1887

Abstract

Reuterin is an antimicrobial compound produced by , and has been proposed to mediate, in part, the probiotic health benefits ascribed to this micro-organism. Despite 20 years of investigation, the mechanism of action by which reuterin exerts its antimicrobial effects has remained elusive. Here we provide evidence that reuterin induces oxidative stress in cells, most likely by modifying thiol groups in proteins and small molecules. cells subjected to sublethal levels of reuterin expressed a set of genes that overlapped with the set of genes composing the OxyR regulon, which senses and responds to various forms of oxidative stress. cells mutated for were more sensitive to reuterin compared with wild-type cells, further supporting a role for reuterin in exerting oxidative stress. The addition of cysteine to or growth media prior to exposure to reuterin suppressed the antimicrobial effect of reuterin on these bacteria. Interestingly, interaction with stimulated reuterin production or secretion by , indicating that contact with other microbes in the gut increases reuterin output. Thus, reuterin inhibits bacterial growth by modifying thiol groups, which indicates that reuterin negatively affects a large number of cellular targets.

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2010-06-01
2019-08-23
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References

  1. Arques, J. L., Fernandez, J., Gaya, P., Nunez, M., Rodriguez, E. & Medina, M. ( 2004; ). Antimicrobial activity of reuterin in combination with nisin against food-borne pathogens. Int J Food Microbiol 95, 225–229.[CrossRef]
    [Google Scholar]
  2. Arques, J. L., Rodriguez, E., Nunez, M. & Medina, M. ( 2008; ). Antimicrobial activity of nisin, reuterin, and the lactoperoxidase system on Listeria monocytogenes and Staphylococcus aureus in cuajada, a semisolid dairy product manufactured in Spain. J Dairy Sci 91, 70–75.[CrossRef]
    [Google Scholar]
  3. Baba, T., Ara, T., Hasegawa, M., Takai, Y., Okumura, Y., Baba, M., Datsenko, K. A., Tomita, M., Wanner, B. L. & Mori, H. ( 2006; ). Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol Syst Biol 2, 2006.0008
    [Google Scholar]
  4. Bergholz, T. M., Wick, L. M., Qi, W., Riordan, J. T., Ouellette, L. M. & Whittam, T. S. ( 2007; ). Global transcriptional response of Escherichia coli O157 : H7 to growth transitions in glucose minimal medium. BMC Microbiol 7, 97 [CrossRef]
    [Google Scholar]
  5. Britton, R. A. ( 2003; ). DNA microarrays and bacterial gene expression. Methods Enzymol 370, 264–278.
    [Google Scholar]
  6. Britton, R. A., Eichenberger, P., Gonzalez-Pastor, J. E., Fawcett, P., Monson, R., Losick, R. & Grossman, A. D. ( 2002; ). Genome-wide analysis of the stationary-phase sigma factor (sigma-H) regulon of Bacillus subtilis. J Bacteriol 184, 4881–4890.[CrossRef]
    [Google Scholar]
  7. Christman, M. F., Morgan, R. W., Jacobson, F. S. & Ames, B. N. ( 1985; ). Positive control of a regulon for defenses against oxidative stress and some heat-shock proteins in Salmonella typhimurium. Cell 41, 753–762.[CrossRef]
    [Google Scholar]
  8. Chung, T. C., Axelsson, L., Lindgren, S. E. & Dobrogosz, W. J. ( 1989; ). In vitro studies on reuterin synthesis by Lactobacillus reuteri. Microb Ecol Health Dis 2, 137–144.[CrossRef]
    [Google Scholar]
  9. Circle, S. J., Stone, L. & Boruff, C. S. ( 1945; ). Acrolein determination by means of tryptophan. Ind Eng Chem Res 17, 259–262.
    [Google Scholar]
  10. Cleusix, V., Lacroix, C., Vollenweider, S., Duboux, M. & Le Blay, G. ( 2007; ). Inhibitory activity spectrum of reuterin produced by Lactobacillus reuteri against intestinal bacteria. BMC Microbiol 7, 101 [CrossRef]
    [Google Scholar]
  11. Datsenko, K. A. & Wanner, B. L. ( 2000; ). One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 97, 6640–6645.[CrossRef]
    [Google Scholar]
  12. Dean, D. R., Hoch, J. A. & Aronson, A. I. ( 1977; ). Alteration of the Bacillus subtilis glutamine synthetase results in overproduction of the enzyme. J Bacteriol 131, 981–987.
    [Google Scholar]
  13. Doleyres, Y., Beck, P., Vollenweider, S. & Lacroix, C. ( 2005; ). Production of 3-hydroxypropionaldehyde using a two-step process with Lactobacillus reuteri. Appl Microbiol Biotechnol 68, 467–474.[CrossRef]
    [Google Scholar]
  14. Ellman, G. L. ( 1959; ). Tissue sulfhydryl groups. Arch Biochem Biophys 82, 70–77.[CrossRef]
    [Google Scholar]
  15. Floch, M. H., Walker, W. A., Guandalini, S., Hibberd, P., Gorbach, S., Surawicz, C., Sanders, M. E., Garcia-Tsao, G., Quigley, E. M. & other authors ( 2008; ). Recommendations for probiotic use – 2008. J Clin Gastroenterol 42 (Suppl. 2), S104–S108.[CrossRef]
    [Google Scholar]
  16. Kandler, O., Setter, K. O. & Kohl, R. ( 1980; ). Lactobacillus reuteri sp. nov., a new species of heterofermentative lactobacilli. Zentralbl Bakteriol Mikrobiol Hyg Abt 1 Orig C1, 264–269.
    [Google Scholar]
  17. Lin, Y. P., Thibodeaux, C. H., Pena, J. A., Ferry, G. D. & Versalovic, J. ( 2008; ). Probiotic Lactobacillus reuteri suppress proinflammatory cytokines via c-Jun. Inflamm Bowel Dis 14, 1068–1083.[CrossRef]
    [Google Scholar]
  18. Luthi-Peng, Q., Dileme, F. B. & Puhan, Z. ( 2002; ). Effect of glucose on glycerol bioconversion by Lactobacillus reuteri. Appl Microbiol Biotechnol 59, 289–296.[CrossRef]
    [Google Scholar]
  19. Marco, M. L., Pavan, S. & Kleerebezem, M. ( 2006; ). Towards understanding molecular modes of probiotic action. Curr Opin Biotechnol 17, 204–210.[CrossRef]
    [Google Scholar]
  20. Morita, H., Toh, H., Fukuda, S., Horikawa, H., Oshima, K., Suzuki, T., Murakami, M., Hisamatsu, S., Kato, Y. & other authors ( 2008; ). Comparative genome analysis of Lactobacillus reuteri and Lactobacillus fermentum reveal a genomic island for reuterin and cobalamin production. DNA Res 15, 151–161.[CrossRef]
    [Google Scholar]
  21. O'Hara, A. M. & Shanahan, F. ( 2007; ). Mechanisms of action of probiotics in intestinal diseases. ScientificWorldJournal 7, 31–46.[CrossRef]
    [Google Scholar]
  22. Perez, J. M., Arenas, F. A., Pradenas, G. A., Sandoval, J. M. & Vasquez, C. C. ( 2008; ). Escherichia coli YqhD exhibits aldehyde reductase activity and protects from the harmful effect of lipid peroxidation-derived aldehydes. J Biol Chem 283, 7346–7353.[CrossRef]
    [Google Scholar]
  23. Rosenfeldt, V., Michaelsen, K. F., Jakobsen, M., Larsen, C. N., Møller, P. L., Pedersen, P., Tvede, M., Weyrehter, H., Valerius, N. H. & Paerregaard, A. ( 2002a; ). Effect of probiotic Lactobacillus strains in young children hospitalized with acute diarrhea. Pediatr Infect Dis J 21, 411–416.[CrossRef]
    [Google Scholar]
  24. Rosenfeldt, V., Michaelsen, K. F., Jakobsen, M., Larsen, C. N., Moller, P. L., Tvede, M., Weyrehter, H., Valerius, N. H. & Paerregaard, A. ( 2002b; ). Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers. Pediatr Infect Dis J 21, 417–419.[CrossRef]
    [Google Scholar]
  25. Russell, W. M. & Klaenhammer, T. R. ( 2001; ). Efficient system for directed integration into the Lactobacillus acidophilus and Lactobacillus gasseri chromosomes via homologous recombination. Appl Environ Microbiol 67, 4361–4364.[CrossRef]
    [Google Scholar]
  26. Savino, F., Pelle, E., Palumeri, E., Oggero, R. & Miniero, R. ( 2007; ). Lactobacillus reuteri (American Type Culture Collection Strain 55730) versus simethicone in the treatment of infantile colic: a prospective randomized study. Pediatrics 119, e124–e130.[CrossRef]
    [Google Scholar]
  27. Schauer, D. B. & Falkow, S. ( 1993; ). The eae gene of Citrobacter freundii biotype 4280 is necessary for colonization in transmissible murine colonic hyperplasia. Infect Immun 61, 4654–4661.
    [Google Scholar]
  28. Spinler, J. K., Taweechotipatr, M., Rognerud, C. L., Ou, C. N., Tumwasorn, S. & Versalovic, J. ( 2008; ). Human-derived probiotic Lactobacillus reuteri demonstrate antimicrobial activities targeting diverse enteric bacterial pathogens. Anaerobe 14, 166–171.[CrossRef]
    [Google Scholar]
  29. Sriramulu, D. D., Liang, M., Hernandez-Romero, D., Raux-Deery, E., Lunsdorf, H., Parsons, J. B., Warren, M. J. & Prentice, M. B. ( 2008; ). Lactobacillus reuteri DSM 20016 produces cobalamin-dependent diol dehydratase in metabolosomes and metabolizes 1,2-propanediol by disproportionation. J Bacteriol 190, 4559–4567.[CrossRef]
    [Google Scholar]
  30. Talarico, T. L. & Dobrogosz, W. J. ( 1989; ). Chemical characterization of an antimicrobial substance produced by Lactobacillus reuteri. Antimicrob Agents Chemother 33, 674–679.[CrossRef]
    [Google Scholar]
  31. Talarico, T. L., Casas, I. A., Chung, T. C. & Dobrogosz, W. J. ( 1988; ). Production and isolation of reuterin, a growth inhibitor produced by Lactobacillus reuteri. Antimicrob Agents Chemother 32, 1854–1858.[CrossRef]
    [Google Scholar]
  32. Uicker, W. C., Schaefer, L. & Britton, R. A. ( 2006; ). The essential GTPase RbgA (YlqF) is required for 50S ribosome assembly in Bacillus subtilis. Mol Microbiol 59, 528–540.[CrossRef]
    [Google Scholar]
  33. Vollenweider, S. & Lacroix, C. ( 2004; ). 3-Hydroxypropionaldehyde: applications and perspectives of biotechnological production. Appl Microbiol Biotechnol 64, 16–27.[CrossRef]
    [Google Scholar]
  34. Vollenweider, S., Grassi, G., Konig, I. & Puhan, Z. ( 2003; ). Purification and structural characterization of 3-hydroxypropionaldehyde and its derivatives. J Agric Food Chem 51, 3287–3293.[CrossRef]
    [Google Scholar]
  35. Walter, J., Chagnaud, P., Tannock, G. W., Loach, D. M., Dal Bello, F., Jenkinson, H. F., Hammes, W. P. & Hertel, C. ( 2005; ). A high-molecular-mass surface protein (Lsp) and methionine sulfoxide reductase B (MsrB) contribute to the ecological performance of Lactobacillus reuteri in the murine gut. Appl Environ Microbiol 71, 979–986.[CrossRef]
    [Google Scholar]
  36. Weizman, Z., Asli, G. & Alsheikh, A. ( 2005; ). Effect of a probiotic infant formula on infections in child care centers: comparison of two probiotic agents. Pediatrics 115, 5–9.
    [Google Scholar]
  37. Whitehead, K., Versalovic, J., Roos, S. & Britton, R. A. ( 2008; ). Genomic and genetic characterization of the bile stress response of probiotic Lactobacillus reuteri ATCC 55730. Appl Environ Microbiol 74, 1812–1819.[CrossRef]
    [Google Scholar]
  38. Wickens, K., Black, P. N., Stanley, T. V., Mitchell, E., Fitzharris, P., Tannock, G. W., Purdie, G. & Crane, J. ( 2008; ). A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 122, 788–794.[CrossRef]
    [Google Scholar]
  39. Zhang, X. S., Garcia-Contreras, R. & Wood, T. K. ( 2007; ). YcfR (BhsA) influences Escherichia coli biofilm formation through stress response and surface hydrophobicity. J Bacteriol 189, 3051–3062.[CrossRef]
    [Google Scholar]
  40. Zheng, M., Wang, X., Templeton, L. J., Smulski, D. R., LaRossa, R. A. & Storz, G. ( 2001; ). DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide. J Bacteriol 183, 4562–4570.[CrossRef]
    [Google Scholar]
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vol. , part 6, pp. 1589 - 1599

genes induced and repressed upon exposure to reuterin [PDF](44 KB)



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