Chapter 18 : Chemical Biology Strategies for Biofilm Control

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Signaling pathways are required for bacterial biofilm formation and antimicrobial resistance. Among them, quorum sensing (QS) and c-di-GMP signaling are the best characterized. QS is a widely distributed intercellular signaling mechanism by which microorganisms regulate gene expression in response to small diffusible signaling molecules ( ). Bacteria have developed oligopeptides, -acyl homoserine lactones (HSLs), and autoinducer-2 as signal molecules ( ). When the QS signal molecules reach a local threshold concentration, they can interact with specific receptors and impact the expression of hundreds of genes. Many of the QS-regulated genes (motility, biosurfacant synthesis, EPS synthesis) are required for the biofilm formation and antibiotic resistance of various bacterial species ( ).

Citation: Yang L, Givskov M. 2015. Chemical Biology Strategies for Biofilm Control, p 363-372. In Ghannoum M, Parsek M, Whiteley M, Mukherjee P (ed), Microbial Biofilms, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MB-0019-2015
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Figure 1

Example of three QSIS systems. (A) In QSIS1, an engineered vector expressing the gene that encodes the toxic gene product under the control of LuxR was transformed to . (B) In QSIS2, the LasR-regulated promoter controls the expression of the gene, expression of which leads to cell death in the presence of sucrose. (C) The QSIS3 system is also based on LuxR regulation. The and genes, conferring kanamycin resistance and green fluorescence, respectively, are controlled by the repressor, which in turn is regulated by QS through the promoter. The system was established in . Figure adapted from Rasmussen et al. ( ) with permission of the publisher.

Citation: Yang L, Givskov M. 2015. Chemical Biology Strategies for Biofilm Control, p 363-372. In Ghannoum M, Parsek M, Whiteley M, Mukherjee P (ed), Microbial Biofilms, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MB-0019-2015
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Figure 2

Design and characterization of c-di-GMP biosensors. (a) Principle of synthesis and degradation of c-di-GMP by DGCs and PDEs. (b) Construction of the genetically encoded FRET-based biosensors for c-di-GMP using MrkH and VCA0042. Both proteins contain a c-di-GMP binding PilZ domain and an N-terminal domain (NTD). (c, d) Fluorescence titration curves for cdg-S1 and cdg-S2. (e) Schematic illustration of the conformational change induced by binding c-di-GMP to cdg-S1 and cdg-S2. Figure adapted from Ho et al. ( ) with permission of the publisher.

Citation: Yang L, Givskov M. 2015. Chemical Biology Strategies for Biofilm Control, p 363-372. In Ghannoum M, Parsek M, Whiteley M, Mukherjee P (ed), Microbial Biofilms, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MB-0019-2015
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