. Environ. Microbiol. 2017, 83, (7), e02983-16.
79. Sorokin, D. Y.; Detkova, E.; Muyzer, G., Propionate and butyrate dependent bacterial sulfate reduction at extremely haloalkaline conditions and description of Desulfobotulus alkaliphilus sp. nov. Extremophiles 2010, 14, (1), 71-77.
80. Pankratova, G.; Hederstedt, L.; Gorton, L., Extracellular electron transfer features of
Gram-positive bacteria. Analytica chimica acta 2019, 1076, 32-47.
81. Xayarath, B.; Alonzo III, F.; Freitag, N. E., Identification of a peptide-pheromone that enhances Listeria monocytogenes escape from host cell vacuoles. PLoS pathogens 2015,
11, (3).
82. Matsuda, S.; Liu, H.; Kato, S.; Hashimoto, K.; Nakanishi, S., Negative faradaic resistance in extracellular electron transfer by anode-respiring Geobacter sulfurreducens cells. Environmental science & technology 2011, 45, (23), 10163-10169.
83. Pankratova, G.; Leech, D. n.; Gorton, L.; Hederstedt, L., Extracellular electron transfer by the Gram-positive bacterium Enterococcus faecalis. Biochemistry 2018, 57, (30),
4597-4603.
84. Light, S. H.; Su, L.; Rivera-Lugo, R.; Cornejo, J. A.; Louie, A.; Iavarone, A. T.; Ajo- Franklin, C. M.; Portnoy, D. A., A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria. Nature 2018, 562, (7725), 140.
85. Carpenter, J. M.; Zhong, F.; Ragusa, M. J.; Louro, R. O.; Hogan, D. A.; Pletneva, E. V.,
Structure and redox properties of the diheme electron carrier cytochrome c4 from
Pseudomonas aeruginosa. Journal of inorganic biochemistry 2020, 203, 110889.
86. Bonfils, C.; Bec, N.; Larroque, C.; Del Rio, M.; Gongora, C.; Pugnière, M.; Martineau, P., Cyclophilin A as negative regulator of apoptosis by sequestering cytochrome c. Biochemical and biophysical research communications 2010, 393, (2), 325-330.
87. Lee, S. P.; Hwang, Y. S.; Kim, Y. J.; Kwon, K.-S.; Kim, H. J.; Kim, K.; Chae, H. Z., Cyclophilin a binds to peroxiredoxins and activates its peroxidase activity. Journal of Biological Chemistry 2001, 276, (32), 29826-29832.
88. Lovley, D. R., Electromicrobiology. Annual review of microbiology 2012, 66, 391-409.
89. Roset, M. S.; Fernández, L. G.; DelVecchio, V. G.; Briones, G., Intracellularly induced cyclophilins play an important role in stress adaptation and virulence of Brucella abortus. Infection and immunity 2013, 81, (2), 521-530.
90. Liu, X.; Wang, S.; Xu, A.; Zhang, L.; Liu, H.; Ma, L. Z., Biological synthesis of high- conductive pili in aerobic bacterium Pseudomonas aeruginosa. Applied microbiology and biotechnology 2019, 103, (3), 1535-1544.
91. Wang, W.; Du, Y.; Yang, S.; Du, X.; Li, M.; Lin, B.; Zhou, J.; Lin, L.; Song, Y.; Li, J., Bacterial Extracellular Electron Transfer Occurs in Mammalian Gut. Analytical chemistry 2019, 91, (19), 12138-12141.
92. Kim, M. Y.; Kim, C.; Ainala, S. K.; Bae, H.; Jeon, B.-H.; Park, S.; Kim, J. R., Metabolic shift of Klebsiella pneumoniae L17 by electrode-based electron transfer using glycerol in a microbial fuel cell. Bioelectrochemistry 2019, 125, 1-7.
93. Giladi, M.; Porat, Y.; Blatt, A.; Wasserman, Y.; Kirson, E. D.; Dekel, E.; Palti, Y., Microbial growth inhibition by alternating electric fields. Antimicrobial agents and chemotherapy 2008, 52, (10), 3517-3522.
94. Fertey, J.; Bayer, L.; Grunwald, T.; Pohl, A.; Beckmann, J.; Gotzmann, G.; Casado, J.
P.; Schönfelder, J.; Rögner, F.-H.; Wetzel, C., Pathogens inactivated by low-energy- electron irradiation maintain antigenic properties and induce protective immune responses. Viruses 2016, 8, (11), 319.
95. Bayer, L.; Fertey, J.; Ulbert, S.; Grunwald, T., Immunization with an adjuvanted low- energy electron irradiation inactivated respiratory syncytial virus vaccine shows immunoprotective activity in mice. Vaccine 2018, 36, (12), 1561-1569.
96. Valle, A.; Zanardini, E.; Abbruscato, P.; Argenzio, P.; Lustrato, G.; Ranalli, G.; Sorlini, C., Effects of low electric current (LEC) treatment on pure bacterial cultures. Journal of applied microbiology 2007, 103, (5), 1376-1385.
97. Angelaalincy, M. J.; Navanietha Krishnaraj, R.; Shakambari, G.; Ashokkumar, B.; Kathiresan, S.; Varalakshmi, P. J. F. i. E. R., Biofilm engineering approaches for improving the performance of microbial fuel cells and bioelectrochemical systems.
2018, 6, 63.
98. Balasubramaniam, A.; Adi, P.; Keshari, S.; Sankar, R.; Chen, C.-L.; Huang, C.-M. J. S. r., Repurposing INCI-registered compounds as skin prebiotics for probiotic Staphylococcus epidermidis against UV-B. 2020, 10, (1), 1-10.
99. Ni, S.; Yuan, Y.; Huang, J.; Mao, X.; Lv, M.; Zhu, J.; Shen, X.; Pei, J.; Lai, L.; Jiang, H., Discovering potent small molecule inhibitors of cyclophilin A using de novo drug design approach. Journal of medicinal chemistry 2009, 52, (17), 5295-5298.
100. Balasubramaniam, A.; Adi, P.; Do Thi, T. M.; Yang, J.-H.; Labibah, A. S.; Huang, C.- M. J. M., Skin Bacteria Mediate Glycerol Fermentation to Produce Electricity and Resist UV-B. 2020, 8, (7), 1092.

49
101. Halder, S.; Yadav, K. K.; Sarkar, R.; Mukherjee, S.; Saha, P.; Haldar, S.; Karmakar, S.;
Sen, T., Alteration of Zeta potential and membrane permeability in bacteria: a study with cationic agents. SpringerPlus 2015, 4, (1), 1-14.
102. Keshari, S.; Balasubramaniam, A.; Myagmardoloonjin, B.; Herr, D. R.; Negari, I. P.; Huang, C. M., Butyric Acid from Probiotic Staphylococcus epidermidis in the Skin Microbiome Down-Regulates the Ultraviolet-Induced Pro-Inflammatory IL-6 Cytokine via Short-Chain Fatty Acid Receptor. Int J Mol Sci 2019, 20, (18).
103. Marito, S.; Keshari, S.; Huang, C.-M. J. I. J. o. M. S., PEG-8 Laurate Fermentation of Staphylococcus epidermidis Reduces the Required Dose of Clindamycin Against Cutibacterium acnes. 2020, 21, (14), 5103.
104. Read, S. T.; Dutta, P.; Bond, P. L.; Keller, J.; Rabaey, K., Initial development and structure of biofilms on microbial fuel cell anodes. BMC microbiology 2010, 10, (1), 98.
105. Goodarzi, A.; Mozafarpoor, S.; Bodaghabadi, M.; Mohamadi, M., The potential of probiotics for treating acne vulgaris: A review of literature on acne and microbiota. Dermatologic Therapy 2020.
106. Modestra, J. A.; Mohan, S. V., Bio-electrocatalyzed electron efflux in Gram positive and Gram negative bacteria: an insight into disparity in electron transfer kinetics. RSC advances 2014, 4, (64), 34045-34055.
107. Di Domenico, E. G.; Petroni, G.; Mancini, D.; Geri, A.; Palma, L. D.; Ascenzioni, F.,
Development of electroactive and anaerobic ammonium-oxidizing (anammox) biofilms from digestate in microbial fuel cells. BioMed research international 2015, 2015.
108. Liu, R.; Zhao, Y.; Lu, S.; Huang, Q., Electricity generation from lactate using microbial fuel cell and the distribution characteristics of anode microbial community. Wei sheng wu xue bao= Acta microbiologica Sinica 2012, 52, (6), 744-752.
109. Marsili, E.; Baron, D. B.; Shikhare, I. D.; Coursolle, D.; Gralnick, J. A.; Bond, D. R., Shewanella secretes flavins that mediate extracellular electron transfer. Proc Natl Acad Sci U S A 2008, 105, (10), 3968-73.
110. Chen, B.; Li, F.; Liu, N.; Ge, F.; Xiao, H.; Yang, Y., Role of extracellular polymeric substances from Chlorella vulgaris in the removal of ammonium and orthophosphate under the stress of cadmium. Bioresource technology 2015, 190, 299-306.
111. Hong, B.; Joe, M.; Selvakumar, G.; Kim, K.; Choi, J.; Sa, T., Influence of salinity variations on exocellular polysaccharide production, biofilm formation and flocculation in halotolerant bacteria. Journal of Environmental Biology 2017, 38, (4), 657.
112. Christenson, L., Algal biofilm production and harvesting system for wastewater treatment with biofuels by-products. 2011.
113. Angelaalincy, M.; Senthilkumar, N.; Karpagam, R.; Kumar, G. G.; Ashokkumar, B.; Varalakshmi, P., Enhanced extracellular polysaccharide production and self-sustainable electricity generation for PAMFCs by Scenedesmus sp. SB1. ACS omega 2017, 2, (7),
3754-3765.
114. Choi, O.; Sang, B.-I., Extracellular electron transfer from cathode to microbes:
application for biofuel production. Biotechnology for Biofuels 2016, 9, (1), 11.
115. Rabaey, K.; Rozendal, R. A., Microbial electrosynthesis - revisiting the electrical route for microbial production. Nat Rev Microbiol 2010, 8, (10), 706-16.
116. Pinchuk, G. E.; Geydebrekht, O. V.; Hill, E. A.; Reed, J. L.; Konopka, A. E.; Beliaev, A. S.; Fredrickson, J. K., Pyruvate and lactate metabolism by Shewanella oneidensis MR-1 under fermentation, oxygen limitation, and fumarate respiration conditions. Appl. Environ. Microbiol. 2011, 77, (23), 8234-8240.
117. Angelaalincy, M. J.; Navanietha Krishnaraj, R.; Shakambari, G.; Ashokkumar, B.; Kathiresan, S.; Varalakshmi, P., Biofilm engineering approaches for improving the

50
performance of microbial fuel cells and bioelectrochemical systems. Frontiers in
Energy Research 2018, 6, 63.
118. Schwarz, A.; Bruhs, A.; Schwarz, T., The short-chain fatty acid sodium butyrate functions as a regulator of the skin immune system. Journal of Investigative Dermatology 2017, 137, (4), 855-864.
119. Christensen, G. J.; Scholz, C. F.; Enghild, J.; Rohde, H.; Kilian, M.; Thürmer, A.; Brzuszkiewicz, E.; Lomholt, H. B.; Brüggemann, H. J. B. g., Antagonism between Staphylococcus epidermidis and Propionibacterium acnes and its genomic basis. 2016,
17, (1), 1-14.
120. Wang, Y.; Kuo, S.; Shu, M.; Yu, J.; Huang, S.; Dai, A.; Two, A.; Gallo, R. L.; Huang, C.-M. J. A. m.; biotechnology, Staphylococcus epidermidis in the human skin microbiome mediates fermentation to inhibit the growth of Propionibacterium acnes: implications of probiotics in acne vulgaris. 2014, 98, (1), 411-424.
121. Claudel, J.-P.; Auffret, N.; Leccia, M.-T.; Poli, F.; Corvec, S.; Dréno, B. J. D., Staphylococcus epidermidis: a potential new player in the physiopathology of acne?
2019, 235, (4), 287-294.
122. Kim, J. J. D., Review of the innate immune response in acne vulgaris: activation of Toll- like receptor 2 in acne triggers inflammatory cytokine responses. 2005, 211, (3), 193-
198.
123. Hoare, J. I.; Rajnicek, A. M.; McCaig, C. D.; Barker, R. N.; Wilson, H. M. J. J. o. l. b., Electric fields are novel determinants of human macrophage functions. 2016, 99, (6),
1141-1151.
124. Nakatsuji, T.; Chiang, H.-I.; Jiang, S. B.; Nagarajan, H.; Zengler, K.; Gallo, R. L. J. N. c., The microbiome extends to subepidermal compartments of normal skin. 2013, 4, (1),
1-8.
125. Pouillot, A.; Polla, A.; S Polla, B., Iron and iron chelators: a review on potential effects on skin aging. Current aging science 2013, 6, (3), 225-231.
126. Giladi, M.; Porat, Y.; Blatt, A.; Wasserman, Y.; Kirson, E. D.; Dekel, E.; Palti, Y., Microbial Growth Inhibition by Alternating Electric Fields. Antimicrobial Agents and Chemotherapy 2008, 52, (10), 3517.
127. Pakhomova, O. N.; Gregory, B. W.; Semenov, I.; Pakhomov, A. G., Two modes of cell death caused by exposure to nanosecond pulsed electric field. PLoS One 2013, 8, (7), e70278.
128. Kirson, E. D.; Gurvich, Z.; Schneiderman, R.; Dekel, E.; Itzhaki, A.; Wasserman, Y.; Schatzberger, R.; Palti, Y., Disruption of cancer cell replication by alternating electric fields. Cancer Res 2004, 64, (9), 3288-95.
129. Pillet, F.; Formosa-Dague, C.; Baaziz, H.; Dague, E.; Rols, M.-P., Cell wall as a target for bacteria inactivation by pulsed electric fields. Scientific Reports 2016, 6, (1), 19778.
130. Yeh, J. I.; Chinte, U.; Du, S., Structure of glycerol-3-phosphate dehydrogenase, an essential monotopic membrane enzyme involved in respiration and metabolism. Proc Natl Acad Sci U S A 2008, 105, (9), 3280-5.
131. Massey, T. H.; Mercogliano, C. P.; Yates, J.; Sherratt, D. J.; Lowe, J., Double-stranded
DNA translocation: structure and mechanism of hexameric FtsK. Mol Cell 2006, 23, (4),
457-69.
132. Carballido-Lopez, R.; Errington, J., A dynamic bacterial cytoskeleton. Trends Cell Biol
2003, 13, (11), 577-83.
133. Felder, C. E.; Prilusky, J.; Silman, I.; Sussman, J. L., A server and database for dipole moments of proteins. Nucleic Acids Res 2007, 35, (Web Server issue), W512-21.

51
134. Ahimou, F.; Paquot, M.; Jacques, P.; Thonart, P.; Rouxhet, P. G., Influence of electrical
properties on the evaluation of the surface hydrophobicity of Bacillus subtilis. J Microbiol Methods 2001, 45, (2), 119-26.

指導教授

黃俊銘(Chun-Ming Huang)

審核日期

2021-7-27

推文