Endophytes as sources of antibiotics

Biochemical Pharmacology

Volumn 134, Issue , 2017, Pages 1-17

  Martinez Klimova, Elena ^a   Rodríguez Peña, Karol ^a   Sánchez, Sergio ^a  

^a UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO   (Mexico)

Author keywords

Antibacterial; Antifungal; Antimalarial; Endophytes; Natural products

Indexed keywords

ANTIBIOTIC AGENT; NATURAL PRODUCT; ORGANIC COMPOUND; PEPTIDE DERIVATIVE; ANTIINFECTIVE AGENT; BIOLOGICAL PRODUCT;

ANTIBACTERIAL ACTIVITY; DRUG IDENTIFICATION; ENDOPHYTE; GEOGRAPHIC DISTRIBUTION; MICROBIOLOGICAL EXAMINATION; NONHUMAN; NUCLEOTIDE SEQUENCE; PLANT TAXONOMY; PRIORITY JOURNAL; REVIEW; TAXONOMY; BACTERIAL PHENOMENA AND FUNCTIONS; BACTERIUM; CHEMISTRY; DRUG EFFECTS; GROWTH, DEVELOPMENT AND AGING; HUMAN; ISOLATION AND PURIFICATION; PLANT;

ANTI-BACTERIAL AGENTS; BACTERIA; BACTERIAL PHYSIOLOGICAL PHENOMENA; BIOLOGICAL PRODUCTS; ENDOPHYTES; HUMANS; PLANTS;

EID: 85006721645     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2016.10.010     Document Type: Review

References (78)

1. [1] Sanchez, S., Demain, A.L., Valuable products from microbes. Neelam, G., Abhinav, A., (eds.) Microbes in Process, 2014, Nova Scientific Publishers Inc, USA, 23–57 ISBN: 978-1-63117-127-7.
2. [2] Alvin, A., Miller, K.I., Neilan, B.A., Exploring the potential of endophytes from medicinal plants as sources of antimycobacterial compounds. Microbiol. Res. 169:7–8 (2014), 483–495, 10.1016/j.micres.2013.12.009.
3. [3] Buatong, J., Phongpaichit, S., Rukachaisirikul, V., Sakayaroj, J., Antimicrobial activity of crude extracts from mangrove fungal endophytes. World J. Microbiol. Biotechnol. 27:12 (2011), 3005–3008, 10.1007/s11274-011-0765-8.
4. [4] Janso, J.E., Carter, G.T., Biosynthetic potential of phylogenetically unique endophytic actinomycetes from tropical plants. Appl. Environ. Microbiol. 76:13 (2010), 4377–4386, 10.1128/AEM.02959-09.
5. [5] Aly, A.H., Debbab, A., Proksch, P., Fungal endophytes: unique plant inhabitants with great promises. Appl. Microbiol. Biotechnol. 90:6 (2011), 1829–1845, 10.1007/s00253-011-3270-y.
6. [6] Larran, S., Simón, M.R., Moreno, M.V., Siurana, M.P.S., Perelló, A., Endophytes from wheat as biocontrol agents against tan spot disease. Biol. Control 92 (2016), 17–23, 10.1016/j.biocontrol.2015.09.002.
7. [7] Wilson, D., Endophyte: the evolution of a term, and clarification of its use and definition. Oikos 10:2307/3545919 (1995), 274–276, 10.2307/3545919.
8. [8] Mani, V.M., Soundari, A.P., Karthiyaini, D., Preeth, K., Bioprospecting endophytic fungi and their metabolites from medicinal tree Aegle marmelos in Western Ghats, India. Mycobiology 43:3 (2015), 303–310, 10.5941/MYCO.2015.43.3.303.
9. [9] Zhang, H.W., Song, Y.C., Tan, R.X., Biology and chemistry of endophytes. Natural Prod. Rep. 23:5 (2006), 753–771, 10.1039/B609472B.
10. [10] Golinska, P., Wypij, M., Agarkar, G., Rathod, D., Dahm, H., Rai, M., Endophytic actinobacteria of medicinal plants: diversity and bioactivity. Anton Van Leeuwenhoek 108:2 (2015), 267–289.
11. [11] Santoyo, G., Moreno-Hagelsieb, G., Del Carmen Orozco-Mosqueda, M., Glick, B.R., Plant growth-promoting bacterial endophytes. Microbiol. Res. 183 (2016), 92–99, 10.1016/j.micres.2015.11.008.
12. [12] Hardoim, P.R., van Overbeek, L.S., Elsas, J.D., Properties of bacterial endophytes and their proposed role in plant growth. Trends Microbiol. 16:10 (2008), 463–471, 10.1016/j.tim.2008.07.008.
13. [13] Madhurama, G., Sonam, D., Urmil, P.G., Ravindra, N.K., Diversity and biopotential of endophytic actinomycetes from three medicinal plants in India. African J. Microbiol. Res. 8:2 (2014), 184–191, 10.5897/ajmr2012.2452.
14. [14] Hyde, K., Soytong, K., The fungal endophyte dilemma. Fungal Divers, 33(163173), 2008, 2.
15. [15] Abdalla, M.A., Matasyoh, J.C., Endophytes as producers of peptides: an overview about the recently discovered peptides from endophytic microbes. Nat. Prod. Bioprospect. 4:5 (2014), 257–270, 10.1007/s13659-014-0038-y.
16. [16] Kusari, P., Kusari, S., Spiteller, M., Kayser, O., Implications of endophyte-plant crosstalk in light of quorum responses for plant biotechnology. Appl. Microbiol. Biotechnol. 99:13 (2015), 5383–5390, 10.1007/s00253-015-6660-8.
17. [17] Deepika, V.B., Murali, T.S., Satyamoorthy, K., Modulation of genetic clusters for synthesis of bioactive molecules in fungal endophytes: A review. Microbiol. Res. 182 (2016), 125–140, 10.1016/j.micres.2015.10.009.
18. [18] Gardner, J.M., Feldman, A.W., Zablotowicz, R.M., Identity and behavior of xylem-residing bacteria in rough lemon roots of Florida citrus trees. Appl. Environ. Microbiol. 43:6 (1982), 1335–1342.
19. [19] Verma, V.C., Gond, S.K., Kumar, A., Mishra, A., Kharwar, R.N., Gange, A.C., Endophytic actinomycetes from Azadirachta indica A. Juss.: isolation, diversity, and anti-microbial activity. Microb. Ecol. 57:4 (2009), 749–756, 10.1007/s00248-008-9450-3.
20. [20] Coombs, J.T., Franco, C.M., Isolation and identification of actinobacteria from surface-sterilized wheat roots. Appl. Environ. Microbiol. 69:9 (2003), 5603–5608.
21. [21] Cao, L., Qiu, Z., Dai, X., Tan, H., Lin, Y., Zhou, S., Isolation of endophytic actinomycetes from roots and leaves of banana (Musa acuminata) plants and their activities against Fusarium oxysporum f. sp. cubense. World J. Microbiol. Biotechnol. 20:5 (2004), 501–504.
22. [22] Cao, L., Qiu, Z., You, J., Tan, H., Zhou, S., Isolation and characterization of endophytic Streptomyces strains from surface-sterilized tomato (Lycopersicon esculentum) roots. Lett. Appl. Microbiol. 39:5 (2004), 425–430.
23. [23] Izumi, H., Anderson, I.C., Alexander, I.J., Killham, K., Moore, E.R., Endobacteria in some ectomycorrhiza of Scots pine (Pinus sylvestris). FEMS Microbiol. Ecol. 56:1 (2006), 34–43.
24. [24] Gohain, A., Gogoi, A., Debnath, R., Yadav, A., Singh, B.P., Gupta, V.K., et al. Antimicrobial biosynthetic potential and genetic diversity of endophytic actinomycetes associated with medicinal plants. FEMS Microbiol. Lett., 362(19), 2015, fnv158.
25. [25] Qin, S., Wang, H.-B., Chen, H.-H., Zhang, Y.-Q., Jiang, C.-L., Xu, L.-H., et al. Glycomyces endophyticus sp. nov., an endophytic actinomycete isolated from the root of Carex baccans Nees. Int. J. Syst. Evol. Microbiol. 58:11 (2008), 2525–2528.
26. [26] Melo, I.S., Santos, S.N., Rosa, L.H., Parma, M.M., Silva, L.J., Queiroz, S.C., et al. Isolation and biological activities of an endophytic Mortierella alpina strain from the Antarctic moss Schistidium antarctici. Extremophiles 18:1 (2014), 15–23, 10.1007/s00792-013-0588-7.
27. [27] Miller, K.I., Qing, C., Sze, D.M., Neilan, B.A., Investigation of the biosynthetic potential of endophytes in traditional Chinese anticancer herbs. PLoS ONE, 7(5), 2012, e35953, 10.1371/journal.pone.0035953.
28. [28] Miller, K.I., Qing, C., Sze, D.M., Roufogalis, B.D., Neilan, B.A., Culturable endophytes of medicinal plants and the genetic basis for their bioactivity. Microb. Ecol. 64:2 (2012), 431–449, 10.1007/s00248-012-0044-8.
29. [29] Guimarães, D.O., Borges, W.S., Kawano, C.Y., Ribeiro, P.H., Goldman, G.H., Nomizo, A., et al. Biological activities from extracts of endophytic fungi isolated from Viguiera arenaria and Tithonia diversifolia. FEMS Immunol. Med. Microbiol. 52:1 (2008), 134–144, 10.1111/j.1574-695X.2007.00354.x.
30. [30] Arivudainambi, U.S., Anand, T.D., Shanmugaiah, V., Karunakaran, C., Rajendran, A., Novel bioactive metabolites producing endophytic fungus Colletotrichum gloeosporioides against multidrug-resistant Staphylococcus aureus. FEMS Immunol. Med. Microbiol. 61:3 (2011), 340–345, 10.1111/j.1574-695X.2011.00780.x.
31. [31] Cui, J.L., Guo, S.X., Xiao, P.G., Antitumor and antimicrobial activities of endophytic fungi from medicinal parts of Aquilaria sinensis. J. Zhejiang Univ. Sci. B 12:5 (2011), 385–392, 10.1631/jzus.B1000330.
32. [32] Ding, X., Liu, K., Deng, B., Chen, W., Li, W., Liu, F., Isolation and characterization of endophytic fungi from Camptotheca acuminata. World J. Microbiol. Biotechnol. 29:10 (2013), 1831–1838, 10.1007/s11274-013-1345-x.
33. [33] Machavariani, N.G., Ivankova, T.D., Sineva, O.N., Terekhova, L.P., Isolation of endophytic actinomycetes from medicinal plants of the Moscow region, Russia. World Appl. Sci. J. 30:11 (2014), 1599–1604.
34. [34] Akinsanya, M.A., Goh, J.K., Lim, S.P., Ting, A.S., Diversity, antimicrobial and antioxidant activities of culturable bacterial endophyte communities in Aloe vera. FEMS Microbiol. Lett., 362(23), 2015, fnv184, 10.1093/femsle/fnv184.
35. [35] Bezerra, J.D., Nascimento, C.C., Barbosa, Rdo N., da Silva, D.C., Svedese, V.M., Silva-Nogueira, E.B., et al. Endophytic fungi from medicinal plant Bauhinia forficata: diversity and biotechnological potential. Braz. J. Microbiol. 46:1 (2015), 49–57, 10.1590/S1517-838246120130657.
36. [36] Chowdhary, K., Kaushik, N., Fungal endophyte diversity and bioactivity in the indian medicinal plant Ocimum sanctum Linn. PLoS ONE, 10(11), 2015, e0141444, 10.1371/journal.pone.0141444.
37. [37] Mousa, W.K., Schwan, A., Davidson, J., Strange, P., Liu, H., Zhou, T., et al. An endophytic fungus isolated from finger millet (Eleusine coracana) produces anti-fungal natural products. Front Microbiol, 6, 2015, 1157, 10.3389/fmicb.2015.01157.
38. [38] Alvin, A., Kalaitzis, J.A., Sasia, B., Neilan, B.A., Combined genetic and bioactivity-based prioritization leads to the isolation of an endophyte-derived antimycobacterial. J. Appl. Microbiol., 2016, 10.1111/jam.13062. 10.1111/jam.13062.
39. [39] Tonial, F., Maia, B.H., Gomes-Figueiredo, J.A., Sobottka, A.M., Bertol, C.D., Nepel, A., et al. Influence of culturing conditions on bioprospecting and the antimicrobial potential of endophytic fungi from Schinus terebinthifolius. Curr. Microbiol. 72:2 (2016), 173–183, 10.1007/s00284-015-0929-0.
40. [40] Tanvir, R., Sajid, I., Hasnain, S., Kulik, A., Grond, S., Rare actinomycetes Nocardia caishijiensis and Pseudonocardia carboxydivorans as endophytes, their bioactivity and metabolites evaluation. Microbiol. Res. 185 (2016), 22–35, 10.1016/j.micres.2016.01.003.
41. [41] Wang, L., Qiu, P., Long, X.-F., Zhang, S., Zeng, Z.-G., Tian, Y.-Q., Comparative analysis of chemical constituents, antimicrobial and antioxidant activities of ethylacetate extracts of Polygonum cuspidatum and its endophytic actinomycete, Streptomyces sp. A0916. Chinese. J. Nat. Med. 14:2 (2016), 117–123, 10.1016/s1875-5364(16)60004-3.
42. [42] Castillo, U.F., Strobel, G.A., Ford, E.J., Hess, W.M., Porter, H., Jensen, J.B., et al. Munumbicins, wide-spectrum antibiotics produced by Streptomyces NRRL 30562, endophytic on Kennedia nigriscans. Microbiology 148:9 (2002), 2675–2685.
43. [43] Castillo, U.F., Strobel, G.A., Mullenberg, K., Condron, M.M., Teplow, D.B., Folgiano, V., et al. Munumbicins E-4 and E-5: novel broad-spectrum antibiotics from Streptomyces NRRL 3052. FEMS Microbiol. Lett. 255:2 (2006), 296–300, 10.1111/j.1574-6968.2005.00080.x.
44. [44] Castillo, U., Harper, J.K., Strobel, G.A., Sears, J., Alesi, K., Ford, E., et al. Kakadumycins, novel antibiotics from Streptomyces sp. NRRL 30566, an endophyte of Grevillea pteridifolia. FEMS Microbiol. Lett. 224:2 (2003), 183–190, 10.1016/s0378-1097(03)00426-9.
45. [45] Ezra, D., Castillo, U.F., Strobel, G.A., Hess, W.M., Porter, H., Jensen, J.B., et al. Coronamycins, peptide antibiotics produced by a verticillate Streptomyces sp. (MSU-2110) endophytic on Monstera sp. Microbiology 150:Pt 4 (2004), 785–793, 10.1099/mic.0.26645-0.
46. [46] Seto, Y., Takahashi, K., Matsuura, H., Kogami, Y., Yada, H., Yoshihara, T., et al. Novel cyclic peptide, epichlicin, from the endophytic fungus, Epichloe typhina. Biosci. Biotechnol. Biochem. 71:6 (2007), 1470–1475, 10.1271/bbb.60700.
47. [47] National Center for Biotechnology Information U.S.N.L.o.M. Taxonomy 8600 Rockville Pike, Bethesda MD, 20894 USA (Available from: < http://www.ncbi.nlm.nih.gov/taxonomy>).
48. [48] Ren, Y., Strobel, G.A., Graff, J.C., Jutila, M., Park, S.G., Gosh, S., et al. Colutellin A, an immunosuppressive peptide from Colletotrichum dematium. Microbiology 154:Pt 7 (2008), 1973–1979, 10.1099/mic.0.2008/017954-0.
49. [49] Chomcheon, P., Wiyakrutta, S., Aree, T., Sriubolmas, N., Ngamrojanavanich, N., Mahidol, C., et al. Curvularides A-E: antifungal hybrid peptide-polyketides from the endophytic fungus Curvularia geniculata. Chemistry 16:36 (2010), 11178–11185, 10.1002/chem.201000652.
50. [50] Tejesvi, M.V., Segura, D.R., Schnorr, K.M., Sandvang, D., Mattila, S., Olsen, P.B., et al. An antimicrobial peptide from endophytic Fusarium tricinctum of Rhododendron tomentosum Harmaja. Fungal Divers 60:1 (2013), 153–159, 10.1007/s13225-013-0227-8.
51. [51] Taechowisan, T., Lu, C., Shen, Y., Lumyong, S., Secondary metabolites from endophytic Streptomyces aureofaciens CMUAc130 and their antifungal activity. Microbiology 151:Pt 5 (2005), 1691–1695, 10.1099/mic.0.27758-0.
52. [52] Chomcheon, P., Wiyakrutta, S., Sriubolmas, N., Ngamrojanavanich, N., Isarangkul, D., Kittakoop, P., 3-Nitropropionic acid (3-NPA), a potent antimycobacterial agent from endophytic fungi: is 3-NPA in some plants produced by endophytes?. J. Nat. Prod. 68:7 (2005), 1103–1105.
53. [53] Ganihigama, D.U., Sureram, S., Sangher, S., Hongmanee, P., Aree, T., Mahidol, C., et al. Antimycobacterial activity of natural products and synthetic agents: pyrrolodiquinolines and vermelhotin as anti-tubercular leads against clinical multidrug resistant isolates of Mycobacterium tuberculosis. Eur. J. Med. Chem. 89 (2015), 1–12, 10.1016/j.ejmech.2014.10.026.
54. [54] Martínez-Luis, S., Della-Togna, G., Coley, P.D., Kursar, T.A., Gerwick, W.H., Cubilla-Rios, L., Antileishmanial constituents of the Panamanian endophytic fungus Edenia sp. J. Nat. Prod. 71:12 (2008), 2011–2014.
55. [55] Rukachaisirikul, V., Sommart, U., Phongpaichit, S., Sakayaroj, J., Kirtikara, K., Metabolites from the endophytic fungus Phomopsis sp. PSU-D15. Phytochemistry 69:3 (2008), 783–787, 10.1016/j.phytochem.2007.09.006.
56. [56] Aly, A.H., Edrada-Ebel, R., Wray, V., Muller, W.E., Kozytska, S., Hentschel, U., et al. Bioactive metabolites from the endophytic fungus Ampelomyces sp. isolated from the medicinal plant Urospermum picroides. Phytochemistry 69:8 (2008), 1716–1725, 10.1016/j.phytochem.2008.02.013.
57. [57] Li, E., Tian, R., Liu, S., Chen, X., Guo, L., Che, Y., Pestalotheols A− D, bioactive metabolites from the plant endophytic fungus Pestalotiopsis theae. J. Nat. Prod. 71:4 (2008), 664–668.
58. [58] Hoffman, A.M., Mayer, S.G., Strobel, G.A., Hess, W.M., Sovocool, G.W., Grange, A.H., et al. Purification, identification and activity of phomodione, a furandione from an endophytic Phoma species. Phytochemistry 69:4 (2008), 1049–1056, 10.1016/j.phytochem.2007.10.031.
59. [59] Gu, W., Bioactive metabolites from Alternaria brassicicola ML-P08, an endophytic fungus residing in Malus halliana. World J. Microbiol. Biotechnol. 25:9 (2009), 1677–1683, 10.1007/s11274-009-0062-y.
60. [60] Lim, C., Kim, J., Choi, J.N., Ponnusamy, K., Jeon, Y., Kim, S.-U., et al. Identification, fermentation, and bioactivity against Xanthomonas oryzae of antimicrobial metabolites isolated from Phomopsis longicolla S1B4. J. Microbiol. Biotechnol. 20:3 (2010), 494–500.
61. [61] Ding, L., Maier, A., Fiebig, H.H., Lin, W.H., Hertweck, C., A family of multicyclic indolosesquiterpenes from a bacterial endophyte. Org. Biomol. Chem. 9:11 (2011), 4029–4031, 10.1039/c1ob05283g.
62. [62] Sun, Z.L., Zhang, M., Zhang, J.F., Feng, J., Antifungal and cytotoxic activities of the secondary metabolites from endophytic fungus Massrison sp. Phytomedicine 18:10 (2011), 859–862, 10.1016/j.phymed.2011.01.019.
63. [63] Sonaimuthu, V., Parihar, S., Prakash, Thakur J., Luqman, S., Saikia, D., Chinotiya, C.S., et al. Tenuazonic acid: a promising antitubercular principle from Alternaria alternate. Microbiol. Res., 2(2), 2011, 17, 10.4081/mr.2011.e17.
64. [64] Inahashi, Y., Iwatsuki, M., Ishiyama, A., Namatame, M., Nishihara-Tsukashima, A., Matsumoto, A., et al. Spoxazomicins A-C, novel antitrypanosomal alkaloids produced by an endophytic actinomycete, Streptosporangium oxazolinicum K07–0460(T). J. Antibiot. (Tokyo) 64:4 (2011), 303–307, 10.1038/ja.2011.16.
65. [65] Inahashi, Y., Matsumoto, A., Omura, S., Takahashi, Y., Streptosporangium oxazolinicum sp. nov., a novel endophytic actinomycete producing new antitrypanosomal antibiotics, spoxazomicins. J. Antibiot. (Tokyo) 64:4 (2011), 297–302, 10.1038/ja.2011.18.
66. [66] Johann, S., Rosa, L.H., Rosa, C.A., Perez, P., Cisalpino, P.S., Zani, C.L., et al. Antifungal activity of altenusin isolated from the endophytic fungus Alternaria sp. against the pathogenic fungus Paracoccidioides brasiliensis. Rev. Iberoam. Micol. 29:4 (2012), 205–209, 10.1016/j.riam.2012.02.002.
67. [67] Wijeratne, E.M., He, H., Franzblau, S.G., Hoffman, A.M., Gunatilaka, A.A., Phomapyrrolidones A-C, antitubercular alkaloids from the endophytic fungus Phoma sp. NRRL 46751. J. Nat. Prod. 76:10 (2013), 1860–1865, 10.1021/np400391p.
68. [68] Forcina, G.C., Castro, A., Bokesch, H.R., Spakowicz, D.J., Legaspi, M.E., Kucera, K., et al. Stelliosphaerols A and B, sesquiterpene-polyol conjugates from an Ecuadorian fungal endophyte. J. Nat. Prod. 78:12 (2015), 3005–3010, 10.1021/acs.jnatprod.5b00749.
69. [69] Frederickson, M.E., Gordon, D.M., The devil to pay: a cost of mutualism with Myrmelachista schumanni ants in 'devil's gardens’ is increased herbivory on Duroia hirsuta trees. Proc. Biol. Sci. 274:1613 (2007), 1117–1123, 10.1098/rspb.2006.0415.
70. [70] Zhang, J., Liu, D., Wang, H., Liu, T., Xin, Z., Fusartricin, a sesquiterpenoid ether produced by an endophytic fungus Fusarium tricinctum Salicorn 19. Eur. Food Res. Technol. 240:4 (2015), 805–814, 10.1007/s00217-014-2386-6.
71. [71] Shiono, Y., Koyama, H., Murayama, T., Koseki, T., New sesquiterpenes from the endophyte Microdiplodia sp TT-12 and their antimicrobial activity. Phytochem. Lett. 14 (2015), 143–147, 10.1016/j.phytol.2015.10.004.
72. [72] Liu, K., Yang, Y., Miao, C.P., Zheng, Y.K., Chen, J.L., Chen, Y.W., et al. Koningiopisins A-H, polyketides with synergistic antifungal activities from the endophytic fungus Trichoderma koningiopsis. Planta Med., 2015, 10.1055/s-0035-1558228. 10.1055/s-0035-1558228.
73. [73] Ibrahim, S.R.M., Elkhayat, E.S., Mohamed, G.A., Khedr, A.I.M., Fouad, M.A., Kotb, M.H.R., et al. Aspernolides F and G, new butyrolactones from the endophytic fungus Aspergillus terreus. Phytochem. Lett. 14 (2015), 84–90, 10.1016/j.phytol.2015.09.006.
74. [74] Supong, K., Thawai, C., Choowong, W., Kittiwongwattana, C., Thanaboripat, D., Laosinwattana, C., et al. Antimicrobial compounds from endophytic Streptomyces sp. BCC72023 isolated from rice (Oryza sativa L.). Res. Microbiol., 2016, 10.1016/j.resmic.2016.01.004. 10.1016/j.resmic.2016.01.004.
75. [75] Jouda, J.B., Mawabo, I.K., Notedji, A., Mbazoa, C.D., Nkenfou, J., Wandji, J., et al. Anti-mycobacterial activity of polyketides from Penicillium sp. endophyte isolated from Garcinia nobilis against Mycobacterium smegmatis. Int. J. Mycobacteriol., 2016, 10.1016/j.ijmyco.2016.02.007.
76. [76] Google. “Google Maps”, 2016 (Available from: < https://www.google.com.mx/maps/>).
77. [77] Roberts, J.P., Incentives aim to boost antibiotic development. Nat. Biotechnol., 30(8), 2012, 735.
78. [78] Scott, A., Europe to boost drug discovery. Chem. Eng. News, 91(7), 2013, 8.