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Does the Future of Antibiotics Lie in Secondary Metabolites Produced by Xenorhabdus spp.? A Review

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Abstract

The over-prescription of antibiotics for treatment of infections is primarily to blame for the increase in bacterial resistance. Added to the problem is the slow rate at which novel antibiotics are discovered and the many processes that need to be followed to classify antimicrobials safe for medical use. Xenorhabdus spp. of the family Enterobacteriaceae, mutualistically associated with entomopathogenic nematodes of the genus Steinernema, produce a variety of antibacterial peptides, including bacteriocins, depsipeptides, xenocoumacins and PAX (peptide antimicrobial-Xenorhabdus) peptides, plus additional secondary metabolites with antibacterial and antifungal activity. The secondary metabolites of some strains are active against protozoa and a few have anti-carcinogenic properties. It is thus not surprising that nematodes invaded by a single strain of a Xenorhabdus species are not infected by other microorganisms. In this review, the antimicrobial compounds produced by Xenorhabdus spp. are listed and the gene clusters involved in synthesis of these secondary metabolites are discussed. We also review growth conditions required for increased production of antimicrobial compounds.

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References

  1. Stubbendieck RM, Straight PD (2016) Multifaceted interfaces of bacterial competition. J Bacteriol 198:2145–2155

    CAS  Google Scholar 

  2. Hibbing ME, Fuqua C, Parsek MR, Peterson BS (2010) Bacterial competition: surviving and thriving in the microbial jungle. Nat Rev Micro 8:15–25

    CAS  Google Scholar 

  3. Kim W, Racimo F, Schluter J, Levy SB, Foster KR (2014) Importance of positioning for microbial evolution. Proc Natl Acad Sci U S A 111:E1639–E1647

    CAS  Google Scholar 

  4. Asally M, Kittisopikul M, Rué P, Du Y, Hu Z, Çağatay T, Robison AB, Lu H, Garcia-Ojalvo J, Süel GM (2012) Localized cell death focuses mechanical forces during 3D patterning in a biofilm. Proc Natl Acad Sci U S A 109:18891–18896

    CAS  Google Scholar 

  5. Kreth J, Zhang Y, Herzberg MC (2008) Streptococcal antagonism in oral biofilms: Streptococcus sanguinis and Streptococcus gordonii interference with Streptococcus mutans. J Bacteriol 2008 190: 4632–4640

  6. Zheng X, Zhang K, Zhou X, Liu C, Li M, Li Y, Wang R, Li Y, Li J, Shi W, Xu X (2013) Involvement of gshAB in the interspecies competition within oral biofilm. J Dent Res 92:819–824

    CAS  Google Scholar 

  7. Chen J, Lee SM, Mao Y (2004) Protective effect of exopolysaccharide colanic acid of Escherichia coli O157:H7 to osmotic and oxidative stress. Int J Food Microbiol 93:281–286

    CAS  Google Scholar 

  8. Prokopenko MG, Hirst MB, De Brabandere L, Lawrence DJP, Berelson WM, Granger J, Chang BX, Dawson S, Crane EJ, Chong L, Thamdrup B, Townsend-Small A, Sigman DM (2013) Nitrogen losses in anoxic marine sediments driven by Thioploca-anammox bacterial consortia. Nature 500:194–198

    CAS  Google Scholar 

  9. Koskiniemi S, Sun S, Berg OG, Andersson DI (2012) Selection-driven gene loss in bacteria. PLoS Genet 8:1–8

    Google Scholar 

  10. Morris JJ (2015) Black Queen evolution: the role of leakiness in structuring microbial communities. Trends Genet 31:475–482

    CAS  Google Scholar 

  11. Johnson DR, Goldschmidt F, Lilja EE, Achermann (2012) Metabolic specialization and the assembly of microbial communities. ISME J 6:1985–1991

    CAS  Google Scholar 

  12. Kaufman G (2011) Antibiotics: mode of action and mechanisms of resistance. Nurs Stand 24:49–55

    Google Scholar 

  13. Lambert PA (2005) Bacterial resistance to antibiotics: modified target sites. Adv Drug Deliv Rev 57:1471–1485

    CAS  Google Scholar 

  14. Peterson E, Kaur P (2018) Antibiotic resistance mechanisms in bacteria: relationships between resistance determinants of antibiotic producers, environmental bacteria, and clinical pathogens. Front Microbiol 9 http://www.ncbi.nlm.nih.gov/pubmed/27227291

  15. Munita JM, Arias CA (2016) Mechanisms of antibiotic resistance. Microbiol Spectr 4 http://www.ncbi.nlm.nih.gov/pubmed/27227291

  16. Jacoby GA (2009) AmpC Β-Lactamases. Clin Microbiol Rev 22:161–182

    CAS  Google Scholar 

  17. Abraham E, Chain E (1940) An enzyme from bacteria able to destroy penicillin. Nature 146:677–678

    Google Scholar 

  18. Hancock REW, Brinkman FSL (2002) Function of Pseudomonas porins in uptake and efflux. Annu Rev Microbiol 56:17–38

    CAS  Google Scholar 

  19. Quinn JP, Dudek EJ, Divincenzo CA, Lucks DA, Lerner SA (1986) Emergence of resistance to imipenem during therapy for Pseudomonas aeruginosa infections. J Infect Dis 154:289–294

    CAS  Google Scholar 

  20. Poole K (2005) Efflux-mediated antimicrobial resistance. J Antimicrob Chemother 56:20–51

    CAS  Google Scholar 

  21. Nikaido H (2003) Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 67:593–656

    CAS  Google Scholar 

  22. Enright MC, Robinson AD, Randle G, Feil EJ, Grundmann H, Spratt BG (2002) The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc Natl Acad Sci U S A 99:7687–7692

    CAS  Google Scholar 

  23. Grebe T, Hakenbeck R (1996) Penicillin-binding proteins 2b and 2x of Streptococcus pneumoniae are primary resistance determinants for different classes of β-lactam antibiotics. Antimicrob Agents Chemother 40:829–834

    CAS  Google Scholar 

  24. Ropp PA, Hu M, Olesky M, Nicholas RA (2002) Mutations in ponA, the gene encoding penicillin-binding protein 1, and a novel locus, penC, are required for high-level chromosomally mediated penicillin resistance in Neisseria gonorrhoeae. Antimicrob Agents Chemother 46:769–777

    CAS  Google Scholar 

  25. Neu HC (1992) The crisis in antibiotic resistance. Science 257:1064–1073

    CAS  Google Scholar 

  26. Colavecchio A, Cadieux B, Lo A, Goodridge LD (2017) Bacteriophages contribute to the spread of antibiotic resistance genes among foodborne pathogens of the Enterobacteriaceae family - a review. Front Microbiol 8:1–13

    Google Scholar 

  27. Dunphy GB, Webster JM (1991) Antihemocytic surface components of Xenorhabdus nematophilus var. dutki and their modification by serum nonimmune larvae of Galleria mellonella. J Invertebr Pathol 58:40–51

    Google Scholar 

  28. Yang J, Zeng H-M, Lin H-F, Yang X-F, Liu Z, Guo L-H, Yuan J-J, Qiu D-W (2012) An insecticidal protein from Xenorhabdus budapestensis that results in prophenoloxidase activation in the wax moth, Galleria mellonella. J Invertebr Pathol 110:60–67

    CAS  Google Scholar 

  29. Dreyer J, Malan AP, Dicks LMT (2018) Bacteria of the genus Xenorhabdus, a novel source of bioactive compounds. Front Microbiol 9:1–14

    Google Scholar 

  30. Zhou Q, Grundmann F, Kaiser M, Schiell M, Gaudriault S, Batzer A, Kurz M, Bode HB (2013) Structure and biosynthesis of xenoamicins from entomopathogenic Xenorhabdus. Chem Eur J 19:16772–16779

    CAS  Google Scholar 

  31. Kronenwerth M, Bozhüyük KAJ, Kahnt AS, Steinhilber D, Gaudriault S, Kaiser M, Bode HB (2014) Characterisation of taxlllaids A-G; natural products from Xenorhabdus indica. Chem - A Eur J 20:17478–17487

    CAS  Google Scholar 

  32. Crawford JM, Portmann C, Kontnik R, Walsh CT, Clardy J (2011) NRPS substrate promiscuity diversifies the xenematides. Org Lett 13:5144–5147

    CAS  Google Scholar 

  33. Grundmann F, Kaiser M, Kurz M, Schiell M, Batzer A, Bode HB (2013) Structure determination of the bioactive depsipeptide xenobactin from Xenorhabdus sp. PB30.3. RSC Adv 3:22072–22077

    CAS  Google Scholar 

  34. Ohlendorf B, Simon S, Wiese J, Imhoff JF (2011) Szentiamide, an N-formylated cyclic depsipeptide from Xenorhabdus szentirmaii DSM 16338 T. Nat Prod Commun 6:1247–1250

    CAS  Google Scholar 

  35. Nollmann FI, Dowling A, Kaiser M, Deckmann K, Grösch S, French-Constant R, Bode H (2012) Synthesis of szentiamide, a depsipeptide from entomopathogenic Xenorhabdus szentirmaii with activity against Plasmodium falciparum. Beilstein J Org Chem 8:528–533

    CAS  Google Scholar 

  36. Reimer D, Nollmann FI, Schultz K, Kaiser M, Bode HB (2014) Xenortide biosynthesis by entomopathogenic Xenorhabdus nematophila. J Nat Prod 77:1976–1980

    CAS  Google Scholar 

  37. Esmati N, Maddirala AR, Hussein N, Amawi H, Tiwari AK, Andreana PR (2018) Efficient syntheses and anti-cancer activity of xenortides A-D including ent/epi-stereoisomers. Org Biomol Chem 16:5332–5342

    CAS  Google Scholar 

  38. Hacker C, Cai X, Kegler C, Zhao L, Weickmann K, Wurm JP, Bode HB, Wöhnert J (2018) Structure-based redesign of docking domain interactions modulates the product spectrum of a rhabdopeptide-synthesizing NRPS. Nat Commun 9:4366–4377

    Google Scholar 

  39. Zhao L, Kaiser M, Bode HB (2018) Rhabdopeptide/xenortide-like peptides from Xenorhabdus innexi with terminal amines showing potent antiprotozoal activity. Org Lett 20:5116–5120

    CAS  Google Scholar 

  40. Fuchs SW, Sachs CC, Kegler C, Nollmann FI, Karas M, Bode HB (2012) Neutral loss fragmentation pattern based screening for arginine-rich natural products in Xenorhabdus and Photorhabdus. Anal Chem 84:6948–9655

    CAS  Google Scholar 

  41. Fuchs SW, Proschak A, Jaskolla TW, Karas M, Bode HB (2011) Structure elucidation and biosynthesis of lysine-rich cyclic peptides in Xenorhabdus namtophila. Org Biomol Chem 9:3130–3132

    CAS  Google Scholar 

  42. Gualtieri M, Aumelas A, Thaler J-O (2009) Identification of a new antimicrobial lysine-rich cyclolipopeptide family from Xenorhabdus nematophila. J Antibiot (Tokyo) 62:295–302

    CAS  Google Scholar 

  43. Cai X, Challinor VL, Zhao L, Reimer D, Adihou H, Grün P, Kaiser M, Bode HB (2017) Biosynthesis of the antibiotic nematophin and its elongated derivatives in entomopathogenic bacteria. Org Lett 19:806–809

    CAS  Google Scholar 

  44. Singh J, Banerjee N (2008) Transcriptional analysis and functional characterization of a gene pair encoding iron-regulated xenocin and immunity proteins of Xenorhabdus nematophila. J Bacteriol 190:3877–3885

    CAS  Google Scholar 

  45. Thaler JO, Baghdiguian S, Boemare N (1995) Purification and characterization of xenorhabdicin, a phage tail-like bacteriocin, from the lysogenic strain F1 of Xenorhabdus nematophilus. Appl Environ Microbiol 61:2049–2052

    CAS  Google Scholar 

  46. Proschak A, Zhou Q, Schöner T, Thanwisai A, Kresovic D, Dowling A, Ffrench-constant R, Proschak E, Bode HB (2014) Biosynthesis of the insecticidal xenocyloins in Xenorhabdus bovienii. ChemBioChem 15:369–372

    CAS  Google Scholar 

  47. Guo S, Zhang S, Fang X, Liu Q, Gao J, Bilal M, Wang Y, Zhang X (2017) Regulation of antimicrobial activity and xenocoumacins biosynthesis by pH in Xenorhabdus nematophila. Microb Cell Factories 16:1–14

    Google Scholar 

  48. Fuchs SW, Grundmann F, Kurz M, Kaiser M, Bode HB (2014) Fabclavines: bioactive peptide – polyketide-polyamino hybrids from Xenorhabdus. Chem Bio Chem 15:512–516

    CAS  Google Scholar 

  49. Brachmann AO, Reimer D, Lorenzen W, Alonso EA, Kopp Y, Piel J, Bode HB (2012) Reciprocal cross talk between fatty acid and antibiotic biosynthesis in a nematode symbiont. Angew Chemie - Int Ed 51:12086–12089

    CAS  Google Scholar 

  50. Qin Z, Huang S, Yu Y, Deng H (2013) Dithiolopyrrolone natural products: isolation, synthesis and biosynthesis. Mar Drugs 11:3970–3997

    CAS  Google Scholar 

  51. Li B, Wever WJ, Walsh CT, Bowers AA (2014) Dithiolopyrrolones: biosynthesis, synthesis and activity of a unique class of disulfide containing antibiotics. Nat Prod Rep 31:905–923

    Google Scholar 

  52. Houard J, Aumelas A, Noël T, Pages S, Givaudan A, Fitton-Ouhabi V, Villain-Guillot P, Gaultieri M (2013) Cabanillasin, a new antifungal metabolite, produced by entomopathogenic Xenorhabdus cabanillasii JM26. J Antibiot 66:617–620

    CAS  Google Scholar 

  53. Masschelein J, Jenner M, Challis GL (2017) Antibiotics from Gram-negative bacteria: a comprehensive overview and selected biosynthetic highlights. Nat Prod Rep 34:712–783

    CAS  Google Scholar 

  54. Crawford JM, Portmann C, Zhang X, Roeffaers MBJ, Clardy J (2012) Small molecule perimeter defense in entomopathogenic bacteria. Proc Natl Acad Sci U S A 109:10821–10826

    CAS  Google Scholar 

  55. Ji D, Yi Y, Kang GH, Choi Y-H, Kim P, Baek N-I, Kim Y (2004) Identification of an antibacterial compound, benzylideneacetone, from Xenorhabdus nematophila against major plant-pathogenic bacteria. FEMS Microbiol Lett 239:241–248

    CAS  Google Scholar 

  56. Xiao Y, Meng F, Qiu D, Yang X (2012) Two novel antimicrobial peptides purified from the symbiotic bacteria Xenorhabdus budapestensis NMC-10. Peptides 35:253–260

    CAS  Google Scholar 

  57. Van Staden ADP, Faure LM, Vermeulen RR, Dicks LMT, Smith C (2019) Functional expression of GFP-fused class I lanthipeptides in Escherichia coli. ACS Synth Biol 8:2220–2227

    Google Scholar 

  58. Belshaw PJ, Walsh CT, Stachelhaus T (1999) Aminoacyl-CoAs as probes of condensation domain selectivity in nonribosomal peptide synthesis. Science 284:486–489

    CAS  Google Scholar 

  59. Marahiel MA, Stachelhaus T, Mootz HD (1997) Modular peptide synthetases involved in nonribosomal peptide synthesis. Chem Rev 97:2651–2674

    CAS  Google Scholar 

  60. Roongsawang N, Siew PL, Washio K, Takano K, Kanaya S, Morikawa M (2005) Phylogenetic analysis of condensation domains in the nonribosomal peptide synthetases. FEMS Microbiol Lett 252:143–151

    CAS  Google Scholar 

  61. Ackerley DF (2016) Cracking the nonribosomal code. Cell Chem Biol 23:535–537

    CAS  Google Scholar 

  62. Inoue M (2011) Total synthesis and functional analysis of non-ribosomal peptides. Chem Rec 11:284–294

    CAS  Google Scholar 

  63. Martínez-Núñez MA, López VEL (2016) Nonribosomal peptides synthetases and their applications in industry. Sustain Chem Process 4:13–20

    Google Scholar 

  64. Finking R, Marahiel MA (2004) Biosynthesis of nonribosomal peptides. Annu Rev Microbiol 58:4530–4488

    Google Scholar 

  65. Steiniger C, Hoffmann S, Süssmuth RD (2019) Desymmetrization of cyclodepsipeptides by assembly mode switching of iterative nonribosomal peptide synthetases. ACS Synth Biol 8:661–667

    CAS  Google Scholar 

  66. Juguet M, Lautru S, Francou FX, Nezbedovà S, Leblond P, Gondry M, Pernodet J-L (2009) An iterative nonribosomal peptide synthetase assembles the pyrrole-amide antibiotic congocidine in Streptomyces ambofaciens. Chem Biol 16:421–431

    CAS  Google Scholar 

  67. Hur GH, Vickery CR, Burkart MD (2012) Explorations of catalytic domains in non-ribosomal peptide synthetase enzymology. Nat Prod Rep 29:1074–1098

    CAS  Google Scholar 

  68. Luo C, Liu X, Zhou X, Guo J, Truong J, Wang X, Xhou H, Li X, Chen Z (2015) Unusual biosynthesis and structure of locillomycins from Bacillus subtilis 916. Appl Environ Microbiol 81:6601–6609

    CAS  Google Scholar 

  69. Payne JAE, Schoppet M, Hansen MH, Cryle MJ (2017) Diversity of nature’s assembly lines-recent discoveries in non-ribosomal peptide synthesis. Mol BioSyst 13:9–22

    CAS  Google Scholar 

  70. Challis GL, Ravel J, Townsend CA (2000) Predictive, structure-based model of amino acid recognition by nonribosomal peptide synthetase adenylation domains. Chem Biol 7:211–224

    CAS  Google Scholar 

  71. Hancock REW, Chapple DS (1999) Peptide antibiotics. Antimicrob Agents Chemother 43:1317–1323

    CAS  Google Scholar 

  72. Challis GL, Naismith JH (2004) Structural aspects of non-ribosomal peptide biosynthesis. Curr Opin Struct Biol 14:748–756

    CAS  Google Scholar 

  73. Süssmuth RD, Mainz A (2017) Nonribosomal peptide synthesis — principles and prospects. Angew Chemie - Int Ed 56:3770–3821

    Google Scholar 

  74. Fischbach MA, Walsh CT (2006) Assembly-line enzymology for polyketide and nonribosomal peptide antibiotics: logic, machinery and mechanisms. Chem Rev 106:3468–3496

    CAS  Google Scholar 

  75. Baranašić D, Zucko J, Diminic J, Gacesa R, Long PF, Cullum J, Hranueli D, Starcevic A (2014) Predicting substrate specificity of adenylation domains of nonribosomal peptide synthetases and other protein properties by latent semantic indexing. J Ind Microbiol Biotechnol 41:461–467

    Google Scholar 

  76. Crosby J, Crump MP (2012) The structural role of the carrier protein - active controller or passive carrier. Nat Prod Rep 29:1111–1137

    CAS  Google Scholar 

  77. Miller BR, Gulick AM (2016) Structural biology of non-ribosomal peptide synthetases. Methods Mol Biol 1401:3–29

    CAS  Google Scholar 

  78. Hoffmanns K, Schneider-scherzers E, Kleinkauf H, Rainer Z (1994) Purification and characterization of eucaryotic alanine racemase acting as key enzyme in cyclosporin biosynthesis. J Biol Chem 269:12710–12714

    Google Scholar 

  79. Stein T, Kluge B, Vater J, Franke P, Otto A, Wittmann-Liebold B (1995) Gramicidin S synthetase 1 (phenylalanine racemase), a prototype of amino acid racemases containing the cofactor 4′-phosphopantetheinet. Biochem 34:4633–4642

    CAS  Google Scholar 

  80. Chatterjee J, Rechenmacher F, Kessler H (2013) N-Methylation of peptides and proteins: an important element for modulating biological functions. Angew Chem Int Ed Engl 52:254–269

    CAS  Google Scholar 

  81. Mori S, Pang AH, Lundy TA, Garzan A, Tsodikov OV, Garneau-Tsodikova S (2018) Structural basis for backbone N-methylation by an interrupted adenylation domain. Nat Chem Biol 14:428–430

    CAS  Google Scholar 

  82. Stachelhaus T, Marahiel MA (1995) Modular structure of genes encoding multifuctional peptide synthetases required for non-ribosomal peptide synthesis. FEMS Microbiol Lett 125:3–14

    CAS  Google Scholar 

  83. Du L, Sánchez C, Shen B (2001) Hybrid peptide-polyketide natural products: biosynthesis and prospects toward engineering novel molecules. Metab Eng 3:78–95

    CAS  Google Scholar 

  84. Smith S, Tsai SC (2007) The type I fatty acid and polyketide synthases: a tale of two megasynthases. Nat Prod Rep 24:1041–1072

    CAS  Google Scholar 

  85. Caulier S, Nannan C, Gillis A, Licciardi F, Bragard C, Mahillon J (2019) Overview of the antimicrobial compounds produced by members of the Bacillus subtilis group. Front Microbiol 10:1–19

    Google Scholar 

  86. Hertweck C (2009) The biosynthetic logic of polyketide diversity. Angew Chemie - Int Ed 48:4688–4716

    CAS  Google Scholar 

  87. Rawlings BJ (1997) Biosynthesis of polyketides. Nat Prod Rep 14:523–556

    CAS  Google Scholar 

  88. Cox RJ (2007) Polyketides, proteins and genes in fungi: programmed nano-machines begin to reveal their secrets. Org Biomol Chem 5:2010–2026

    CAS  Google Scholar 

  89. Schümann J, Hertweck C (2006) Advances in cloning, functional analysis and heterologous expression of fungal polyketide synthase genes. J Biotechnol 124:690–703

    Google Scholar 

  90. Chen H, Du L (2016) Iterative polyketide biosynthesis by modular polyketide synthases in bacteria. Appl Microbiol Biotechnol 100:541–557

    CAS  Google Scholar 

  91. Cane DE, Walsh CT, Khosla C (1998) Harnessing the biosynthetic code: combinations, permutations, and mutations. Science 282:63–68

    CAS  Google Scholar 

  92. Tang GL, Zhang Z, Pan HX (2017) New insights into bacterial type II polyketide biosynthesis. F1000Research 6: 1–12

  93. Staunton J, Weissman KJ (2001) Polyketide biosynthesis: a millennium review. Nat Prod Rep 18:380–416

    CAS  Google Scholar 

  94. Katsuyama Y, Ohnishi Y (2012) Type III polyketide synthases in microorganisms. 1st ed. Elsevier Inc.

  95. Sierra JM, Fusté E, Rabanal F, Vinuesa T, Viñas M (2017) An overview of antimicrobial peptides and the latest advances in their development. Expert Opin Biol Ther 17:663–676

    Google Scholar 

  96. Nakano C, Ozawa H, Akanuma G, Funa N, Hornouchi S (2009) Biosynthesis of aliphatic polyketides by type III Polyketide synthase and methyltransferase in Bacillus subtilis. J Bacteriol 191:4916–4923

    CAS  Google Scholar 

  97. Reimer D, Luxenberger E, Brachmann AO, Bode HB (2009) A new type of pyrrolidine biosynthesis is involved in the late steps of xenocoumacin production in Xenorhabdus nematophila. Chem Bio Chem 10:1997–2001

    CAS  Google Scholar 

  98. Chen G, Maxwell P, Dunphy GB, Webster JM (1996) Culture conditions for Xenorhabdus and Photorhabdus symbionts of entomopathogenic nematodes. Nematologica 42:127–130

    Google Scholar 

  99. Wang YH, Feng JT, Zhang Q, Zhang X (2008) Optimization of fermentation condition for antibiotic production by Xenorhabdus nematophila with response surface methodology. J Appl Microbiol 104:735–744

    CAS  Google Scholar 

  100. Sa-uth C, Rattanasena P, Chandrapatya A, Bussaman P (2018) Modification of medium composition for enhancing the production of antifungal activity from Xenorhabdus stockiae PB09 by using response surface methodology. Int J Microbiol 2018:1–10 https://www.hindawi.com/journals/ijmicro/2018/3965851/

    Google Scholar 

  101. Schimming O, Fleischhacker F, Nollmann FI, Bode HB (2014) Yeast homologous recombination cloning leading to the novel peptides ambactin and xenolindicin. Chem Bio Chem 15:1290–1294

    CAS  Google Scholar 

  102. Bode E, Brachmann AO, Kegler C, Simsek R, Dauth C, Zhou Q, Kaiser M, Klemmt P, Bode HB (2015) Simple ‘on-demand’ production of bioactive natural products. Chem Bio Chem 16:1115–1119

    CAS  Google Scholar 

  103. Engel Y, Windhorst C, Lu X, Goodrich-Blair H, Bode HB (2017) The global regulators Lrp, LeuO, and HexA control secondary metabolism in entomopathogenic bacteria. Front Microbiol 8:1–13

    Google Scholar 

  104. Wang Y, Fang X, Cheng Y, Zhang X (2011) Manipulation of pH shift to enhance the growth and antibiotic activity of Xenorhabdus nematophila. J Biomed Biotechnol 2011:1–9

    Google Scholar 

  105. Crawford JM, Kontnik R, Clardy J (2010) Regulating alternative lifestyles in entomopathogenic bacteria. Curr Biol 20:69–74

    CAS  Google Scholar 

  106. Wang Y, Fang X, An F, Wang G, Zhang X (2011) Improvement of antibiotic activity of Xenorhabdus bovienii by medium optimization using response surface methodology. Microb Cell Factories 10:1–15

    Google Scholar 

  107. Wang YH, Li YP, Zhang Q, Zhang X (2008) Enhanced antibiotic activity of Xenorhabdus nematophila by medium optimization. Bioresour Technol 99:1708–1715

    CAS  Google Scholar 

  108. Zhang Y, Werling U, Edelmann W (2012) SLiCE: a novel bacterial cell extract-based DNA cloning method. Nucleic Acids Res 40:1–10

    Google Scholar 

  109. Aslanidis C, de Jong PJ (1990) Ligation-independent cloning of PCR products (LIC-PCR). Nucleic Acids Res 18:6069–6074

    CAS  Google Scholar 

  110. Wenzel SC, Gross F, Zhang Y, Fu J, Stewart F, Müller R (2005) Heterologous expression of a myxobacterial natural products assembly line in Pseudomonas via Red/ET recombineering. Chem Biol 12:349–356

    CAS  Google Scholar 

  111. Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA, Smith H (2009) Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods 6:343–345

    CAS  Google Scholar 

  112. Ramjee MK, Petithory JR, McElver J, Weber SC, Kirsch JF (1996) A novel yeast expression/secretion system for the recombinant plant thiol endoprotease propapain. Protein Eng 9:1055–1061

    CAS  Google Scholar 

  113. Oldenburg KR, Vo KT, Michaelis S, Paddon C (1997) Recombination-mediated PCR-directed plasmid construction in vivo in yeast. Nucleic Acids Res 25:451–452

    CAS  Google Scholar 

  114. Yilmaz A, Grotewold E (2010) Components and mechanisms of regulation of gene expression. In: Ladunga I (ed) Computational biology of transcription factor binding, methods in molecular biology,1st ed. Humana Press, Totowa, NJ, pp 23–32

    Google Scholar 

  115. Heungens K, Cowles CE, Goodrich-Blair H (2002) Identification of Xenorhabdus nematophila genes required for mutualistic colonization of Steinernema carpocapsae nematodes. Mol Microbiol 45:1337–1353

    CAS  Google Scholar 

  116. Jubelin G, Lanois A, Severac D, Rialle S, Longin C, Gaudriault S, Givaudan A (2013) FliZ is a global regulatory protein affecting the expression of flagellar and virulence genes in individual Xenorhabdus nematophila bacterial cells. PLoS Genet 9:1–15

    Google Scholar 

  117. Cowles KN, Cowles CE, Richards GR, Martens EC, Goodrich-Blair H (2007) The global regulator Lrp contributes to mutualism, pathogenesis and phenotypic variation in the bacterium Xenorhabdus nematophila. Cell Microbiol 9:1311–1323

    CAS  Google Scholar 

  118. Hinchliffe SJ (2013) Insecticidal toxins from the Photorhabdus and Xenorhabdus bacteria. Open Toxinology J 3:101–118

    Google Scholar 

  119. Espinosa E, Casadesús J (2014) Regulation of Salmonella enterica pathogenicity island 1 (SPI-1) by the LysR-type regulator LeuO. Mol Microbiol 91:1057–1069

    CAS  Google Scholar 

  120. Bina XR, Taylor DL, Vikram A, Ante VM, Bine JE (2013) Vibrio cholerae ToxR downregulates virulence factor production in response to cyclo (Phe-pro). MBio 4:1–9

    Google Scholar 

  121. Whitaker WB, Parent MA, Boyd A, Richards GP, Boyd F (2012) The Vibrio parahaemolyticus ToxRS regulator is required for stress tolerance and colonization in a novel orogastric streptomycin-induced adult murine model. Infect Immun 80:1834–1845

    CAS  Google Scholar 

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This work was funded by a South African National Research Foundation grant.

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Booysen, E., Dicks, L.M.T. Does the Future of Antibiotics Lie in Secondary Metabolites Produced by Xenorhabdus spp.? A Review. Probiotics & Antimicro. Prot. 12, 1310–1320 (2020). https://doi.org/10.1007/s12602-020-09688-x

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