高鹽環境如鹽田，其獨特的生態位使生存在此環境中的多種微生物生產具生物活性二次代謝物的潛力。本實驗中吾人同時使用分離培養和總體基因體方法分析臺灣台南北門、七股及井仔腳三個鹽田的土壤樣本的細菌群落多樣性及抗微生物活性。使用三種培養基，吾人總共分離出343株細菌。經過16s rDNA序列比對後將這些細菌分成4個門：厚壁菌門(Firmicutes, 56.0%)、變形菌門(Proteobacteria, 40.0%)、放線菌門(Actinomycetota, 3.5%)及擬桿菌門(Bacteroidetes, 0.5%)。其中有51株(14.9%)在使用洋菜錠(agar block)抗菌試驗時，至少對一種測試菌株表現出抗菌活性。親緣關係分析顯示，這些分離株屬於以下10個細菌屬：Bacillus (28), Vibrio (15), Halomonas (3), Streptomyces (2), Nocardiopsis (1), Virgibacillus (1), Pseudoalteromonas (1), Marinobacter (1), Micrococcus (1), and Idiomarina (1)。其中菌株編號G-B-SCA10-1-1、G-A-SCA10-16、B-B-SCA3-8和B-B-SCA3-9四個分離株，同時具有抗菌和抗癌活性，是進一步天然產物分離和特性研究的良好候選者。
為了了解鹽田土壤中細菌菌群的多樣性，吾人使用次世代16S rDNA擴增子分析土壤樣品。共獲得了793,149條序列，以97%相似度進行分群後，獲得了415個OTUs。採集的鹽田土壤中的細菌群落總共可分為43個門，其中含量較多的有：尚未被分類(unclassified; 47.0%)、擬桿菌門(Bacteroidetes; 19.6%)、Patescibacteria門(10.4%)和軟壁菌門(Tenericutes; 6.3%)。吾人研究結果顯示了，高鹽環境中的細菌在藥物開發上具有極大的潛力。

Hypersaline environments, such as solar salterns, provide a unique ecological niche for diverse microorganisms with the potential to produce bioactive secondary metabolites. A combination of culture-based and metagenomic approaches was used to characterize diversity and antimicrobial activities of bacteria from soil samples collected from three salterns, Beimen, Chiku, and Gingzaijiao, at Tainan, Taiwan. A total of 343 bacteria were isolated from soil samples using three different media. These bacterial isolates belong to four phyla, namely Firmicutes (56.0%), Proteobacteria (40.0%), Actinomycetota (3.5%), and Bacteroidetes (0.5%) based on the 16S rRNA gene sequence. Among them, 51 isolates (14.9%) were found to exhibit antimicrobial activity against at least one indicator microbe using agar block method. Phylogenetic analysis indicated these isolates belong to the following ten bacterial genera: Bacillus (28), Vibrio (15), Halomonas (3), Streptomyces (2), Nocardiopsis (1), Virgibacillus (1), Pseudoalteromonas (1), Marinobacter (1), Micrococcus (1), and Idiomarina (1). Four isolates, namely G-B-SCA10-1-1, G-A-SCA10-16, B-B-SCA3-8 and, B-B-SCA3-9 which have high antimicrobial and cytotoxic activities were good candidates for further natural product isolation and characterization research.
To understand the diversity of bacterial communities in soil collected from the salterns, we also investigate the soil samples by using next-generation 16S rRNA amplicon sequencing. A total of 793,149 sequences were obtained and clustered to 415 operational taxonomic units (OUTs; 97% sequence similarity). The bacterial communities in soil collected from the salt fields were assigned to 43 bacterial phyla and revealed abundant of phyla unclassified (47.0%), Bacteroidetes (19.6%), Patescibacteria (10.4%), and Tenericutes (6.3%). Our results demonstrate that bacteria from hypersaline environments could be a source of bacteria strains which have a great potential in discovery of useful medical molecules.

中文摘要 I
Abstract III
目錄 V
圖目錄 VII
表目錄 IX
第一章、緒論 1
第一節、前言 1
第二節、微生物天然物(microbial natural products) 1
第三節、高鹽環境與嗜鹽菌和耐鹽菌 2
第四節、嗜鹽菌的應用及其抗菌和抗癌活性 3
第五節、高鹽環境微生物多樣性 5
第六節、傳統培養方法及總體基因體學(metagenomics) 6
第七節、實驗動機與目的 7
第二章、實驗材料與方法 11
第一節、藥品、儀器與培養基 11
一、藥品 11
二、實驗儀器 13
三、選擇性培養基 14
四、菌種培養基 16
五、實驗用菌株及細胞株 17
第二節、樣本來源與採集 17
第三節、可培養嗜鹽及耐鹽細菌的分離與培養 18
一、樣本前處理 18
二、平板培養及活菌計數 18
三、細菌篩選與純化 18
四、菌種冷凍保存 19
第四節、16S rDNA序列鑑定及親緣關係分析(phylogenetic analysis) 19
一、萃取與純化細菌基因體DNA 19
二、利用聚合酶連鎖反應(polymerase chain reation, PCR)擴增16S
rDNA片段 20
三、DNA電泳分析 20
四、定序 21
五、序列比對與參考菌株 21
六、分子親緣關係分析 21
第五節、菌株抗菌活性及鹽度適應測試 22
一、抗菌活性目標菌株培養 22
二、洋菜錠(agar block)抗菌活性試驗 22
三、抗菌活性初次篩選(primary screening) 23
四、抗菌活性二次篩選 23
五、鹽度適應測試 23
第六節、菌株粗萃物之細胞毒殺活性分析 24
一、菌液培養及萃取濃縮 24
二、癌細胞培養及細胞毒性(cell toxicity)試驗(MTT assay) 24
第七節、鹽田土壤細菌多樣性總體基因體學(metagenomic)分析 25
一、萃取與純化鹽田土壤細菌體DNA 25
二、次世代定序(next generation sequencing) 26
三、metagenomic序列生物資訊學分析 26
四、OTU (operational taxonomic units)分析 28
五、稀釋性曲線分析(rarefaction curve analysis) 28
六、多樣性分析(diversity analysis) 28
第三章、結果 31
第一節、鹽田土壤分離細菌的多樣性與抗菌活性 31
一、鹽田土壤樣本於選擇性培養基生長菌數 31
二、鹽田土壤可培養細菌16S rDNA序列分析 34
三、鹽田土壤可培養細菌16s rDNA序列之分子親緣樹分析 40
四、可培養菌株初步抗菌活性篩選 40
五、抗菌活性二次篩選 40
六、具抗菌活性菌株16S rDNA序列分析 50
七、鹽田土壤具抗菌活性菌株鹽度適應測試 50
八、鹽田土壤分離菌株培養液粗萃 54
九、鹽田土壤菌株粗萃物之細胞毒性 54
第二節、鹽田土壤細菌的metagenomic分析 58
一、鹽田土壤次世代定序分析 58
二、alpha多樣性分析 58
三、beta多樣性分析 64
四、分類學分析 64
五、可培養細菌及總體基因體學多樣性比較 64
第四章、討論 71
第一節、鹽田分離細菌的抗菌活性 71
第二節、鹽田細菌多樣性 73
第三節、結論 74
參考文獻 77

Abd-Elnaby, H., Abo-Elala, G., Abdel-Raouf, U., Abd-elwahab, A., Hamed, M., 2016. Antibacterial and anticancer activity of marine Streptomyces parvus: optimization and application. Biotechnology & Biotechnological Equipment 30, 180-191.
Abesinghe, A., Islam, N., Vidanarachchi, J., Prakash, S., Silva, K., Karim, M., 2019. Effects of ultrasound on the fermentation profile of fermented milk products incorporated with lactic acid bacteria. International Dairy Journal 90, 1-14.
Ahmed, T., Shahid, M., Noman, M., Niazi, M.B.K., Zubair, M., Almatroudi, A., Khurshid, M., Tariq, F., Mumtaz, R., Li, B., 2020. Bioprospecting a native silver-resistant Bacillus safensis strain for green synthesis and subsequent antibacterial and anticancer activities of silver nanoparticles. Journal of Advanced Research 24, 475-483.
Almasi, F., Mohammadipanah, F., Adhami, H.R., Hamedi, J., 2018. Introduction of marine‐derived Streptomyces sp. UTMC 1334 as a source of pyrrole derivatives with anti‐acetylcholinesterase activity. Journal of Applied Microbiology 125, 1370-1382.
Alrumman, S., Mostafa, Y., Al-Izran, K.A., Alfaifi, M., Taha, T., Elbehairi, S., 2019. Production and anticancer activity of an L-asparaginase from Bacillus licheniformis isolated from the Red Sea, Saudi Arabia. Scientific Reports 9, 1-14.
Altschul, S.F., Gish, W., Miller, W., Myers, E.W., Lipman, D.J., 1990. Basic local alignment search tool. Journal of Molecular Biology 215, 403-410.
Amberkar, U., Khandeparker, R., Parab, P., 2019. Nitrate reductase gene expression in Idiomarina strain cos21 obtained from oxygen minimum zone of Arabian sea. Current Microbiology 76, 63-69.
Andreo-Vidal, A., Sanchez-Amat, A., Campillo-Brocal, J.C., 2018. The Pseudoalteromonas luteoviolacea L-amino acid oxidase with antimicrobial activity is a flavoenzyme. Marine Drugs 16, 499.
Anh, H.T.H., Shahsavari, E., Bott, N.J., Ball, A.S., 2021. Application of co-culture technology to enhance protease production by two halophilic bacteria, Marinirhabdus sp. and Marinobacter hydrocarbonoclasticus. Molecules 26, 3141.
Arunachalam, K., Appadorai, R.A.J., 2013. Antioxidant potential and biochemical evaluation of metabolites from the marine bacteria Virgibacillus sp. associated with the sponge Callyspongia diffusa. Free Radicals and Antioxidants 3, 47-51.
Asker, M.M.S., Sayed, O.H.E., Mahmoud, M.G., Ramadan, M.F., 2014. Chemical structure and antioxidant activity of a new exopolysaccharide produced from Micrococcus luteus. Journal of Genetic Engineering and Biotechnology 12, 121-126.
Athukoralage, P.S., Herath, H.M.T.B., Deraniyagala, S.A., Wijesundera, R.L.C., Weerasinghe, P.A., 2001. Antifungal constituent from Gordonia dassanayakei. Fitoterapia 72, 565-567.
Baker, G., Smith, J.J., Cowan, D.A., 2003. Review and re-analysis of domain-specific 16S primers. Journal of Microbiological Methods 55, 541-555.
Behjati, S., Tarpey, P.S., 2013. What is next generation sequencing? Archives of Disease in Childhood-Education and Practice 98, 236-238.
Béjar, V., Llamas, I., Calvo, C., Quesada, E., 1998. Characterization of exopolysaccharides produced by 19 halophilic strains of the species Halomonas eurihalina. Journal of Biotechnology 61, 135-141.
Bennur, T., Kumar, A.R., Zinjarde, S., Javdekar, V., 2015. Nocardiopsis species: Incidence, ecological roles and adaptations. Microbiological Research 174, 33-47.
Bibi, F., Yasir, M., Al-Sofyani, A., Naseer, M.I., Azhar, E.I., 2020. Antimicrobial activity of bacteria from marine sponge Suberea mollis and bioactive metabolites of Vibrio sp. EA348. Saudi Journal of Biological Sciences 27, 1139-1147.
Bitzer, J., Große, T., Wang, L., Lang, S., Beil, W., Zeeck, A., 2006. New aminophenoxazinones from a marine Halomonas sp.: fermentation, structure elucidation, and biological activity. The Journal of Antibiotics 59, 86-92.
Blaxter, M., Mann, J., Chapman, T., Thomas, F., Whitton, C., Floyd, R., Abebe, E., 2005. Defining operational taxonomic units using DNA barcode data. Philosophical Transactions of the Royal Society B: Biological Sciences 360, 1935-1943.
Bowman, J.P., 2007. Bioactive compound synthetic capacity and ecological significance of marine bacterial genus Pseudoalteromonas. Marine Drugs 5, 220-241.
Brito, E.M.S., Guyoneaud, R., Goñi-Urriza, M., Ranchou-Peyruse, A., Verbaere, A., Crapez, M.A., Wasserman, J.C.A., Duran, R., 2006. Characterization of hydrocarbonoclastic bacterial communities from mangrove sediments in Guanabara Bay, Brazil. Research in Microbiology 157, 752-762.
Brooks, J.P., Edwards, D.J., Harwich, M.D., Rivera, M.C., Fettweis, J.M., Serrano, M.G., Reris, R.A., Sheth, N.U., Huang, B., Girerd, P., 2015. The truth about metagenomics: quantifying and counteracting bias in 16S rRNA studies. BMC Microbiology 15, 1-14.
Bultel-Poncé, V., Debitus, C., Berge, J.P., Cerceau, C., Guyot, M., 1998. Metabolites from the sponge-associated bacterium Micrococcus luteus. Journal of Marine Biotechnology 6, 233-236.
Calvo, C., Martínez-Checa, F., Toledo, F., Porcel, J., Quesada, E., 2002. Characteristics of bioemulsifiers synthesised in crude oil media by Halomonas eurihalina and their effectiveness in the isolation of bacteria able to grow in the presence of hydrocarbons. Applied Microbiology and Biotechnology 60, 347-351.
Chakraborty, S., Jana, S., Gandhi, A., Sen, K.K., Zhiang, W., Kokare, C., 2014. Gellan gum microspheres containing a novel α-amylase from marine Nocardiopsis sp. strain B2 for immobilization. International Journal of Biological Macromolecules 70, 292-299.
Chao, A., 1984. Nonparametric estimation of the number of classes in a population. Scandinavian Journal of Statistics, 265-270.
Chao, A., Lee, S.-M., 1992. Estimating the number of classes via sample coverage. Journal of the American Statistical Association 87, 210-217.
Chen, Y.-H., Kuo, J., Sung, P.-J., Chang, Y.-C., Lu, M.-C., Wong, T.-Y., Liu, J.-K., Weng, C.-F., Twan, W.-H., Kuo, F.-W., 2012. Isolation of marine bacteria with antimicrobial activities from cultured and field-collected soft corals. World Journal of Microbiology and Biotechnology 28, 3269-3279.
Chen, Z., Ou, P., Liu, L., Jin, X., 2020. Anti-MRSA activity of actinomycin X2 and collismycin a produced by Streptomyces globisporus WA5-2-37 from the intestinal tract of American cockroach (Periplaneta americana). Frontiers in Microbiology 11, 555.
Chitte, R., Dey, S., 2000. Potent fibrinolytic enzyme from a thermophilic Streptomyces megasporus strain SD5. Letters in Applied Microbiology 31, 405-410.
Cole, J.R., Chai, B., Farris, R.J., Wang, Q., Kulam, S., McGarrell, D.M., Garrity, G.M., Tiedje, J.M., 2005. The Ribosomal Database Project (RDP-II): sequences and tools for high-throughput rRNA analysis. Nucleic Acids Research 33, D294-D296.
Conde-Martínez, N., Acosta-González, A., Díaz, L.E., Tello, E., 2017. Use of a mixed culture strategy to isolate halophilic bacteria with antibacterial and cytotoxic activity from the Manaure solar saltern in Colombia. BMC Microbiology 17, 1-12.
Coppola, R., Iorizzo, M., Saotta, R., Sorrentino, E., Grazia, L., 1997. Characterization of Micrococci and Staphylococci isolated from soppressata molisana, a Southern Italy fermented sausage. Food Microbiology 14, 47-53.
Coronado, M.-J., Vargas, C., Hofemeister, J., Ventosa, A., Nieto, J.J., 2000. Production and biochemical characterization of an α-amylase from the moderate halophile Halomonas meridiana. FEMS Microbiology Letters 183, 67-71.
Dastager, S.G., Deepa, C., Pandey, A., 2010. Isolation and characterization of novel plant growth promoting Micrococcus sp NII-0909 and its interaction with cowpea. Plant Physiology and Biochemistry 48, 987-992.
DeLong, E.F., Pace, N.R., 2001. Environmental diversity of bacteria and archaea. Systematic Biology 50, 470-478.
Dheilly, A., Soum-Soutéra, E., Klein, G.L., Bazire, A., Compère, C., Haras, D., Dufour, A., 2010. Antibiofilm activity of the marine bacterium Pseudo- alteromonas sp. strain 3J6. Applied and Environmental Microbiology 76, 3452-3461.
Doghri, I., Portier, E., Desriac, F., Zhao, J.M., Bazire, A., Dufour, A., Rochette, V., Sablé, S., Lanneluc, I., 2020. Anti-biofilm activity of a low weight proteinaceous molecule from the marine bacterium Pseudoalteromonas sp. IIIA004 against marine bacteria and human pathogen biofilms. Microorganisms 8, 1295.
Dou, L., Zhang, M., Pan, L., Liu, L., Su, Z., 2022. Sulfide removal characteristics, pathways and potential application of a novel chemolithotrophic sulfide-oxidizing strain, Marinobacter sp. SDSWS8. Environmental Research 212, 113176.
Du, Y., Ma, J., Yin, Z., Liu, K., Yao, G., Xu, W., Fan, L., Du, B., Ding, Y., Wang, C., 2019. Comparative genomic analysis of Bacillus paralicheniformis MDJK30 with its closely related species reveals an evolutionary relationship between B. paralicheniformis and B. licheniformis. BMC Genomics 20, 1-16.
Dulmage, H.T., 1970. Insecticidal activity of HD-1, a new isolate of Bacillus thuringiensis var. alesti. Journal of Invertebrate Pathology 15, 232-239.
Edgar, R.C., 2016. UNOISE2: improved error-correction for Illumina 16S and ITS amplicon sequencing. BioRxiv, 081257.
Elfalah, H., Usup, G., Ahmad, A., 2013. Anti-microbial properties of secondary metabolites of marine Gordonia tearrae extract. Journal of Agriculture Science 5, 94-101.
Eliseikina, M.G., Beleneva, I.A., Kukhlevsky, A.D., Shamshurina, E.V., 2021. Identification and analysis of the biological activity of the new strain of Pseudoalteromonas piscicida isolated from the hemal fluid of the bivalve Modiolus kurilensis (F.R. Bernard, 1983). Archives of Microbiology 203, 4461-4473.
Ericsson, B.H., Tunevall, G., Wickman, K., 1960. The paper disc method for determination of bacterial sensitivity to antibiotics: Relationship between the diameter of the zone of inhibition and the minimum inhibitory concentration. Scandinavian Journal of Clinical and Laboratory Investigation 12, 414-422.
Essghaier, B., Fardeau, M.-L., Cayol, J.-L., Hajlaoui, M., Boudabous, A., Jijakli, H., Sadfi‐Zouaoui, N., 2009. Biological control of grey mould in strawberry fruits by halophilic bacteria. Journal of Applied Microbiology 106, 833-846.
Fatholahpoor Kami, K., Ghane, M., Babaeekhou, L., 2020. Hydrolase-producing moderately halophilic bacteria from Eshtehard Desert (Iran). Microbiology 89, 769-777.
Fernandez, A.B., Ghai, R., Martin-Cuadrado, A.-B., Sanchez-Porro, C., Rodriguez-Valera, F., Ventosa, A., 2014. Prokaryotic taxonomic and metabolic diversity of an intermediate salinity hypersaline habitat assessed by metagenomics. FEMS Microbiology Ecology 88, 623-635.
Galaviz-Silva, L., Iracheta-Villarreal, J.M., Molina-Garza, Z.J., 2018. Bacillus and Virgibacillus strains isolated from three Mexican coasts antagonize Staphylococcus aureus and Vibrio parahaemolyticus. FEMS Microbiology Letters 365, fny202.
Gao, X., Lu, Y., Xing, Y., Ma, Y., Lu, J., Bao, W., Wang, Y., Xi, T., 2012. A novel anticancer and antifungus phenazine derivative from a marine actinomycete BM-17. Microbiological Research 167, 616-622.
Gomaa, M., Yousef, N., 2020. Optimization of production and intrinsic viscosity of an exopolysaccharide from a high yielding Virgibacillus salarius BM02: study of its potential antioxidant, emulsifying properties and application in the mixotrophic cultivation of Spirulina platensis. International Journal of Biological Macromolecules 149, 552-561.
Gomariz, M., Martínez-García, M., Santos, F., Rodriguez, F., Capella-Gutiérrez, S., Gabaldon, T., Rossello-Mora, R., Meseguer, I., Anton, J., 2015. From community approaches to single-cell genomics: the discovery of ubiquitous hyperhalophilic Bacteroidetes generalists. The ISME Journal 9, 16-31.
Gong, A.-D., Li, H.-P., Shen, L., Zhang, J.-B., Wu, A.-B., He, W.-J., Yuan, Q.-S., He, J.-D., Liao, Y.-C., 2015. The Shewanella algae strain YM8 produces volatiles with strong inhibition activity against Aspergillus pathogens and aflatoxins. Frontiers in Microbiology 6, 1091.
Gong, A.-D., Li, H.-P., Yuan, Q.-S., Song, X.-S., Yao, W., He, W.-J., Zhang, J.-B., Liao, Y.-C., 2015. Antagonistic mechanism of iturin A and plipastatin A from Bacillus amyloliquefaciens S76-3 from wheat spikes against Fusarium graminearum. PLOS ONE 10, e0116871.
Gupta, V., Singh, S.S., Sidhu, C., Grover, V., Pinnaka, A.K., Korpole, S., 2019. Virgicin, a novel lanthipeptide from Virgibacillus sp. strain AK90 exhibits inhibitory activity against Gram-positive bacteria. World Journal of Microbiology and Biotechnology 35, 1-14.
Hamza, A., Fdhila, K., Zouiten, D., Masmoudi, A.S., 2016. Virgibacillus proomii and Bacillus mojavensis as probiotics in sea bass (Dicentrarchus labrax) larvae: effects on growth performance and digestive enzyme activities. Fish Physiology and Biochemistry 42, 495-507.
Handelsman, J., Rondon, M.R., Brady, S.F., Clardy, J., Goodman, R.M., 1998. Molecular biological access to the chemistry of unknown soil microbes: a new frontier for natural products. Chemistry & Biology 5, R245-R249.
Head, I., Saunders, J., Pickup, R.W., 1998. Microbial evolution, diversity, and ecology: a decade of ribosomal RNA analysis of uncultivated microorganisms. Microbial Ecology 35, 1-21.
Hemamalini, R., Khare, S.K., 2018. Halophilic lipase does forms catalytically active aggregates: evidence from Marinobacter sp. EMB5 lipase (LipEMB5). International Journal of Biological Macromolecules 119, 172-179.
Huang, D., Yu, C., Shao, Z., Cai, M., Li, G., Zheng, L., Yu, Z., Zhang, J., 2020. Identification and characterization of nematicidal volatile organic compounds from deep-sea Virgibacillus dokdonensis MCCC 1A00493. Molecules 25, 744.
Hugenholtz, P., Goebel, B.M., Pace, N.R., 1998. Impact of culture-independent studies on the emerging phylogenetic view of bacterial diversity. Journal of Bacteriology 180, 4765-4774.
Ivanova, E.P., Romanenko, L.A., Chun, J., Matte, M.H., Matte, G.R., Mikhailov, V.V., Svetashev, V.I., Huq, A., Maugel, T., Colwell, R.R., 2000. Idiomarina gen. nov., comprising novel indigenous deep-sea bacteria from the Pacific Ocean, including descriptions of two species, Idiomarina abyssalis sp. nov. and Idiomarina zobellii sp. nov. International Journal of Systematic and Evolutionary Microbiology 50, 901-907.
John, J., Siva, V., Kumari, R., Arya, A., Kumar, A., 2020. Unveiling cultivable and uncultivable halophilic bacteria inhabiting Marakkanam saltpan, India and their potential for biotechnological applications. Geomicrobiology Journal 37, 691-701.
Jones, D.L., Baxter, B.K., 2017. DNA repair and photoprotection: Mechanisms of overcoming environmental ultraviolet radiation exposure in halophilic archaea. Frontiers in Microbiology 8, 1882.
Kambourova, M., Tomova, I., Boyadzhieva, I., Radchenkova, N., Vasileva-Tonkova, E., 2017. Phylogenetic analysis of the bacterial community in a crystallizer pond, Pomorie salterns, Bulgaria. Biotechnology & Biotechnological Equipment 31, 325-332.
Karpiński, T.M., Adamczak, A., 2018. Anticancer activity of bacterial proteins and peptides. Pharmaceutics 10, 54.
Kayanadath, S., Nathan, V.K., Ammini, P., 2019. Anti-biofilm activity of biosurfactant derived from Halomonas sp., a lipolytic marine bacterium from the Bay of Bengal. Microbiology 88, 585-599.
Kimura, M., 1980. A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. Journal of Molecular Evolution 16, 111-120.
Kolp, S., Pietsch, M., Galinski, E.A., Gütschow, M., 2006. Compatible solutes as protectants for zymogens against proteolysis. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics 1764, 1234-1242.
Konstantinidis, K.T., Viver, T., Conrad, R.E., Venter, S.N., Rossello-Mora, R., 2022. Solar salterns as model systems to study the units of bacterial diversity that matter for ecosystem functioning. Current Opinion in Biotechnology 73, 151-157.
Kushner, D.J., 1988. Physiology of halophilic eubacteria. Halophilic bacteria, 109-138.
Kushner, D.J., 1988. What is the" true" internal environment of halophilic and other bacteria? Canadian journal of Microbiology 34, 482-486.
Kushner, D.J., 2020. Growth and nutrition of halophilic bacteria. The Biology of Halophilic Bacteria. CRC Press, pp. 87-103.
Lagier, J.-C., Armougom, F., Million, M., Hugon, P., Pagnier, I., Robert, C., Bittar, F., Fournous, G., Gimenez, G., Maraninchi, M., 2012. Microbial culturomics: paradigm shift in the human gut microbiome study. Clinical Microbiology and Infection 18, 1185-1193.
Lagier, J.-C., Million, M., Hugon, P., Armougom, F., Raoult, D., 2012. Human gut microbiota: repertoire and variations. Frontiers in Cellular and Infection Microbiology 2, 136.
Lebbadi, M., Galvez, A., Maqueda, M., Martínez‐Bueno, M., Valdivia, E., 1994. Fungicin M4: a narrow spectrum peptide antibiotic from Bacillus licheniformis M‐4. Journal of Applied Bacteriology 77, 49-53.
Lee, S.-O., Kato, J., Takiguchi, N., Kuroda, A., Ikeda, T., Mitsutani, A., Ohtake, H., 2000. Involvement of an extracellular protease in algicidal activity of the marine bacterium Pseudoalteromonas sp. strain A28. Applied and Environmental Microbiology 66, 4334-4339.
Levandowsky, M., Winter, D., 1971. Distance between sets. Nature 234, 34-35.
Li, X., Yu, Y.H., 2015. Biodiversity and screening of halophilic bacteria with hydrolytic and antimicrobial activities from Yuncheng Salt Lake, China. Biologia 70, 151-156.
Lippert, K., Galinski, E.A., 1992. Enzyme stabilization be ectoine-type compatible solutes: protection against heating, freezing and drying. Applied Microbiology and Biotechnology 37, 61-65.
Liu, W.-T., Marsh, T.L., Cheng, H., Forney, L.J., 1997. Characterization of microbial diversity by determining terminal restriction fragment length polymorphisms of genes encoding 16S rRNA. Applied and Environmental Microbiology 63, 4516-4522.
Lu, W.-D., Li, A.-X., Guo, Q.-L., 2014. Production of novel alkalitolerant and thermostable inulinase from marine actinomycete Nocardiopsis sp. DN-K15 and inulin hydrolysis by the enzyme. Annals of Microbiology 64, 441-449.
Ma, Y., Xu, M., Liu, H., Yu, T., Guo, P., Liu, W., Jin, X., 2021. Antimicrobial compounds were isolated from the secondary metabolites of Gordonia, a resident of intestinal tract of Periplaneta americana. AMB Express 11, 1-11.
MacKenzie, C.R., Bilous, D., Schneider, H., Johnson, K.G., 1987. Induction of cellulolytic and xylanolytic enzyme systems in Streptomyces spp. Applied and Environmental Microbiology 53, 2835-2839.
Mahapatra, G.P., Raman, S., Nayak, S., Gouda, S., Das, G., Patra, J.K., 2020. Metagenomics approaches in discovery and development of new bioactive compounds from marine actinomycetes. Current Microbiology 77, 645-656.
Malathi, S., Mohana Priya, D., Palani, P., 2014. Optimization of protease enzyme production by the halo-tolerant Vibrio alginolyticus isolated from marine sources. Microbial Diversity and Biotechnology in Food Security. Springer, pp. 451-462.
Mangamuri, U.K., Vijayalakshmi, M., Poda, S., Manavathi, B., Chitturi, B., Yenamandra, V., 2016. Isolation and biological evaluation of N- (4-aminocyclooctyl)-3, 5-dinitrobenzamide, a new semisynthetic derivative from the Mangrove-associated actinomycete Pseudonocardia endophytica VUK-10. 3 Biotech 6, 1-12.
Manikandan, P., Senthilkumar, P.K., 2017. An overview of saltpan halophilic bacterium. J. Antimicrob. Agents 3, 2472-1212.1000151.
Manteca, Á., Yagüe, P., 2019. Streptomyces as a source of antimicrobials: Novel approaches to activate cryptic secondary metabolite pathways. Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods, 119.
Martín, S., Márquez, M., Sánchez-Porro, C., Mellado, E., Arahal, D., Ventosa, A., 2003. Marinobacter lipolyticus sp. nov., a novel moderate halophile with lipolytic activity. International Journal of Systematic and Evolutionary Microbiology 53, 1383-1387.
Martínez, M.-A., Ares, I., Martínez, M., Lopez-Torres, B., Rodríguez, J.-L., Maximiliano, J.-E., Martínez-Larrañaga, M.-R., Anadón, A., de la Rosa, J.-M., Cueto, M., 2020. Protective effects of culture extracts (CB08035-SCA and CB08035-SYP) from Marinobacter hydrocarbonoclasticus (strain CB08035) against oxidant-induced stress in human colon carcinoma Caco-2 cells. Food and Chemical Toxicology 145, 111671.
Massey, I.Y., Yang, F., 2020. A mini review on microcystins and bacterial degradation. Toxins 12, 268.
Meerloo, J.V., Kaspers, G.J., Cloos, J., 2011. Cell sensitivity assays: the MTT assay. Cancer cell culture. Springer, pp. 237-245.
Mhandi, N.B., 2020. Halophilic bacteria and their biomolecules: Recent advances and future applications in biomedicine. Moroccan Journal of Agricultural Sciences 1.
Namwong, S., Tanasupawat, S., Visessanguan, W., Kudo, T., Itoh, T., 2007. Halococcus thailandensis sp. nov., from fish sauce in Thailand. International Journal of Systematic and Evolutionary Microbiology 57, 2199-2203.
Negri, A., Webster, N., Hill, R., Heyward, A., 2001. Metamorphosis of broadcast spawning corals in response to bacteria isolated from crustose algae. Marine Ecology Progress Series 223, 121-131.
Nei, M., Kumar, S., 2000. Molecular evolution and phylogenetics. Oxford University Press, USA.
Nigam, P.S., 2013. Microbial enzymes with special characteristics for biotechnological applications. Biomolecules 3, 597-611.
Osko, J.D., Roose, B.W., Shinsky, S.A., Christianson, D.W., 2019. Structure and function of the acetylpolyamine amidohydrolase from the deep earth halophile Marinobacter subterrani. Biochemistry 58, 3755-3766.
Palma, L., Muñoz, D., Berry, C., Murillo, J., Caballero, P., 2014. Bacillus thuringiensis toxins: an overview of their biocidal activity. Toxins 6, 3296-3325.
Pang, Z., Raudonis, R., Glick, B.R., Lin, T.-J., Cheng, Z., 2019. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnology Advances 37, 177-192.
Peng, L.-H., Liang, X., Xu, J.-K., Dobretsov, S., Yang, J.-L., 2020. Monospecific biofilms of Pseudoalteromonas promote larval settlement and metamorphosis of Mytilus coruscus. Scientific Reports 10, 1-12.
Pernthaler, A., Pernthaler, J., Amann, R., 2002. Fluorescence in situ hybridization and catalyzed reporter deposition for the identification of marine bacteria. Applied and Environmental Microbiology 68, 3094-3101.
Peters, L., Olson, L., Khu, D.T., Linnros, S., Le, N.K., Hanberger, H., Hoang, N.T., Tran, D.M., Larsson, M., 2019. Multiple antibiotic resistance as a risk factor for mortality and prolonged hospital stay: a cohort study among neonatal intensive care patients with hospital-acquired infections caused by gram-negative bacteria in Vietnam. PLOS ONE 14, e0215666.
Peters, S., Koschinsky, S., Schwieger, F., Tebbe, C.C., 2000. Succession of microbial communities during hot composting as detected by PCR– single- strand-conformation polymorphism-based genetic profiles of small-subunit rRNA genes. Applied and Environmental Microbiology 66, 930-936.
Phrommao, E., Rodtong, S., Yongsawatdigul, J., 2011. Identification of novel halotolerant bacillopeptidase F‐like proteinases from a moderately halophilic bacterium, Virgibacillus sp. SK37. Journal of Applied Microbiology 110, 191-201.
Ramanan, P., Deziel, P.J., Wengenack, N.L., 2013. Gordonia bacteremia. Journal of Clinical Microbiology 51, 3443-3447.
Ramesh, C., Vinithkumar, N.V., Kirubagaran, R., 2019. Marine pigmented bacteria: A prospective source of antibacterial compounds. Journal of Natural Science Biology and Medicine 10: 104-113
Rodriguez Jimenez, A., Dechamps, E., Giaux, A., Goetghebuer, L., Bauwens, M., Willenz, P., Flahaut, S., Laport, M.S., George, I.F., 2021. The sponges Hymeniacidon perlevis and Halichondria panicea are reservoirs of antibiotic‐ producing bacteria against multi‐drug resistant Staphylococcus aureus. Journal of Applied Microbiology 131, 706-718.
Rodríguez-Sáiz, M., Sánchez-Porro, C., De La Fuente, J.L., Mellado, E., Barredo, J.L., 2007. Engineering the halophilic bacterium Halomonas elongata to produce β-carotene. Applied Microbiology and Biotechnology 77, 637-643.
Rodriguez-Valera, F., Juez, G., Kushner, D., 1982. Halocins: salt-dependent bacteriocins produced by extremely halophilic rods. Canadian Journal of Microbiology 28, 151-154.
Sadeghpour Heravi, F., Zakrzewski, M., Vickery, K., G. Armstrong, D., Hu, H., 2019. Bacterial diversity of diabetic foot ulcers: current status and future prospectives. Journal of Clinical Medicine 8, 1935.
Saitou, N., Nei, M., 1987. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Molecular Biology and Evolution 4, 406-425.
Santhaseelan, H., Dinakaran, V.T., Dahms, H.-U., Ahamed, J.M., Murugaiah, S.G., Krishnan, M., Hwang, J.-S., Rathinam, A.J., 2022. Recent antimicrobial responses of halophilic microbes in clinical pathogens. Microorganisms 10, 417.
Saravanan, M., Barik, S.K., MubarakAli, D., Prakash, P., Pugazhendhi, A., 2018. Synthesis of silver nanoparticles from Bacillus brevis (NCIM 2533) and their antibacterial activity against pathogenic bacteria. Microbial Pathogenesis 116, 221-226.
Sarhan, D., Shehata, R., Kandil, Y., Kotb, M., El-Bassiouni, E., 2016. Influence of whole body x-irradiation on the liver and possible protective effect by the compatible solute ectoine in a mouse model. Eur J Biophys 4, 16-21.
Sarilmiser, H.K., Oner, E.T., 2014. Investigation of anti-cancer activity of linear and aldehyde-activated levan from Halomonas smyrnensis AAD6T. Biochemical Engineering Journal 92, 28-34.
Sato, M., Beppu, T., Arima, K., 1983. Studies on antibiotics produced at high alkaline pH. Agricultural and Biological Chemistry 47, 2019-2027.
Schloss, P.D., Westcott, S.L., Ryabin, T., Hall, J.R., Hartmann, M., Hollister, E.B., Lesniewski, R.A., Oakley, B.B., Parks, D.H., Robinson, C.J., 2009. Introducing mothur: open-source, platform-independent, community- supported software for describing and comparing microbial communities. Applied and Environmental Microbiology 75, 7537-7541.
Schröter, M.-A., Meyer, S., Hahn, M.B., Solomun, T., Sturm, H., Kunte, H.-J., 2017. Ectoine protects DNA from damage by ionizing radiation. Scientific Reports 7, 1-7.
Selvarajan, R., Sibanda, T., Tekere, M., Nyoni, H., Meddows-Taylor, S., 2017. Diversity analysis and bioresource characterization of halophilic bacteria isolated from a South African saltpan. Molecules 22, 657.
Shannon, C.E., 1949. The mathematical theory of communication, by CE Shannon (and recent contributions to the mathematical theory of communication), W. Weaver. University of Illinois Press Champaign, IL, USA.
Sharma, G., Dang, S., Gupta, S., Gabrani, R., 2018. Antibacterial activity, cytotoxicity, and the mechanism of action of bacteriocin from Bacillus subtilis GAS101. Medical Principles and Practice 27, 186-192.
Shieh, W.Y., 1993. A halophilic thermophilic bacterium isolated from a coastal hot spring in Lutao, Taiwan. Microbiology 139, 2505-2510.
Shivanand, P., Mugeraya, G., 2011. Halophilic bacteria and their compatible solutes–osmoregulation and potential applications. Current Science, 1516- 1521.
Shnit-Orland, M., Sivan, A., Kushmaro, A., 2012. Antibacterial activity of Pseudoalteromonas in the coral holobiont. Microbial Ecology 64, 851-859.
Simpson, E.H., 1949. Measurement of diversity. Nature 163, 688-688.
Sivalingam, P., Hong, K., Pote, J., Prabakar, K., 2019. Extreme environment Streptomyces: potential sources for new antibacterial and anticancer drug leads? International Journal of Microbiology 2019.
Sowani, H., Kulkarni, M., Zinjarde, S., 2018. An insight into the ecology, diversity and adaptations of Gordonia species. Critical Reviews in Microbiology 44, 393-413.
Sowani, H., Mohite, P., Munot, H., Shouche, Y., Bapat, T., Kumar, A.R., Kulkarni, M., Zinjarde, S., 2016. Green synthesis of gold and silver nanoparticles by an actinomycete Gordonia amicalis HS-11: mechanistic aspects and biological application. Process Biochemistry 51, 374-383.
Srivastava, P., Kowshik, M., 2016. Anti-neoplastic selenium nanoparticles from Idiomarina sp. PR58-8. Enzyme and Microbial Technology 95, 192-200.
Su, J., Yang, X., Zhou, Y., Zheng, T., 2011. Marine bacteria antagonistic to the harmful algal bloom species Alexandrium tamarense (Dinophyceae). Biological Control 56, 132-138.
Suginta, W., Robertson, P., Austin, B., Fry, S.C., Fothergill‐Gilmore, L.A., 2000. Chitinases from Vibrio: activity screening and purification of chiA from Vibrio carchariae. Journal of Applied Microbiology 89, 76-84.
Ta-Chen, L., Chang, J.-S., Young, C.-C., 2008. Exopolysaccharides produced by Gordonia alkanivorans enhance bacterial degradation activity for diesel. Biotechnology Letters 30, 1201-1206.
Tatar, D., 2021. Isolation, phylogenetic analysis and antimicrobial activity of halophilic actinomycetes from different saline environments located near Çorum province. Biologia 76, 773-780.
Thompson, J.D., Higgins, D.G., Gibson, T.J., 1994. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Research 22, 4673-4680.
Thongthai, C., McGenity, T.J., Suntinanalert, P., Grant, W.D., 1992. Isolation and characterization of an extremely halophilic archaeobacterium from traditionally fermented Thai fish sauce (nam pla). Letters in applied microbiology 14, 111-114.
Tian, S., Yang, Y., Liu, K., Xiong, Z., Xu, L., Zhao, L., 2014. Antimicrobial metabolites from a novel halophilic actinomycete Nocardiopsis terrae YIM 90022. Natural Product Research 28, 344-346.
Toopcham, T., Mes, J.J., Wichers, H.J., Yongsawatdigul, J., 2017. Immunomodulatory activity of protein hydrolysates derived from Virgibacillus halodenitrificans SK1-3-7 proteinase. Food Chemistry 224, 320-328.
Trejo-Estrada, S., Paszczynski, A., Crawford, D., 1998. Antibiotics and enzymes produced by the biocontrol agent Streptomyces violaceusniger YCED-9. Journal of Industrial Microbiology and Biotechnology 21, 81-90.
Tseng, W.-P., Chen, Y.-C., Chen, S.-Y., Chen, S.-Y., Chang, S.-C., 2018. Risk for subsequent infection and mortality after hospitalization among patients with multidrug-resistant gram-negative bacteria colonization or infection. Antimicrobial Resistance & Infection Control 7, 1-12.
Umadevi, K., Krishnaveni, M., 2013. Antibacterial activity of pigment produced from Micrococcus luteus KF532949. International Journal of Chemical and Analytical Science 4, 149-152.
van Elsas, J.D., Costa, R., Jansson, J., Sjöling, S., Bailey, M., Nalin, R., Vogel, T.M., van Overbeek, L., 2008. The metagenomics of disease-suppressive soils– experiences from the METACONTROL project. Trends in Biotechnology 26, 591-601.
Vazquez-Dominguez, E., Casamayor, E.O., Catala, P., Lebaron, P., 2005. Different marine heterotrophic nanoflagellates affect differentially the composition of enriched bacterial communities. Microbial Ecology 49, 474-485.
Ventosa, A., de la Haba, R.R., Sánchez-Porro, C., Papke, R.T., 2015. Microbial diversity of hypersaline environments: a metagenomic approach. Current Opinion in Microbiology 25, 80-87.
Vurukonda, S.S.K.P., Giovanardi, D., Stefani, E., 2018. Plant growth promoting and biocontrol activity of Streptomyces spp. as endophytes. International Journal of Molecular Sciences 19, 952.
Wang, C., Wang, Z., Qiao, X., Li, Z., Li, F., Chen, M., Wang, Y., Huang, Y., Cui, H., 2013. Antifungal activity of volatile organic compounds from Streptomyces alboflavus TD-1. FEMS Microbiology Letters 341, 45-51.
Wang, C.-Y., Chang, C.-C., Ng, C.C., Chen, T.-W., Shyu, Y.-T., 2008. Virgibacillus chiguensis sp. nov., a novel halophilic bacterium isolated from Chigu, a previously commercial saltern located in southern Taiwan. International Journal of Systematic and Evolutionary Microbiology 58, 341-345.
Wang, Q., Wei, M., Zhang, J., Yue, Y., Wu, N., Geng, L., Sun, C., Zhang, Q., Wang, J., 2021. Structural characteristics and immune-enhancing activity of an extracellular polysaccharide produced by marine Halomonas sp. 2E1. International Journal of Biological Macromolecules 183, 1660-1668.
Wang, Z., Fu, P., Liu, P., Wang, P., Hou, J., Li, W., Zhu, W., 2013. New pyran‐2‐ones from alkalophilic actinomycete, Nocardiopsis alkaliphila sp. Nov. YIM‐80379. Chemistry & Biodiversity 10, 281-287.
Whitman, W.B., Coleman, D.C., Wiebe, W.J., 1998. Prokaryotes: the unseen majority. Proceedings of the National Academy of Sciences of the United States of America 95, 6578-6583.
Wu, Y., Zhou, J., Li, C., Ma, Y., 2019. Antifungal and plant growth promotion activity of volatile organic compounds produced by Bacillus amyloliquefaciens. MicrobiologyOpen 8, e00813.
Xu, H.-S., Roberts, N., Singleton, F., Attwell, R., Grimes, D.J., Colwell, R., 1982. Survival and viability of nonculturable Escherichia coli and Vibrio cholerae in the estuarine and marine environment. Microbial Ecology 8, 313-323.
Xu, Y., Liu, Y., Xu, B., Wang, D., Jiang, W., 2016. Characterisation and application of Halomonas shantousis SWA25, a halotolerant bacterium with multiple biogenic amine degradation activity. Food Additives & Contaminants: Part A 33, 674-682.
Xu, Z., Shao, J., Li, B., Yan, X., Shen, Q., Zhang, R., 2013. Contribution of bacillomycin D in Bacillus amyloliquefaciens SQR9 to antifungal activity and biofilm formation. Applied and Environmental Microbiology 79, 808-815.
Yakimov, M.M., Timmis, K.N., Golyshin, P.N., 2007. Obligate oil-degrading marine bacteria. Current Opinion in Biotechnology 18, 257-266.
Yang, C., Wang, X., Miao, F., Li, Z., Tang, W., Sun, J., 2020. Assessing the effect of soil salinization on soil microbial respiration and diversities under incubation conditions. Applied Soil Ecology 155, 103671.
Yoo, W., Kim, B., Jeon, S., Kim, K.K., Kim, T.D., 2020. Identification, characterization, and immobilization of a novel YbfF esterase from Halomonas elongata. International Journal of Biological Macromolecules 165, 1139-1148.
Zhang, H., Li, H., Lang, D.A., Xu, H., Zhu, H., 2018. Purification, characterization and potential applications of a novel halotolerant metalloprotease from marine bacterium Vibrio sp. LA‐05. Journal of Chemical Technology & Biotechnology 93, 3627-3637.
Zhang, H., Ma, B., Huang, T., Shi, Y., 2021. Nitrate reduction by the aerobic denitrifying actinomycete Streptomyces sp. XD-11-6-2: Performance, metabolic activity, and micro-polluted water treatment. Bioresource Technology 326, 124779.
Zhang, J.-W., Zeng, R.-Y., 2008. Purification and characterization of a cold-adapted α-amylase produced by Nocardiopsis sp. 7326 isolated from Prydz Bay, Antarctic. Marine Biotechnology 10, 75-82.
Zhao, J., Han, L., Yu, M., Cao, P., Li, D., Guo, X., Liu, Y., Wang, X., Xiang, W., 2019. Characterization of Streptomyces sporangiiformans sp. nov., a novel soil actinomycete with antibacterial activity against Ralstonia solanacearum. Microorganisms 7, 360.
Zheng, W., Chen, C., Cheng, Q., Wang, Y., Chu, C., 2006. Oral administration of exopolysaccharide from Aphanothece halophytica (Chroococcales) significantly inhibits influenza virus (H1N1)-induced pneumonia in mice. International Immunopharmacology 6, 1093-1099.
Zhou, C., Qin, H., Chen, X., Zhang, Y., Xue, Y., Ma, Y., 2018. A novel alkaline protease from alkaliphilic Idiomarina sp. C9-1 with potential application for eco-friendly enzymatic dehairing in the leather industry. Scientific Reports 8, 1-18.
Zolfaghar, M., Amoozegar, M.A., Khajeh, K., Babavalian, H., Tebyanian, H., 2019. Isolation and screening of extracellular anticancer enzymes from halophilic and halotolerant bacteria from different saline environments in Iran. Molecular Biology Reports 46, 3275-3286.