Chapter 19 : A New Look at Secondary Metabolites

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In syntrophic interactions, metabolic pathways are integrated over different cell types. This chapter focuses on two seemingly well-defined groups of secondary metabolites, quorum-sensing signals and antibiotics, to demonstrate that their described biological activities do not necessarily define their functional roles in microbial communities. The study of the biology of living organisms and associated biochemical processes has, to date, focused primarily on the structures and functions of DNA, RNA, proteins, lipids, carbohydrates, and their macromolecular complexes. Many bacteria regulate gene expression in response to accumulation of secondary metabolites, and this behavior has been collectively referred to as quorum sensing or cell-cell communication. The generalization of quorum sensing as a density-dependent process ignores the reality that most bacteria do not exist in well-stirred reactors and the signaling will largely be a local event between small groups of cells. The dual role of quorum-sensing signal and antibiotic is not exclusive to nisin, subtilin, and mercascidin peptide antibiotics. A bactericidal activity produced by a strain of that inhibited the growth of several related strains was purified and demonstrated to be a typical acyl homoserine lactone (AHL) [-(3-hydroxy-7-cis-tetradecenoyl)-L-homoserine lactone]. The streptomycin and chloramphenicol resistance determinants were later shown to catalyze chemical inactivation of the corresponding antibiotic. In addition to the widespread occurrence of antibiotic resistance mechanisms, it has become apparent in recent years that there are many naturally occurring systems that interfere with cell-cell signaling pathways.

Citation: Surette M, Davies J. 2008. A New Look at Secondary Metabolites, p 307-322. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch19
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Hormesis and small molecules. The nature and extent of transcription responses to bioactive small molecules are concentration dependent. The cellular response at low concentration will be observed where there are no significant growth effects and can often be observed as changes in patterns of gene expression. The pattern of expressed genes will change when growth becomes inhibited. Reprinted from reference . © Elsevier (2006).

Citation: Surette M, Davies J. 2008. A New Look at Secondary Metabolites, p 307-322. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch19
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Image of FIGURE 2

Representative structures of small molecule signaling compounds. Two examples of -acyl homoserine lactones from : (A) 3-oxododecanoyl-homoserine lactone ( ) and (B) -butanoyl-homoserine lactone ( ). (C) The quinolone signal 2-heptyl-3-hydroxy-4-quinolone (PQS) ( ). Two examples of γ-butyrolactones: (D) factor 1 from ( ) and (E) IM-2 from ( ). (F) AI-2 is formed from 4,5-dihydroxy-2,3-pentanedione (DPD), the product generated by LuxS ( ), which spontaneously cyclizes into a family of furanones. (G) The furanosyl borate diester complex of (, )-2-methyl-2,3,3,4-tetrahy-droxytetrahydrofuran is the form of AI-2 bound to LuxP receptor of ( ). (H) The (, )-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran isomer interacts with the LsrB receptor in serovar Typhimurium ( ).

Citation: Surette M, Davies J. 2008. A New Look at Secondary Metabolites, p 307-322. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch19
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Image of FIGURE 3

Transcriptional response to subinhibitory antibiotics. serovar Typhimurium containing a promoter- fusion for an amino acid biosynthesis operon was plated on LB agar with antibiotics added to sterile filter disks as indicated in the first panel. The middle panel is a photograph of the plate after 20 h showing zones of inhibition. The third panel is a photograph taken in the dark showing strong induction of luciferase at subinhibitory concentrations for some but not all antibiotics. The dashed lines in this panel indicate the zone of inhibition for each antibiotic. The abbreviations for the antibiotics are Erm, erythromycin; Cam, chloramphenicol;Tet, tetracycline; Spc, spectinomycin; Nal, nalidixic acid; Str, streptomycin; Gat, gatifloxicin;Tmp, trimethoprim (J. Davies and M. G. Surette, unpublished data).

Citation: Surette M, Davies J. 2008. A New Look at Secondary Metabolites, p 307-322. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch19
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