Bioactive Metabolites Isolated from Microorganisms for Healthcare: Types and Delivery Routes

  • Debashish Mohanta
  • S. Maneesha
  • Rajesh Ghangal
  • Manu Solanki
  • Soma PatnaikEmail author
Part of the Environmental Chemistry for a Sustainable World book series (ECSW, volume 28)


Microbial bioactive compounds are one of the most raw forms of chemical metabolites present in nature. Essentially, these compounds play an important role in establishing inter-kingdom interactions. In the last few decades, researchers have explored many types of microbes for bioactive metabolites having pharmacological properties. Microorganisms are known as the potential source for antioxidants, vitamins, antibiotics and enzymes. The number of microbial metabolites being isolated and screened for the treatment of human diseases has increased manifolds. With the development of high-throughput techniques, the quality and quantity of microbial metabolites being tested has also grown rapidly. There are reports suggesting that microbial metabolites are more reliable in terms of efficacy and potential when compared to its chemical counterparts for curing human diseases.

This chapter discusses microbial isolates having antidiabetic, anticancerous, antibacterial, and antifungal properties. Different strains of marine bacteria and fungi have been used to isolate metabolites exhibiting anticancerous properties. Micromonospora marina is one of the extensively studied microbes for isolating anticancerous metabolites. Some microbial metabolites are known for their antifungal properties. In the early 1970s, echinocandin B extracted from Aspergillus nidulans was reported to have antifungal property, thereby opening up avenues for the screening of more such metabolites to cure human diseases. Due to the involvement of advanced automated equipments, it is easier to screen a large number of compounds for their pharmacological examination in in vitro conditions. However, the major challenge happens to be the delivery of these bioactive compounds in in vivo conditions. Indeed, the biological barriers in the body restrict the delivery of drugs in in vivo conditions. Since these bioactive compounds are more labile than the chemically synthesized constituents of drugs, it becomes a challenge for these compounds to reach its target site without getting degraded in the metabolic processes. The chapter discusses the three most patient-friendly delivery routes, i.e., oral, intravenous, and intradermal. Since the major share of drugs consumed is in the form of oral dosage, the chemical compounds have been categorized into four classes under the “biopharmaceutical classification system.”


Bioactive compounds Antidiabetic Anticancerous Antibacterial Antifungal Delivery Oral Intravenous Intradermal Nanoparticles Encapsulation Liposomes 


  1. Aftab U, Zechel DL, Sajid I (2015) Antitumor compounds from Streptomyces sp. KML-2, isolated from Khewra salt mines, Pakistan. Biol Res 48:58. CrossRefGoogle Scholar
  2. Al-Zereini WA (2014) Bioactive crude extracts from four bacterial isolates of marine sediments from Red Sea, Gulf of Aqaba, Jordan. Jordan J Biol Sci 7:133–137. CrossRefGoogle Scholar
  3. Anal AK (2007) Time-controlled pulsatile delivery systems for bioactive compounds. Recent Pat Drug Deliv Formul 1:73–79. CrossRefGoogle Scholar
  4. Andayani DG, Sukandar U, Sukandar EY, Adnyana IK (2015) Antibacterial, antifungal and anticancer activity of five strains of soil microorganisms isolated from Tangkuban Perahu Mountain by fermentation. HAYATI J Biosci 22:186–190. CrossRefGoogle Scholar
  5. Arakaki AK, Mezencev R, Bowen NJ, Huang Y, McDonald JF, Skolnick J (2008) Identification of metabolites with anticancer properties by computational metabolomics. Mol Cancer 7:57. CrossRefGoogle Scholar
  6. Awati A, Konstantinov SR, Williams BA, Akkermans AD, Bosch MW, Smidt H, Verstegen MW (2005) Effect of substrate adaptation on the microbial fermentation and microbial composition of faecal microbiota of weaning piglets studied in vitro. J Sci Food Agric 85:1765–1772. CrossRefGoogle Scholar
  7. Bhattacharjee R, Mitra A, Dey B, Pal A (2014) Exploration of anti-diabetic potentials amongst marine species-a mini review. Indo Glob J Pharm Sci 4:65–73Google Scholar
  8. Braga RM, Dourado MN, Araújo WL (2016) Microbial interactions: ecology in a molecular perspective. Braz J Microbiol 47:86–98. CrossRefGoogle Scholar
  9. Brandon EF, Sparidans RW, van Ooijen RD, Meijerman I, Lazaro LL, Manzanares I, Beijnen JH, Schellens JH (2007) In vitro characterization of the human biotransformation pathways of aplidine, a novel marine anti-cancer drug. Investig New Drugs 25:9–19. CrossRefGoogle Scholar
  10. Broggini M, Marchini SV, Galliera E, Borsotti P, Taraboletti G, Erba E, Sironi M, Jimeno J, Faircloth GT, Giavazzi R, d’Incalci M (2003) Aplidine, a new anticancer agent of marine origin, inhibits vascular endothelial growth factor (VEGF) secretion and blocks VEGF-VEGFR-1 (flt-1) autocrine loop in human leukemia cells MOLT-4. Leukemia 17:52. CrossRefGoogle Scholar
  11. Bruggink A, Roos EC, de Vroom E (1998) Penicillin acylase in the industrial production of β-lactam antibiotics. Org Process Res Dev 2:128–133. CrossRefGoogle Scholar
  12. Cai X, Fang Z, Dou J, Yu A, Zhai G (2013) Bioavailability of quercetin: problems and promises. Curr Med Chem 20:2572–2582. CrossRefGoogle Scholar
  13. Cannell RJ, Kellam SJ, Owsianka AM, Walker JM (1987) Microalgae and cyanobacteria as a source of glycosidase inhibitors. Microbiology 133:1701–1705. CrossRefGoogle Scholar
  14. Cardot JM, Arieta AG, Paixao P, Tasevska I, Davit B (2016) Implementing the biopharmaceutics classification system in drug development: reconciling similarities, differences, and shared challenges in the EMA and US-FDA-recommended approaches. AAPS J 18:1039–1046. CrossRefGoogle Scholar
  15. Carter NJ, Keam SJ (2007) Trabectedin: a review of its use in the management of soft tissue sarcoma and ovarian cancer. Drugs 67:2257–2276. CrossRefGoogle Scholar
  16. Charyulu EM, Sekaran G, Rajakumar GS, Gnanamani A (2009) Antimicrobial activity of secondary metabolite from marine isolate, Pseudomonas sp. against Gram positive and negative bacteria including MRSA. Indian J Exp Biol 47:964–968 Google Scholar
  17. Chuang SY, Lin CH, Huang TH, Fang JY (2018) Lipid-based nanoparticles as a potential delivery approach in the treatment of rheumatoid arthritis. J Nanomater 8(1):42. CrossRefGoogle Scholar
  18. Cornara L, Biagi M, Xiao J, Burlando B (2017) Therapeutic properties of bioactive compounds from different honeybee products. Front Pharmacol 8:412. CrossRefGoogle Scholar
  19. Cragg GM, Newman DJ (2013) Natural products: a continuing source of novel drug leads. Biochim Biophys Acta 1830:3670–3695. CrossRefGoogle Scholar
  20. Darabpour E, Ardakani MR, Motamedi H, Ronagh MT (2012) Isolation of a potent antibiotic producer bacterium, especially against MRSA, from northern region of the Persian Gulf. Bosn J Basic Med Sci 12:108–121. CrossRefGoogle Scholar
  21. De la Monte SM, Wands JR (2008) Alzheimer’s disease is type 3 diabetes—evidence reviewed. J Diabetes Sci Technol 2(6):1101–1113CrossRefGoogle Scholar
  22. Debbab A, Aly AH, Lin WH, Proksch P (2010) Bioactive compounds from marine bacteria and fungi. Microb Biotechnol 3:544–563. CrossRefGoogle Scholar
  23. Demain AL, Sanchez S (2009) Microbial drug discovery: 80 years of progress. J Antibiot 62:5–16. CrossRefGoogle Scholar
  24. Desjardine K, Pereira A, Wright H, Matainaho T, Kelly M, Andersen RJ (2007) Tauramamide, a lipopeptide antibiotic produced in culture by Brevibacilluslaterosporus isolated from a marine habitat: structure elucidation and synthesis. J Nat Prod 70:1850–1853. CrossRefGoogle Scholar
  25. Dompeipen EJ, Srikandace Y, Suharso WP, Cahyana H, Simanjuntak P (2011) Potential endophytic microbes selection for antidiabetic bioactive compounds production. Asian J Biochem 6:465–471. CrossRefGoogle Scholar
  26. Donnelly RF, Singh TR, Garland MJ, Migalska K, Majithiya R, McCrudden CM, Kole PL, Mahmood TM, McCarthy HO, Woolfson AD (2012) Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery. Adv Funct Mater 22:4879–4890. CrossRefGoogle Scholar
  27. Donnelly RF, Moffatt K, Alkilani AZ, Vicente-Pérez EM, Barry J, McCrudden MT, Woolfson AD (2014) Hydrogel-forming microneedle arrays can be effectively inserted in skin by self-application: a pilot study centred on pharmacist intervention and a patient information leaflet. Pharm Res 31:1989–1999. CrossRefGoogle Scholar
  28. Dyshlovoy SA, Fedorov SN, Shubina LK, Kuzmich AS, Bokemeyer C, Keller-von Amsberg G, Honecker F (2014) Aaptamines from the Marine Sponge Aaptos sp. display anticancer activities in human cancer cell lines and modulate AP-1-, NF-κB-, and p53-dependent transcriptional activity in mouse JB6 Cl41 Cells. Biomed Res Int 2014:469309. CrossRefGoogle Scholar
  29. Edmond MB, Ober JF, Weinbaum DL, Pfaller MA, Hwang T, Sanford MD, Wenzel RP (1995) Vancomycin-resistant Enterococcus faecium bacteremia: risk factors for infection. Clin Infect Dis 20:1126–1133. CrossRefGoogle Scholar
  30. Feng X, Li DP, Zhang ZS, Chu ZY, Luan J (2014) Microbial transformation of the anti-diabetic agent corosolic acid. Nat Prod Res 28:1879–1886. CrossRefGoogle Scholar
  31. Feng X, Lu YH, Liu Z, Li DP, Zou YX, Fang YQ, Chu ZY (2017) Microbial transformation of the anti-diabetic agent corosolic acid by Cunninghamella echinulata. J Asian Nat Prod Res 19:645–650. CrossRefGoogle Scholar
  32. Fleming A (1929) On the antibacterial action of cultures of a Penicillium with special reference to their use in the isolation of B. influenzae. Br J ExpPathol 10:226–236Google Scholar
  33. Fukuda T, Naka W, Tajima S, Nishikawa T (1996) Neutral red assay in minimum fungicidal concentrations of antifungal agents. J Med Vet Mycol 34:353–356. CrossRefGoogle Scholar
  34. Gao ZM, Wang Y, Lee OO, Tian RM, Wong YH, Bougouffa S, Batang Z, Al-Suwailem A, Lafi FF, Bajic VB, Qian PY (2014) Pyrosequencing reveals the microbial communities in the Red Sea sponge Carteriospongiafoliascens and their impressive shifts in abnormal tissues. Microb Ecol 68:621–632. CrossRefGoogle Scholar
  35. Gaskins HR (2001) Intestinal bacteria and their influence on swine growth. In: Lewis AJ, Southern LL (eds) Swine nutrition. Taylor and Francis, Boca Roca, pp 585–608Google Scholar
  36. Gennigens C, Jerusalem G (2011) Trabectedin (ET-743/Yondelis) for treating soft tissue sarcomas and ovarian cancer. Rev Med Liege 66:452–455Google Scholar
  37. Georgopapadakou NH, Walsh TJ (1994) Human mycoses: drugs and targets for emerging pathogens. Science 264:371–374. CrossRefGoogle Scholar
  38. Gibson GR, Roberfroid MB (1995) Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 125:1401–1412CrossRefGoogle Scholar
  39. Gibson GR, Probert HM, Van Loo J, Rastall RA, Roberfroid MB (2004) Dietary modulation of the human colonic microbiota: updating the concept of prebiotics. Nutr Res Rev 17:259–275. CrossRefGoogle Scholar
  40. Gouda S, Das G, Sen SK, Shin HS, Patra JK (2016) Endophytes: a treasure house of bioactive compounds of medicinal importance. Front Microbiol 7:1538. CrossRefGoogle Scholar
  41. Gupta C, Prakash D, Gupta S (2014a) Natural useful therapeutic products from microbes. J Microbiol Exp 1:00006. CrossRefGoogle Scholar
  42. Gupta C, Prakash D, Garg AP, Gupta S (2014b) Nutraceuticals from microbes. In: Prakash G, Sharma G (eds) Phytochemicals of nutraceutical importance. CABI International Publishers, Wallingford, pp 79–102. CrossRefGoogle Scholar
  43. Heidarpour F, Mohammadabadi MR, Zaidul IS, Maherani B, Saari N, Hamid AA, Abas F, Manap MY, Mozafari MR (2011) Use of prebiotics in oral delivery of bioactive compounds: a nanotechnology perspective. Pharmazie 66:319–324. CrossRefGoogle Scholar
  44. Holmström C, Kjelleberg S (1999) Marine Pseudoalteromonas species are associated with higher organisms and produce biologically active extracellular agents. FEMS Microbiol Ecol 30:285–293. CrossRefGoogle Scholar
  45. Huq T, Khan A, Khan RA, Riedl B, Lacroix M (2013) Encapsulation of probiotic bacteria in biopolymeric system. Crit Rev Food Sci Nutr 53(9):909–916. CrossRefGoogle Scholar
  46. Hutin Y, Hauri A, Chiarello L, Catlin M, Stilwell B, Ghebrehiwet T, Garner J (2003) Best infection control practices for intradermal, subcutaneous, and intramuscular needle injections. Bull World Health Organ 81:491–500Google Scholar
  47. Imada C (2005) Enzyme inhibitors and other bioactive compounds from marine actinomycetes. Antonie Van Leeuwenhoek 87:59–63. CrossRefGoogle Scholar
  48. Indermun S, Luttge R, Choonara YE, Kumar P, Du Toit LC, Modi G, Pillay V (2014) Current advances in the fabrication of microneedles for transdermal delivery. J Control Release 185:130–138. CrossRefGoogle Scholar
  49. Isnansetyo A, Kamei Y (2003) Pseudoalteromonas phenolica sp. nov., a novel marine bacterium that produces phenolic anti-methicillin-resistant Staphylococcus aureus substances. Int J Syst Evol Microbiol 53:583–588. CrossRefGoogle Scholar
  50. James HP, John R, Alex A, Anoop KR (2014) Smart polymers for the controlled delivery of drugs–a concise overview. Acta Pharm Sin B 4:120–127. CrossRefGoogle Scholar
  51. Johnstone RW, Ruefli AA, Lowe SW (2002) Apoptosis: a link between cancer genetics and chemotherapy. Cell 108:153–164. CrossRefGoogle Scholar
  52. Jouda JB, Tamokou JD, Mbazoa CD, Sarkar P, Bag PK, Wandji J (2016) Anticancer and antibacterial secondary metabolites from the endophytic fungus Penicillium sp. CAM64 against multi-drug resistant gram-negative bacteria. Afr Health Sci 16:734–743. CrossRefGoogle Scholar
  53. Kalia VC (2017) The dawn of the era of bioactive compounds. In: Kalia V, Saini A (eds) Metabolic engineering for bioactive compounds. Springer, Singapore, pp 3–10. CrossRefGoogle Scholar
  54. Kalimuthu S, Se-Kwon K (2013) Cell survival and apoptosis signaling as therapeutic target for cancer: marine bioactive compounds. Int J Mol Sci 14:2334–2354. CrossRefGoogle Scholar
  55. Kalinovskaya NI, Romanenko LA, Irisawa T, Ermakova SP, Kalinovsky AI (2011) Marine isolate Citricoccus sp. KMM 3890 as a source of a cyclic siderophorenocardamine with antitumor activity. Microbiol Res 166:654–661. CrossRefGoogle Scholar
  56. Kandimalla R, Thirumala V, Reddy PH (2017) Is Alzheimer’s disease a type 3 diabetes? A critical appraisal. Biochimicaet Biophys Acta (BBA)-Mol Basis Dis 1863(5):1078–1089CrossRefGoogle Scholar
  57. Keefer LM, Piron MA, De Meyts P (1981) Human insulin prepared by recombinant DNA techniques and native human insulin interact identically with insulin receptors. Proc Natl Acad Sci USA 78:1391–1395CrossRefGoogle Scholar
  58. Kelly G (2008) Inulin-type prebiotics–a review: part I. Altern Med Rev 13:315–329Google Scholar
  59. Khan I, Saeed K, Khan I (2017) Nanoparticles: properties, applications and toxicities. Arab J Chem.
  60. Kikuchi A, Okano T (2002) Pulsatile drug release control using hydrogels. Adv Drug Deliv Rev 54:53–77. CrossRefGoogle Scholar
  61. Kim YC, Park JH, Prausnitz MR (2012) Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev 64:1547–1568. CrossRefGoogle Scholar
  62. Konstantinov SR, Favier CF, Zhu WY, Williams BA, Klüß J, Souffrant WB, de Vos WM, Akkermans AD, Smidt H (2004) Microbial diversity studies of the porcine gastrointestinal ecosystem during weaning transition. Anim Res 53:317–324. CrossRefGoogle Scholar
  63. Kulkarni-Almeida AA, Brahma MK, Padmanabhan P, Mishra PD, Parab RR, Gaikwad NV, Thakkar CS, Tokdar P, Ranadive PV, Nair AS, Damre AA (2011) Fermentation, isolation, structure, and antidiabetic activity of NFAT-133 produced by Streptomyces strain PM0324667. AMB Express 1:42. CrossRefGoogle Scholar
  64. Kuno T, Tsukamoto T, Hara A, Tanaka T (2012) Cancer chemoprevention through the induction of apoptosis by natural compounds. J Biophys Chem 3:156. CrossRefGoogle Scholar
  65. Kushwaha SK, Saxena P, Rai AK (2012) Stimuli sensitive hydrogels for ophthalmic drug delivery: a review. Int J Pharm Investig 2:54–60. CrossRefGoogle Scholar
  66. Lahlou M (2013) The success of natural products in drug discovery. Pharmacol Pharm 4:17–31. CrossRefGoogle Scholar
  67. Larraneta E, Lutton RE, Woolfson AD, Donnelly RF (2016) Microneedle arrays as transdermal and intradermal drug delivery systems: materials science, manufacture and commercial development. Mater Sci Eng R Rep 104:1–32. CrossRefGoogle Scholar
  68. Leclercq R (2009) Epidemiological and resistance issues in multidrug-resistant Staphylococci and Enterococci. Clin Microbiol Infect 15:224–231. CrossRefGoogle Scholar
  69. Levenfors JJ, Hedman R, Thaning C, Gerhardson B, Welch CJ (2004) Broad-spectrum antifungal metabolites produced by the soil bacterium Serratiaplymuthica A 153. Soil Biol Biochem 36:677–685. CrossRefGoogle Scholar
  70. Lieschke GJ, Currie PD (2007) Animal models of human disease: zebrafish swim into view. Nat Rev Genet 8:353–367. CrossRefGoogle Scholar
  71. Lin A, Wu G, Gu Q, Zhu T, Li D (2014) Neweremophilane-type sesquiterpenes from an Antarctic deep-sea derived fungus, Penicillium sp. PR19 N-1. Arch Pharm Res 37:839–844. CrossRefGoogle Scholar
  72. Lin CH, Chen CH, Lin ZC, Fang JY (2017) Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers. J Food Drug Anal 25:219–234. CrossRefGoogle Scholar
  73. Long AN, Dagogo-Jack S (2011) Comorbidities of diabetes and hypertension: mechanisms and approach to target organ protection. J Clin Hypertens 13:244–251. CrossRefGoogle Scholar
  74. Lucas-Elio P, Hernandez P, Sanchez-Amat A, Solano F (2005) Purification and partial characterization of marinocine, a new broad-spectrum antibacterial protein produced by Marinomonasmediterranea. Biochim Biophys Acta 1721:193–203. CrossRefGoogle Scholar
  75. Majumder P, Banerjee A, Shandilya J, Senapati P, Chatterjee S, Kundu TK, Dasgupta D (2013) Minor groove binder distamycin remodels chromatin but inhibits transcription. PLoS One 8:e57693. CrossRefGoogle Scholar
  76. Makhlof A, Fujimoto S, Tozuka Y, Takeuchi H (2011) In vitro and in vivo evaluation of WGA–carbopol modified liposomes as carriers for oral peptide delivery. Eur J Pharm Biopharm 77:216–224. CrossRefGoogle Scholar
  77. Manivasagan P, Venkatesan J, Sivakumar K, Kim SK (2014) Pharmaceutically active secondary metabolites of marine actinobacteria. Microbiol Res 169:262–278. CrossRefGoogle Scholar
  78. McEvoy GK (1993) AHFS drug information 93. American Society of Hospital Pharmacists, BethesdaGoogle Scholar
  79. McClements DJ, Decker EA, Park Y, Weiss J (2009) Structural design principles for delivery of bioactive components in nutraceuticals and functional foods. Crit Rev Food Sci Nutr 49:577–606. CrossRefGoogle Scholar
  80. Montalvao SIG, Singh V, Haque S (2014) Bioassays for bioactivity screening. Compr Anal Chem 65:79–114. CrossRefGoogle Scholar
  81. Nyfeler R, Keller-Schierlein W (1974) Metabolites of microorganisms. 143. Echinocandin B, a novel polypeptide-antibiotic from Aspergillus nidulans var. echinulatus: isolation and structural components. Helv Chim Acta 57:2459–2477. CrossRefGoogle Scholar
  82. Pandey S, Sree A, Dash SS, Sethi DP, Chowdhury L (2013) Diversity of marine bacteria producing beta-glucosidase inhibitors. Microb Cell Factories 12:5. CrossRefGoogle Scholar
  83. Patel VR, Patel VP (2015) Pulsatile drug delivery system- a review. Int J Pharm Sci Res 6:3676–3688. CrossRefGoogle Scholar
  84. Paul AK, Banerjee AK (1983) A new antifungal antibiotic produced by Streptomyces galbus. Folia Microbiol 28:386–396. CrossRefGoogle Scholar
  85. Paulson DS (2016) Topical antimicrobials: classification and performance. In: Rahmann A (ed) Frontiers in clinical drug research: anti-infectives, 2:137–150.
  86. Porter CJH, Charman WN (1997) Uptake of drugs into the intestinal lymphatics after oral administration. Adv Drug Deliv Rev 25:71–89. CrossRefGoogle Scholar
  87. Prausnitz MR (2004) Microneedles for transdermal drug delivery. Adv Drug Deliv Rev 56:581–587. CrossRefGoogle Scholar
  88. Radjasa OK, Martens T, Grossart HP, Brinkhoff T, Sabdono A, Simon M (2007) Antagonistic activity of a marine bacterium Pseudoalteromonasluteoviolacea TAB4. 2 associated with coral Acropora sp. J Biol Sci 7:239–246. CrossRefGoogle Scholar
  89. Rahman L, Shinwari ZK, Iqrar I, Rahman L, Tanveer F (2017) An assessment on the role of endophytic microbes in the therapeutic potential of Fagoniaindica. Ann Clin Microbiol Antimicrob 16:53. CrossRefGoogle Scholar
  90. Ravikant KT, Gupte S, Kaur M (2015) A review on emerging fungal infections and their significance. J Bacteriol Mycol 1:9–11. CrossRefGoogle Scholar
  91. Romanenko LA, Uchino M, Tebo BM, Tanaka N, Frolova GM, Mikhailov VV (2008) Pseudomonas marincola sp. nov., isolated from marine environments. Int J Syst Evol Microbiol 58:706–710. CrossRefGoogle Scholar
  92. Romero F, Espliego F, Baz JP, De Quesada TG, Grávalos D, De La Calle FE, Fernández-Puentes JL (1997) Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. J Antibiot 50:734–737. CrossRefGoogle Scholar
  93. Sadik CD, Zillikens D (2013) Skin-specific drug delivery: a rapid solution to skin diseases? J Investig Dermatol 133:2135–2137. CrossRefGoogle Scholar
  94. Sagar S, Esau L, Hikmawan T, Antunes A, Holtermann K, Stingl U, Bajic VB, Kaur M (2013a) Cytotoxic and apoptotic evaluations of marine bacteria isolated from brine-seawater interface of the Red Sea. BMC Complement Altern Med 13:29. CrossRefGoogle Scholar
  95. Sagar S, Esau L, Holtermann K, Hikmawan T, Zhang G, Stingl U, Bajic VB, Kaur M (2013b) Induction of apoptosis in cancer cell lines by the Red Sea brine pool bacterial extracts. BMC Complement Altern Med 13:344. CrossRefGoogle Scholar
  96. Sajid I, Shaaban KA, Hasnain S (2011) Identification, isolation and optimization of antifungal metabolites from the Streptomyces malachitofuscus ctf9. Braz J Microbiol 42:592–604. CrossRefGoogle Scholar
  97. Sharma A, Sharma US (1997) Liposomes in drug delivery: progress and limitations. Int J Pharm 154:123–140. CrossRefGoogle Scholar
  98. Shukla A, Singh B, Katare OP (2011) Significant systemic and mucosal immune response induced on oral delivery of diphtheria toxoid using nano-bilosomes. Br J Pharmacol 164:820–827. CrossRefGoogle Scholar
  99. Steen E, Terry BM, J Rivera E, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR, de la Monte SM (2005) Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease–is this type 3 diabetes? J Alzheimer’s Disease 7(1):63–80. CrossRefGoogle Scholar
  100. Tarkka MT, Sarniguet A, Frey-Klett P (2009) Inter-kingdom encounters: recent advances in molecular bacterium–fungus interactions. Curr Genet 55:233–243. CrossRefGoogle Scholar
  101. Tawiah AA, Gbedema SY, Adu F, Boamah VE, Annan K (2012) Antibiotic producing microorganisms from River Wiwi, Lake Bosomtwe and the Gulf of Guinea at Doakor Sea Beach, Ghana. BMC Microbiol 12:234. CrossRefGoogle Scholar
  102. The world is running out of antibiotics, WHO report confirms. News release, 20 September 2017Google Scholar
  103. Thursby E, Juge N (2017) Introduction to the human gut microbiota. Biochem J 474:1823–1836. CrossRefGoogle Scholar
  104. Tiwari P, Nathiya R, Mahalingam G (2017) Antidiabetic activity of endophytic fungi isolated from Ficusreligiosa. Asian J Pharm Clin Res 10:59–61. CrossRefGoogle Scholar
  105. Tuan-Mahmood TM, McCrudden MT, Torrisi BM, McAlister E, Garland MJ, Singh TR, Donnelly RF (2013) Microneedles for intradermal and transdermal drug delivery. Eur J Pharm Sci 50:623–637. CrossRefGoogle Scholar
  106. Vauthier C (2012) Formulating nanoparticles to achieve oral and intravenous delivery of challenging drugs. In: Tiddy G, Tan R (eds) Nano formulation, pp 1–19.
  107. Verstegen MW, Williams BA (2002) Alternatives to the use of antibiotics as growth promoters for monogastric animals. Anim Biotechnol 13:113–127. CrossRefGoogle Scholar
  108. Wang SW, Fan L (1990) Clinical features of multiple organ failure in the elderly. Chin Med J 103:763–767Google Scholar
  109. Watkins R, Wu L, Zhang C, Davis RM, Xu B (2015) Natural product-based nanomedicine: recent advances and issues. Int J Nanomedicine 10:6055. CrossRefGoogle Scholar
  110. Webster NS (2014) Cooperation, communication, and co-evolution: grand challenges in microbial symbiosis research. Front Microbiol 5:164. CrossRefGoogle Scholar
  111. West DB, Iakougova O, Olsson C, Ross D, Ohmen J, Chatterjee A (2000) Mouse genetics/genomics: an effective approach for drug target discovery and validation. Med Res Rev 20:216–230.<216::AID-MED6>3.0.CO;2-0 CrossRefGoogle Scholar
  112. World Health Organization (2016) Global report on diabetes. World Health Organization, Geneva Google Scholar
  113. Yellepeddi VK, Donnelly RF, Singh TRR (2015) Nanotechnology-based applications for transdermal delivery of therapeutics. In: Donnelly RF, Singh TRR (eds) Novel delivery systems for transdermal and intradermal drug delivery. Wiley, Hoboken, pp 125–146CrossRefGoogle Scholar
  114. Zhang L (2005) Integrated approaches for discovering novel drugs from microbial natural products. In: Zhang L, Demain AL (eds) Natural products: drug discovery and therapeutic medicine. Humana Press, Totowa, pp 33–55. CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Debashish Mohanta
    • 1
  • S. Maneesha
    • 1
  • Rajesh Ghangal
    • 1
  • Manu Solanki
    • 1
  • Soma Patnaik
    • 1
    Email author
  1. 1.Department of Biotechnology, Faculty of Engineering and TechnologyManav Rachna International Institute of Research and Studies (Deemed to be University) (Formerly Manav Rachna International University)FaridabadIndia

Personalised recommendations