Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes Controlled by Quorum Sensing

Jakobsen, Tim Holm; Gennip, Maria van; Phipps, Richard Kerry; Shanmugham, M. Sundaram; Christensen, Linda; Alhede, Morten; Skindersoe, Mette E.; Rasmussen, Trine Bernholdt; Friedrich, Karlheinz; Uthe, Friedrich; Jensen, Peter Østrup; Moser, Claus; Nielsen, Kristian Fog; Eberl, Leo; Larsen, Thomas Ostenfeld; Tanner, David; Høiby, Niels; Bjarnsholt, Thomas; Givskov, Michael

doi:10.1128/aac.05919-11

Cited by 382 publications

(264 citation statements)

References 77 publications

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“…This system has been heavily used to identify potential anti-biofilm agents, by measuring the reduction in surface attached biomass on the sides of wells after treatment with potential therapeutic agents [51][52][53][54]. In addition to this, The Center for Disease Control (CDC) approved biofilm reactor [55][56][57], and drip flow reactors, have proved excellent for assessing biofilm formation on biological and non-biological materials [58][59][60].…”

Section: In Vitro Investigation Of Biofilmsmentioning

confidence: 99%

The Limitations of In Vitro Experimentation in Understanding Biofilms and Chronic Infection

Roberts

Kragh

Bjarnsholt

et al. 2015

Journal of Molecular Biology

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168

153

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We have become increasingly aware that during infection, pathogenic bacteria often grow in multicellular biofilms which are often highly resistant to antibacterial strategies. In order to understand how biofilms form and contribute to infection, in vitro biofilm systems such as microtitre plate assays and flow cells, have been heavily used by many research groups around the world. Whilst these methods have greatly increased our understanding of the biology of biofilms, it is becoming increasingly apparent that many of our in vitro methods do not accurately represent in vivo conditions. Here we present a systematic review of the most widely used in vitro biofilm systems, and we discuss why they are not always representative of the in vivo biofilms found in chronic infections. We present examples of methods that will help us to bridge the gap between in vitro and in vivo biofilm work, so that our bench-side data can ultimately be used to improve bedside treatment.

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Section: In Vitro Investigation Of Biofilmsmentioning

confidence: 99%

The Limitations of In Vitro Experimentation in Understanding Biofilms and Chronic Infection

Roberts

Kragh

Bjarnsholt

et al. 2015

Journal of Molecular Biology

Self Cite

168

153

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“…Extracts of fruits (e.g., blackberries, cranberries, vanilla, and citrus) and herbs (e.g., rosemary and turmeric) and extracts and oils of other plant materials (garlic, clove, and cinnamon) and medicinal plants (e.g., betel nut and notoginsing) have all displayed QSI activity to some degree, typically found via inhibition of violacein production in the C. violaceum bioassay (137,138,(264)(265)(266)(267)(268)(269)(270)(271)(272)(273)(274)(275). In very few cases, however, have individual compounds been isolated or identified from these kinds of complex sources.…”

Section: Natural-product Qs Inhibitorsmentioning

confidence: 99%

“…From horseradish, the isothiocyanate iberin (Table 3) was identified and shown by transcriptome profiling to substantially inhibit expression of LasR-and RhlR-regulated genes in P. aeruginosa (137). From garlic extracts, an allyl sulfide called ajoene (Table 3) was isolated using the activity monitored by the QSIS reporter system (138,139). Interestingly, ajoene specifically affected a narrow set of QS-regulated genes in P. aeruginosa, including those involved in rhamnolipid production, and thus prevented P. aeruginosa biofilms from killing polymorphonuclear leukocytes in flow chambers, an effect attributable to rhamnolipid production (138,139).…”

Section: Natural-product Qs Inhibitorsmentioning

confidence: 99%

“…From garlic extracts, an allyl sulfide called ajoene (Table 3) was isolated using the activity monitored by the QSIS reporter system (138,139). Interestingly, ajoene specifically affected a narrow set of QS-regulated genes in P. aeruginosa, including those involved in rhamnolipid production, and thus prevented P. aeruginosa biofilms from killing polymorphonuclear leukocytes in flow chambers, an effect attributable to rhamnolipid production (138,139). Additionally, ajoene, as well as the furanone C-30, was shown to synergize with the antibiotic tobramycin in killing of P. aeruginosa biofilms and to improve clearance of P. aeruginosa from lungs in a mouse model of pulmonary infection (138,139).…”

Section: Natural-product Qs Inhibitorsmentioning

confidence: 99%

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Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

676

556

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SUMMARY Cell-cell communication, or quorum sensing, is a widespread phenomenon in bacteria that is used to coordinate gene expression among local populations. Its use by bacterial pathogens to regulate genes that promote invasion, defense, and spread has been particularly well documented. With the ongoing emergence of antibiotic-resistant pathogens, there is a current need for development of alternative therapeutic strategies. An antivirulence approach by which quorum sensing is impeded has caught on as a viable means to manipulate bacterial processes, especially pathogenic traits that are harmful to human and animal health and agricultural productivity. The identification and development of chemical compounds and enzymes that facilitate quorum-sensing inhibition (QSI) by targeting signaling molecules, signal biogenesis, or signal detection are reviewed here. Overall, the evidence suggests that QSI therapy may be efficacious against some, but not necessarily all, bacterial pathogens, and several failures and ongoing concerns that may steer future studies in productive directions are discussed. Nevertheless, various QSI successes have rightfully perpetuated excitement surrounding new potential therapies, and this review highlights promising QSI leads in disrupting pathogenesis in both plants and animals.

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“…Recent studies have shown that ajoene 2 is an effective QS inhibitor against Pseudomonas aeruginosa and Staphylococcus aureus and could be utilized for the treatment of chronic biofilm infections by exploiting the QS system 13. In this study, we employed a reporter strain ( Pseudomonas aeruginosa Pa01 lasB‐gfp )13a whereby QS gene expression was monitored over time in response to ajoene treatment.…”

mentioning

confidence: 99%