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Chapter 25 : Quorum-Sensing Inhibition

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Abstract:

As the elucidation of the molecular mechanisms behind quorum sensing (QS) gained momentum, researchers conceived several strategies to block QS systems. Indeed, QS signals can be detected in biofilms across a range of environments. For example, biofilms grown on rocks in the San Marcos River in Texas have been shown to produce acyl-homoserine lactone (AHL) signals, as have biofilm communities on marine snow particles and sponge surfaces. One of the major problems with conventional biofilm-control measures is the development of resistance. The red seaweed produces a range of halogenated furanone compounds that display antifouling and antimicrobial properties, altering the abundance and composition of the bacterial community on the surface and hence the subsequent development of a biofouling community. Transcriptomic analysis of gene expression shows that 4-nitro-pyridine-N-oxide (4-NPO) mainly affects genes that are regulated by either RhlR alone or RhlR and LasR in concert. A recent transcriptomic analysis strongly suggests that the wild-type further activates a QS-controlled strategic defense system, which reacts upon the encounter with polymorphonuclear leukocytes (PMNs) and suppresses the powerful cellular immune response by paralyzing the PMNs. Since the transcriptomic studies of in vitro biofilms suggest the existence of multiple pathways by which a biofilm can be built, the use and administration of QS blocking technologies may undergo further development and be combined with treatments directed at targets in additional pathways instrumental for biofilm development.

Citation: Kjelleberg S, McDougald D, Rasmussen T, Givskov M. 2008. Quorum-Sensing Inhibition, p 393-416. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch25

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Figures

Image of FIGURE 1
FIGURE 1

Halogenated furanone compounds. (A) Compound 1 and (B) compound 2 produced by the algae . Synthetic furanone compounds 30 (C) and 56 (D) ( ).

Citation: Kjelleberg S, McDougald D, Rasmussen T, Givskov M. 2008. Quorum-Sensing Inhibition, p 393-416. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch25
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Image of FIGURE 2
FIGURE 2

The two QSIs, penicillic acid (A) and patulin, (B) produced by certain fungi ( ).

Citation: Kjelleberg S, McDougald D, Rasmussen T, Givskov M. 2008. Quorum-Sensing Inhibition, p 393-416. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch25
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Image of FIGURE 3
FIGURE 3

Concentration-dependent inhibition of QS by furanone 30. harboring a fusion is treated with different concentrations of the furanone (as indicated). Specific activity of gene expression fluorescence per OD is monitored over time.

Citation: Kjelleberg S, McDougald D, Rasmussen T, Givskov M. 2008. Quorum-Sensing Inhibition, p 393-416. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch25
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Image of FIGURE 4
FIGURE 4

Principle of the QSIS system. (A) The screening bacteria are grown without AHL. The LuxR homologue is not activated; hence, there is no expression from the QS-controlled promoter (P) and the killing gene is not expressed. This condition is used when the bacteria are grown for purposes other than screening. (B) Exogenously added AHL molecules activate the P promoter, and the killing gene is thereby expressed, causing growth arrest of the bacteria. (C) Presence of an exogenously added QSI compound blocks QS, and the killing gene is not expressed, which rescues the host bacteria ( ).

Citation: Kjelleberg S, McDougald D, Rasmussen T, Givskov M. 2008. Quorum-Sensing Inhibition, p 393-416. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch25
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Image of FIGURE 5
FIGURE 5

AHL analogues with changes in the side chain. (A) 3-oxo-C-HSL signal molecule. (B to D) Analogues with agonist effect. (E to H) Analogues with antagonistic effect. (I and J) Analogues without any effect ( ).

Citation: Kjelleberg S, McDougald D, Rasmussen T, Givskov M. 2008. Quorum-Sensing Inhibition, p 393-416. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch25
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Image of FIGURE 6
FIGURE 6

AHL analogues with changes in the ring. (A) 3-oxo- C HSL signal molecule. (B) Analogue with agonist effect. (C) Analogue with antagonistic effect, (D to G) Analogues without any effect ( ).

Citation: Kjelleberg S, McDougald D, Rasmussen T, Givskov M. 2008. Quorum-Sensing Inhibition, p 393-416. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch25
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Image of FIGURE 7
FIGURE 7

AHL analogues with exchanged ring part. (A) 3-oxo-CHSL signal molecule and (B) analogue showing agonist effects. (C and D) Analogues with antagonistic effects from Smith et al. and (E and F) from Muh et al. ( ).

Citation: Kjelleberg S, McDougald D, Rasmussen T, Givskov M. 2008. Quorum-Sensing Inhibition, p 393-416. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch25
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Image of FIGURE 8
FIGURE 8

Molecules with QSI properties. (A) 2,4,5-tri-bromo-imidazole, (B) indole, (C) 3-nitrobenzene-sulfonamide, (D) 4-nitro-pyridine--oxide ( ), and (E) compound 3 ( ).

Citation: Kjelleberg S, McDougald D, Rasmussen T, Givskov M. 2008. Quorum-Sensing Inhibition, p 393-416. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch25
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Image of FIGURE 9
FIGURE 9

Proposed pathway of C-HSL degradation ( ). The molecules of the side chain are channeled into cell material, whereas the ring part is converted into a waste product.

Citation: Kjelleberg S, McDougald D, Rasmussen T, Givskov M. 2008. Quorum-Sensing Inhibition, p 393-416. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch25
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Image of FIGURE 10
FIGURE 10

The general structure of the series 1.5-dihydropyrrol-2-ones of a novel class of furanone-derived nontoxic QSI. The functional groups are as follows: R1 = H; R2 = alkyl, aryl; R3 = R4 = H. Br; R5 = H, aryl.

Citation: Kjelleberg S, McDougald D, Rasmussen T, Givskov M. 2008. Quorum-Sensing Inhibition, p 393-416. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch25
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