
Full text loading...
Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis
Quorum-Sensing Inhibition, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555815578/9781555814045_Chap25-1.gif /docserver/preview/fulltext/10.1128/9781555815578/9781555814045_Chap25-2.gifAbstract:
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 Delisea pulchra 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 Pseudomonas aeruginosa 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.
Full text loading...
Halogenated furanone compounds. (A) Compound 1 and (B) compound 2 produced by the algae D. pulchra. Synthetic furanone compounds 30 (C) and 56 (D) ( 43 , 53 , 54 , 68 ).
The two QSIs, penicillic acid (A) and patulin, (B) produced by certain fungi ( 98 ).
Concentration-dependent inhibition of QS by furanone 30. P. aeruginosa harboring a lasB-gfp fusion is treated with different concentrations of the furanone (as indicated). Specific activity of gene expression fluorescence per OD600 is monitored over time.
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 (PQS) 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 PQS 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 ( 96 ).
AHL analogues with changes in the side chain. (A) 3-oxo-C6-HSL signal molecule. (B to D) Analogues with agonist effect. (E to H) Analogues with antagonistic effect. (I and J) Analogues without any effect ( 14 , 41 , 93 , 103 , 109 ).
AHL analogues with changes in the ring. (A) 3-oxo- C6 HSL signal molecule. (B) Analogue with agonist effect. (C) Analogue with antagonistic effect, (D to G) Analogues without any effect ( 87 , 109 ).
AHL analogues with exchanged ring part. (A) 3-oxo-C12-HSL 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. ( 84 , 85 , 115 , 116 ).
Molecules with QSI properties. (A) 2,4,5-tri-bromo-imidazole, (B) indole, (C) 3-nitrobenzene-sulfonamide, (D) 4-nitro-pyridine-N-oxide ( 96 ), and (E) compound 3 ( 106 ).
Proposed pathway of C4-HSL degradation ( 66 ). The molecules of the side chain are channeled into cell material, whereas the ring part is converted into a waste product.
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.