Small Molecules for Interference with Cell-Cell-Communication Systems in Gram-Negative Bacteria

Janssens, J.; Keersmaecker, Sigrid C. J. De; Vos, Dirk De; Vanderleyden, Jos

doi:10.2174/092986708785747580

Cited by 42 publications

(33 citation statements)

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“…The discovery that bacteria employ signal transduction pathways comprising molecules to globally regulate biofilm formation offers a novel target for biofilm control [134,135].…”

Section: Microbial Interactions/metabolite Moleculesmentioning

confidence: 99%

Antimicrobial Strategies Effective Against Infectious Bacterial Biofilms

Simões

2011

CMC

117

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Bacteria are able to adapt to undesirable changes in nutrient availability, environmental conditions and presence of antimicrobial products, as well as to immunological defenses. One particularly important example of bacterial adaptation is the ability to grow as part of a sessile community, commonly referred to as biofilm. It is a natural tendency of microorganisms to attach to biotic or abiotic surfaces, to multiply and to embed themselves in a slimy matrix, resulting in biofilms. Biofilms are the leading example of physiological adaptation and are one of the most important sources of bacterial resistance to antimicrobials. It is now recognized that most bacterial-associated infections, including endocarditis, dental caries, middle ear infections, osteomyelitis, medical device-related infections and chronic lung infections in cystic fibrosis patients are problematic because of biofilms. Bacteria in biofilms demonstrate intrinsic resistance to antimicrobial stress more effectively than the planktonic counterparts. Antimicrobial concentrations necessary to inhibit bacterial biofilms can be up to 10-1000 times higher than those needed to inhibit the same bacteria grown planktonically. Thus, in the presence of therapeutically available antibiotic concentrations biofilms remain viable after treatment. Therefore, the identification of new antimicrobials that inhibit or destroy biofilms is needed. The aim of this review is to cover the recent advances on the studies of antimicrobial strategies effective against infectious bacterial biofilms, including the current developments in the structure-activity relationship of those effective antimicrobials.

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“…The discovery that bacteria employ signal transduction pathways comprising molecules to globally regulate biofilm formation offers a novel target for biofilm control [134,135].…”

Section: Microbial Interactions/metabolite Moleculesmentioning

confidence: 99%

Antimicrobial Strategies Effective Against Infectious Bacterial Biofilms

Simões

2011

CMC

117

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“…A large number of studies have been carried out to investigate the effects of quorum sensing inhibitors and their potential applications in disease control (3,25). For example, for the opportunistic human pathogen Pseudomonas aeruginosa, various quorum sensing inhibitors have been identified, some of which are found to be effective in mitigating P. aeruginosa infection in murine models (4,18,22,24,38,53).…”

Section: Expression Of 5411 and 5906 In Tx1 Has Multiple Effects (I)mentioning

confidence: 99%

Attenuation ofEdwardsiella tardaVirulence by Small Peptides That Interfere with LuxS/Autoinducer Type 2 Quorum Sensing

Zhang

Jiao

et al. 2009

Appl Environ Microbiol

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Edwardsiella tarda is a gram-negative pathogen with a broad host range that includes humans, animals, and fish. Recent studies have shown that the LuxS/autoinducer type 2 (AI-2) quorum sensing system is involved in the virulence of E. tarda. In the present study, it was found that the E. tarda LuxS mutants bearing deletions of the catalytic site (C site) and the tyrosine kinase phosphorylation site, respectively, are functionally inactive and that these dysfunctional mutants can interfere with the activity of the wild-type LuxS. Two small peptides, 5411 and 5906, which share sequence identities with the C site of LuxS, were identified. 5411 and 5906 proved to be inhibitors of AI-2 activity and could vitiate the infectivity of the pathogenic E. tarda strain TX1. The inhibitory effect of 5411 and 5906 on AI-2 activity is exerted on LuxS, with which these peptides specifically interact. The expression of 5411 and 5906 in TX1 has multiple effects (altering biofilm production and the expression of certain virulence-associated genes), which are similar to those caused by interruption of luxS expression. Further study found that it is very likely that 5411 and 5906 can be released from the strains expressing them and, should TX1 be in the vicinity, captured by TX1. Based on this observation, a constitutive 5411 producer (Pseudomonas sp. strain FP3/pT5411) was constructed in the form of a fish commensal isolate that expresses 5411 from a plasmid source. The presence of FP3/pT5411 in fish attenuates the virulence of TX1. Finally, it was demonstrated that fish expressing 5411 directly from tissues exhibit enhanced resistance against TX1 infection.

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“…The 1 H NMR (300 MHz or 400 MHz) and 13 C NMR (75 MHz or 100 MHz) spectra were recorded with a Brucker ALS300, DRX300, and DRX400 spectrometers. Chemical shifts are given in ppm.…”

Section: Chain Length Compoundsmentioning

confidence: 99%

“…Compound 14d (129 mg, 70%) was obtained as a white solid from 9 (100 mg, 0.4 mmol) and 1-bromodecane (267 ll, 13 …”

Section: -Fluorenyl-3-decyl Imidazol-3-ium Bromide (14d)mentioning

confidence: 99%

“…Consequently QS inhibition has been considered as a possible strategy to fight pathogenic bacteria, encouraging in the last decades, numerous studies focusing either on the biological or the chemical points of view. [10][11][12][13][14][15][16][17][18][19] In Gram negative bacteria, the autoinducers are mainly N-acyl homoserine lactones (AHLs) and the transcriptional factors are LuxR-type proteins. 19 As part of our research aimed at the discovery of potential modulators of AHLs-dependent transcriptional regulators, [20][21][22][23][24][25] we recently described the computer aided identification of several inhibitors of LuxR dependent quorum sensing, all structurally unrelated to AHL.…”

Section: Introductionmentioning

confidence: 99%

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