本研究探討顆粒物質(Particultate Matter, PM)對於金黃色葡萄球菌(S. aureus)與產吲哚金黃桿菌(C. indologenes)生物膜形成之影響，實驗以染色吸光值法定量生物膜累積量，並利用電子顯微鏡拍攝生物膜的表面型態。另外，本研究也利用染色吸光值測量在生物膜累積過程中浮游態的細菌活力。顆粒物質皆購自美國國家標準暨技術研究院(National Institute of Standards and Technology, NIST)，分別為SRM 1633c (Trace Elements in Coal Fly Ash)、SRM 1648a (Urban Particulate Matter)、SRM 2709a (San Joaquin Soil)及SRM 2711a (Montana II Soil)。
本研究發現顆粒物質皆會大幅增加細菌的生物膜累積量。S. aureus在添加顆粒物質後生物膜多寡關係相對於控制組為SRM 2711a (2.41倍) > SRM 1648a (1.81倍) > SRM 1633c (1.16倍)，而C. indologenes生物膜累積量相對於控制組為SRM 2709a (12.64倍) > SRM 2711a (7.05倍) > SRM 1633c (3.60倍)。電子顯微鏡(SEM)的影像也證實SRM2711a可使S. aureus形成最緊密的生物膜結構，並且觀察到S. aureus形成的生物膜會更集中於顆粒物質周圍及粗糙不規則的顆粒表面。在兩種實驗菌株的實驗中皆可以觀察到顆粒物質會促進生物膜累積，並且推測顆粒物質上的化學成分差異及鉻元素含量的多寡導致促進生物膜累積能力的差異。另外， C. indologenes因為菌落間差異較大導致生物膜累積量有較大的標準差。
本研究也觀察到S. aureus在添加SRM 2711a與SRM 1648a後，浮游態細菌的代謝能力相對於控制組分別降低14.5 % (SRM 2711a)及11.8 % (SRM 1648a)，而加入SRM 1633c後與控制組的差異(1.7 %)並不明顯。另外C. indologenes在添加顆粒物質後，代謝能力相對於控制組分別減少46.0 % (SRM 1633c)、45.6 % (SRM 2711a)及36.4 % (SRM 2709a)，可知在生物膜累積的過程中顆粒物質會分別降低與提升浮游態中S. aureus及C. indologenes的代謝能力。
本研究證實顆粒物質會促進金黃色葡萄球菌及產吲哚金黃桿菌生物膜的生成，但對於兩種菌株浮游態細菌代謝能力的影響相反。未來建議使用其他成分或是尺寸不同的顆粒物質進行實驗，觀察其中特有的物質(如：微量元素、鉻元素及多環芳香烴等有機物質)如何影響細菌生物膜的累積情況，並使用多變量分析建立資料庫，以冀提供更精確的顆粒物質致病機制，進而降低人體因吸入顆粒物質所造成的健康風險。

This study investigated the effects of particulate matter on the biofilm formation of Staphylococcus aureus(S. aureus) and Chryseobacterium indologenes (C. indologenes). Biofilm amount was quantified using crystal violet labeling and the surface morphology of biofilm was obtained by the scanning electron microscope. In addition, the metabolic viability of the bacteria in the planktonic state during the accumulation of the biofilm was measured using alamarBlue™ labeling. All particulate matters were purchased from the National Institute of Standards and Technology (NIST), including SRM 1633c (Trace Elements in Coal Fly Ash), SRM 1648a (Urban Particulate Matter), SRM 2709a (San Joaquin Soil), and SRM 2711a (Montana II Soil).
Results showed that particulate matters greatly increased the accumulation of bacterial biofilm. Compared with the control, the amount of S. aureus biofilm after the addition of particulate matters increased to 2.41 folds for SRM 2711a, 1.81 folds for SRM 1648a, and 1.16 folds for SRM 1633c; while the C. indologenes biofilm accumulation to 12.64 folds for SRM 2709a, 7.05 folds for SRM 2711a, and 3.60 folds for SRM 1633c. Scanning electron microscope(SEM) images discovered that SRM 2711a induced S. aureus to form the most condense biofilm structure, and the biofilm formed by S. aureus was more concentrated around the particulate matter, especially for those with rough and irregular surfaces. The results of both bacteria strains showed that the particulate matters promoted the accumulation of biofilm, probably attributed by the various chemical compositions of the particulate matter and the high concentrations of chromium. Additionally, the results of C. indologenes were more diverse than S. aureus because of the heterogeneous responses towards the particulate matters among different colonies.
This study also observed that after adding SRM 2711a and SRM 1648a, the metabolic activity of S. aureus decreased by 14.5 % (SRM 2711a) and 11.8 % (SRM 1648a) compared to the control group, however, the effect of adding SRM 1633c (+1.7 %) wasn’t obvious. On the other hand, the metabolic activity of C. indologenes increased by 46.0 % (SRM 1633c), 45.6 % (SRM 2711a) and 36.4 % (SRM 2709a) compared to the control group after adding particulate matter. These data indicate that during the biofilm accumulation process, particulate matters have opposite effects toward the metabolic ability of S. aureus and C. indologenes in the planktonic state.
In conclusion, this study showed that particulate matters can promote the formation of biofilms of S. aureus and C.indologenes, but their effects on the metabolic activity of planktonic cells of these two strains were opposite. In the future, more particulate matters of different sizes or compositions should be used to observe how specific substances (eg. trace elements, polycyclic aromatic hydrocarbons, and other organic substances) affect the accumulation of bacterial biofilms. Combining the experimental data with multivariate analysis, a database can be established to provide a more precise pathogenic mechanism of particulate matters, thereby reducing their risk to human health.

摘要 i
Abstract iii
致謝 v
目錄 vi
表目錄 viii
圖目錄 ix
第一章 緒論 1
1.1 介紹 1
1.2 實驗目的與規劃 2
第二章 文獻回顧 3
2.1 顆粒物質(Particulate Matter, PM) 3
2.1.1 顆粒物質(Particulate Matter, PM)的來源及分類 4
2.1.2 顆粒物質(Particulate Matter, PM)與人類疾病關聯 7
2.1.3 顆粒物質(Particulate Matter, PM)對於微生物的影響 10
2.2 微生物族群(Microbiota) 13
2.2.1 微生物對人體的影響 13
2.2.2 人體疾病與微生物關聯 15
2.3 生物膜(Biofilm) 21
2.3.1 生物膜的形成 22
2.3.2 致病菌之生物膜與人類疾病關聯 24
第三章 實驗方法與材料 29
3.1 微生物培養方法 30
3.1.1 微生物固態培養(細菌維持) 30
3.1.2 微生物培養液配製 31
3.2 實驗用顆粒物質 33
3.2.1 SRM 1633c – Trace Elements in Coal Fly Ash 33
3.2.2 SRM 1648a – Urban Particulate Matter 35
3.2.3 SRM 2709a – San Joaquin Soil 37
3.2.4 SRM 2711a – Montana II Soil 39
3.2.5 顆粒物質濃度 41
3.3 顆粒物質與細菌培養 42
3.3.1 控制細菌液態培養初始濃度 42
3.3.2 液態培養 44
3.3.3 生物膜定量及觀測方法 45
3.3.4 浮游態細菌染色吸光值定量方法 48
第四章 結果與討論 49
4.1 金黃色葡萄球菌S. aureus生物膜 49
4.1.1 顆粒物質對S. aureus生物膜累積之影響 49
4.1.2 顆粒物質對S. aureus生物膜表面形態之影響(SEM) 51
4.2 金黃色葡萄球菌S. aureus浮游態代謝能力的影響 57
4.3 顆粒物質對產吲哚金黃桿菌C. indologenes的影響 59
4.3.1 C. indologenes生物膜累積之影響 60
4.3.2 C. indologenes浮游態細菌代謝能力之影響 63
4.4 顆粒尺寸對細菌生長的影響 65
第五章 結論與未來展望 69
5.1 結論 69
5.2 未來展望 71
參考文獻 72
附錄 80

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