WO2001043739A1 - Inhibition of two-component signal transduction systems - Google Patents
Inhibition of two-component signal transduction systems Download PDFInfo
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- WO2001043739A1 WO2001043739A1 PCT/AU2000/001553 AU0001553W WO0143739A1 WO 2001043739 A1 WO2001043739 A1 WO 2001043739A1 AU 0001553 W AU0001553 W AU 0001553W WO 0143739 A1 WO0143739 A1 WO 0143739A1
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- 0 CCCCCC(*)C(C1OC1OC1=C*)=C1Br Chemical compound CCCCCC(*)C(C1OC1OC1=C*)=C1Br 0.000 description 2
- RCVCAVCJNJAFDX-ONEGZZNKSA-N C/C(/C(C)=O)=C\Br Chemical compound C/C(/C(C)=O)=C\Br RCVCAVCJNJAFDX-ONEGZZNKSA-N 0.000 description 1
- IZSIOOMKGJMBPZ-UHFFFAOYSA-N CC(C(O)O1)C(Br)=CC1=C(C)C Chemical compound CC(C(O)O1)C(Br)=CC1=C(C)C IZSIOOMKGJMBPZ-UHFFFAOYSA-N 0.000 description 1
- GWLDADMCKOCKLF-WEWOIACBSA-N CCC[C@H](C(C(O/C1=C\Br)=O)=C1Br)O Chemical compound CCC[C@H](C(C(O/C1=C\Br)=O)=C1Br)O GWLDADMCKOCKLF-WEWOIACBSA-N 0.000 description 1
- WZUQOHJFJKXIGN-UPHRSURJSA-N NC(C(O/C1=C\Br)=O)=C1Br Chemical compound NC(C(O/C1=C\Br)=O)=C1Br WZUQOHJFJKXIGN-UPHRSURJSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D9/00—Compositions of detergents based essentially on soap
- C11D9/04—Compositions of detergents based essentially on soap containing compounding ingredients other than soaps
- C11D9/22—Organic compounds, e.g. vitamins
- C11D9/26—Organic compounds, e.g. vitamins containing oxygen
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
- A01N43/08—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with oxygen as the ring hetero atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
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- A61K8/00—Cosmetics or similar toiletry preparations
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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- A61K8/37—Esters of carboxylic acids
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
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- A—HUMAN NECESSITIES
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/58—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
- A61K8/585—Organosilicon compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
- A61L2/18—Liquid substances or solutions comprising solids or dissolved gases
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- A61Q17/005—Antimicrobial preparations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/10—Washing or bathing preparations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/02—Preparations for cleaning the hair
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/0005—Other compounding ingredients characterised by their effect
- C11D3/0078—Compositions for cleaning contact lenses, spectacles or lenses
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/20—Organic compounds containing oxygen
- C11D3/2096—Heterocyclic compounds
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/48—Medical, disinfecting agents, disinfecting, antibacterial, germicidal or antimicrobial compositions
Definitions
- the present invention is directed generally to compositions and methods for inhibition of activities and actions of microorganisms, particularly inhibition of two-component signal transduction systems.
- Two-component signal transduction systems play important roles in the growth and maintenance and functionality of many different microorganisms. Examples include, but not are limited to, regulation of the production of exopolysaccharides and virulence factors; the regulation of motility, swarming, attachment and biofilm formation; and growth and maintenance of viability.
- Inhibitor A belonging to a class of isothiazalones, and Inhibitor B, a member of the quaternary imidazoles.
- Inhibitor A was shown to inhibit the autophosphorylation of the histidine protein kinase (HPK) AlgR2.
- Inhibitor B interfered with the binding of the response regulator (RR) AlgRl, in its phosphorylated form, to its target DNA promoter site, as determined in a gel mobility shift assay. The authors did not indicate whether the compounds reduced in vivo alginate production or had any antibacterial activity.
- Domagala et al. (1998) have identified another class of inhibitors of two-component signal transduction systems. This group screened for compounds that could de-phosphorylate the soluble HPK NRII in vitro, and identified a number of diphenolic methanes which showed significant activity. The compounds were also tested against two-component systems in vivo using Esche ⁇ chia coli and were demonstrated to be active. The assays used were of the authors' devising and were not described in great detail.
- RWJ-49815 and its analogues also proved to be potent Gram positive antibacterial compounds, active at concentrations of l-2 ⁇ g ml against S. aureus, E. faecium and Streptococcus pneumoniae.
- a second paper published by members of the same laboratory identified a further class of inhibitors of two-component systems, the substituted salicyanilides (Maclielag et al., 1998). In vitro tests using KinA and its RR partner SpoOF showed that these compounds inhibited the autophosphorylation of KinA.
- the authors also made use of an in vivo assay for two-component signal transduction based on the VanS VanR system.
- the salicyanilides had antibacterial effects against Gram positive organisms but had no effect on wild type E. coli. However, a mutant E. coli strain possessing a leaky outer membrane was as sensitive to the compounds as any of the Gram positive organisms tested.
- YycF Bacillus subtilis that is required for this organism's growth. When a thermosensitive mutant of YycF is grown at a nonpermissive temperature, growth rapidly ceases and empty cells are formed that retain their structural integrity.
- YycF belongs to the OmpR winged helix-turn-helix family of DNA- binding proteins and has a paired histidine protein kinase, YycG. Both members of this two-component signal transduction system are transcribed throughout the growth phase of B. subtilis but are not transcribed in stationary phase.
- the diphenolic methanes, hydrophobic tyramines and substituted salicyanilides have inhibitory effects on the in vivo activity of two- component signal transduction systems and also have strong growth inhibitory activity against Gram positives while having little effect on Gram negatives with intact outer membranes (Domagala et al., 1998; Barrett et al., 1998; Macielag et al., 1998).
- the present invention consists in a composition for use in inhibiting at least one phenotype of a microorganism, the composition comprising at least one compound of general formula I:
- Ri and R 2 are independently H, halogen, alkyl, alkoxy, oxoalkyl, alkenyl, aryl or arylalkyl whether unsubstituted or substituted, optionally interrupted by one or more heteroatoms, straight chain or branched chain, hydrophilic or fluorophilic;
- R 3 and R 4 are independently H, halogen, alkyl, aryl or arylalkyl, alkoxy, alkylsilyl;
- R ⁇ and R ⁇ are independently H, halogen, carboxyl, ester, formyl, cyano, alkyl, alkoxy, oxoalkyl, alkenyl, aryl or arylalkyl whether unsubstituted or substituted, optionally interrupted by one or more heteroatoms, straight chain or branched chain, hydrophilic or fluorophilic;
- X is a halogen
- R 5 is H, alkyl, alkenyl, alkynyl, alkene, alkyne, aryl, arylalkyl, whether unsubstituted or substituted, optionally interrupted by one or more heteroatoms, straight chain or branched chain, hydrophilic or fluorophilic.
- the present invention consists in a method of inhibiting at least one phenotype of a microorganism, the method comprising exposing the microorganism to a composition comprising at least one compound of general formula I:
- Ri and R 2 are independently H, halogen, alkyl, alkoxy, oxoalkyl, alkenyl, aryl or arylalkyl whether unsubstituted or substituted, optionally interrupted by one or more heteroatoms, straight chain or branched chain, hydrophilic or fluorophilic;
- R 3 and R 4 are independently H, halogen, alkyl, aryl or arylalkyl, alkoxy, alkylsilyl;
- Re and R 7 are independently H, halogen, carboxyl, ester, formyl, cyano, alkyl, alkoxy, oxoalkyl, alkenyl, aryl or arylalkyl whether unsubstituted or substituted, optionally interrupted by one or more heteroatoms, straight chain or branched chain, hydrophilic or fluorophilic;
- X is a halogen;
- R 5 is H, alkyl, alkenyl, alkynyl, alkene, alkyne, aryl, arylalkyl, whether unsubstituted or substituted, optionally interrupted by one or more heteroatoms, straight chain or branched chain, hydrophilic or fluorophilic.
- alkyl is taken to mean both straight chain alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tertiary butyl, and the like.
- the alkyl group is a lower alkyl of 1 to 6 carbon atoms.
- the alkyl group may optionally be substituted by one or more groups selected from alkyl, cycloalkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkynyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, haloalkenyloxy, nitro, amino, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroheterocyclyl, alkylamino, dialkylamino, alkenylamine, alkynylamino, acyl, alkenoyl, alkynoyl, acylamino, diacylamino, acyloxy, alkylsulfonyloxy, heterocyclyl, heterocycloxy, heterocyclamino, haloheterocyclyl, alkylsulfenyl, alkylcarbonyloxy, alkylthio, acylthio, phosphorus-
- alkoxy denotes straight chain or branched alkyloxy, preferably Ci- o alkoxy. Examples include methoxy, ethoxy, n-propoxy, isopropoxy and the different butoxy isomers.
- alkenyl denotes groups formed from straight chain, branched or mono- or polycyclic alkenes and polyene. Substituents include mono- or poly- unsaturated alkyl or cycloalkyl groups as previously defined, preferably C2-10 alkenyl.
- alkenyl examples include vinyl, allyl, 1 -methyl vinyl, butenyl, iso- butenyl, 3-methyl-2-butenyl, 1-pentenyl, cyclopentenyl, 1-methyl-cyclopentenyl, 1- hexenyl, 3-hexenyl, cyclohexenyl, 1-heptenyl, 3-heptenyl, 1-octenyl, cyclooctenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl, 1-decenyl, 3-decenyl, 1,3-butadienyl, 1- 4,pentadienyl, 1,3-cyclopentadienyl, 1,3-hexadienyl, 1,4-hexadienyl, 1,3- cyclohexadienyl, 1,4-cyclohexadienyl, 1,3-cycloheptadienyl, 1,3,5- cyclohept
- halogen denotes fluorine, chlorine, bromine or iodine, preferably bromine or fluorine.
- heteroatoms denotes O, N or S.
- acyl used either alone or in compound words such as “acyloxy”, “acylthio", “acylamino” or diacylamino” denotes an aliphatic acyl group and an acyl group containing a heterocyclic ring which is referred to as heterocyclic acyl, preferably a Ci-io alkanoyl.
- acyl examples include carbamoyl; straight chain or branched alkanoyl, such as formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl; alkoxycarbonyl, such as methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, t-pentyloxycarbonyl or heptyloxycarbonyl; cycloalkanecarbonyl such as cyclopropanecarbonyl cyclobutanecarbonyl, cyclopentanecarbonyl or cyclohexanecarbonyl; alkanesulfonyl, such as methanesulfonyl or ethanesulfonyl; alkoxysul
- the phenotype is controlled by a two- component signal transduction system.
- the two-component signal transduction system is selected from, but not limited to, those whose response regulator belongs to the FixJ/LuxR subfamily or the OmpR subfamily of response regulators.
- the phenotype of the microorganism is selected from the group consisting of growth, swarming/motility, biofilm formation, expression of virulence factors and combinations thereof.
- the microorganism is selected from the group consisting of Bacillus sp., Streptococcus sp., Helicobacter sp., Mycobacte ⁇ um sp, Staphylococcus sp, Enterobacter sp., Pseudomonas sp., and Bordatella sp.
- the microorganism is selected from the group consisting of Bacillus subtilis, Bacillus anthracis, Bacillus cereus, Bacillus licheniformus, Streptococcus pneumonia, Helicobacter pylori, Mycobacte ⁇ um tuberculosis, Staphylococcus aureus, Staphylococcus epidermis, Enterobacter faecalis, Pseudomonas syringae, Pseudomonas aeruginosa, and Bordatella pertusis.
- composition comprises at least one compound selected from the group consisting of compounds 2, 3, 4, 30, 33, 34, 80, 97 as set out in Table 1 and combinations thereof.
- the present invention consists in a method of preventing or reducing biofilm formation on a surface, the method comprising applying to the surface the composition of the first aspect of the present invention.
- the present invention consists in a method of treating bacterial infection or decreasing the severity of symptoms of bacterial infection in an animal, the method comprising administering to the animal an effective amount of the composition of the first aspect of the present invention.
- the composition of the present invention can be used in environmental, sanitary, veterinary, or medical applications where it is possible to effect the phenotype of a microorganism, particularly through inhibition of a two-component signal transduction system.
- a particular two- component signal transduction system maybe targeted by use or selection of the compound or mixture of compounds.
- a particular microorganism may be targeted by use or selection of the compound or mixture of compounds.
- Applications include, but are not limited to, inhibition of growth of microbial pathogens in environmental situations, reduction or prevention of microbial colonisation of medical media including washing solutions, ointments and the like, inhibition of microbial attachment to surfaces and subsequent biofilm formation, as active ingredients in antiseptics and disinfectants.
- compositions can be usefully incorporated in a varied range of compositions.
- the compounds can be incorporated in a range of personal care products such as deodorants, soaps, shampoos, dentifrices etc.
- the manufacture of such compositions is well known in the art and the compounds of formulae I and II or mixtures thereof can be simply included in these compositions in admixture.
- the ability of compositions comprising the compounds of formulae I and II or mixtures to inhibit phenotypes of a range of bacteria provides a number of useful applications of these compositions.
- the compositions may be formulated for pharmaceutical use with human and non- human animals.
- the compositions are formulated for topical application for use, for example, in application to wounds and the like. In this regard they may be directly incorporated into bandages and the like.
- compositions of the present invention will also find application in preventing or inhibiting biofilm formation.
- compositions will find application as washing solutions, particularly in contact lens cleaning compositions.
- a concentration of less than 25 ⁇ g/ml in vivo is sufficient to inhibit the normal function of a number of two-component signal transduction systems. It will be appreciated, however, that the concentration required may depend on a number of factors including the microorganism, the furanone compound(s) used, the two-component signal transduction system to be inhibited, and the formulation of the furanone into the product.
- Figure 1 shows the growth responses of Bacillus subtilis strain ATCC 6633 and NCTC 10073 to compound 2. The compound was added at 8-9 hours, as denoted by the arrows, after the cultures had been growing.
- B. subtilis has a two component system that, when deleted, results in lysis and cell death. Addition of the compounds to B. subtilis also results in the induction of cell lysis, which can be observed as a cessation of growth and even a decrease in optical density. Therefore, this data suggests that the compounds interfere with this two component system and cause cell death or prevent growth.
- Aspartate was added to side-arm flasks to give a final concentration of 3mM (aspartate stock solution made up in M9 salts).
- the test compound or mixtures of compounds were dissolved in ethanol and added to cultures to give the required final concentrations. Negative controls were prepared with equal volumes of ethanol. Cultures were then placed in a 37°C incubator and shaken for 4 hours (OD ⁇ l0 approximately 0.7) before being removed and put on ice. Samples were then removed for ⁇ -galactosidase assays carried out according to the method of Miller (1972).
- test compound or mixtures of compounds were dissolved in ethanol and added to cultures to give the required final concentrations. Equal volumes of ethanol were added to Cu 2+ negative and positive cultures. Cultures were incubated for 6.5 hours at room temperature with shaking before being placed on ice. Samples were then removed for ⁇ -galactosidase assays, ⁇ -galactosidase assays were carried out in the same manner as those for the Taz assay described above. The effect of furanone compound 3 on the CopS/CopR two component signal transduction system that regulates copper resistance in Pseudomonas syringae pv. syringae (Mills et al., 1993) was assessed.
- GacS/GacA Assay P. syringae var tomato BB27 was grown overnight in SWM media at room temperature. This culture was used to stab inoculate SWM plates made up with 0.4% agar and incubated at room temperature (20°C). The culture was also used to stab inoculate sets of SWM plates (0.4% agar) that had been made up with 25 ⁇ g/ml and 50 ⁇ g/ml of the test compound (stock solutions made up in ethanol). These plates were also incubated at room temperature for 36 hours before being examined for swarming activity and photographed. Before use all 0.4% agar SWM plates were allowed to air-dry for two hours in a laminar flow cabinet at room temperature.
- Furanone compound 3 was found to shut down swarming at 50 ⁇ g/ml and dramatically alters the swarming pattern at a concentration of 25 ⁇ g/ml.
- Compound 3 did not inhibit the growth of P. syringae var. tomato at a concentration of 50 ⁇ g/ml.
- Furanone compound 30 also inhibited the swarming response in P. syringae.
- Furanones as Inhibitors of Signal Transduction Systems Effects on the Colonisation of Surfaces Given that the furanones and related compounds of the present invention interfere with the normal function of two-component signal transduction systems, it may be that the furanones block the attachment of bacteria to the surface, by interfering with one or more of these systems. There is certainly some evidence that two-component signal transduction systems play a central role in the attachment of bacteria to surfaces.
- the ColS/ColR two-component signal transduction system in Pseudomonas fluorescens strain WCS365 plays an important role in the attachment of this bacterial strain to root surfaces (Dekkers et al., 1998).
- the CpxA/CpxR two- component system similarly regulates the expression of the csgA, thereby controlling the number of curli produced (Dorel et al., 1999).
- Other groups have demonstrated that structures on the surface of E. coli are important for attachment, for example Pratt and Kolter (1998) demonstrated that type I pili are required for E. coli strains to permanently attach to a surface, and it is likely that two-component signal transduction systems play some role in their regulation.
- VanS-VanR The VanS-VanR two- component regulatory system controls synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147. J. Bacteriol. 174: 2582-2591
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Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
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AU23284/01A AU2328401A (en) | 1999-12-17 | 2000-12-18 | Inhibition of two-component signal transduction systems |
EP00986856A EP1248611A4 (en) | 1999-12-17 | 2000-12-18 | Inhibition of two-component signal transduction systems |
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AUPQ4755 | 1999-12-17 | ||
AUPQ4755A AUPQ475599A0 (en) | 1999-12-17 | 1999-12-17 | Inhibition of two-component transduction systems |
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US10/954,288 Continuation US20050054722A1 (en) | 1999-12-17 | 2004-10-01 | Inhibition of two-component signal transduction systems |
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WO2001043739A1 true WO2001043739A1 (en) | 2001-06-21 |
Family
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PCT/AU2000/001553 WO2001043739A1 (en) | 1999-12-17 | 2000-12-18 | Inhibition of two-component signal transduction systems |
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US (2) | US20030125381A1 (en) |
EP (1) | EP1248611A4 (en) |
AU (1) | AUPQ475599A0 (en) |
WO (1) | WO2001043739A1 (en) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002047681A1 (en) * | 2000-12-14 | 2002-06-20 | Unisearch Limited | Regulation of bacterial virulence |
WO2002102370A1 (en) * | 2001-06-18 | 2002-12-27 | Unisearch Limited | Biofilm degrading or sloughing compositions and methods |
US6528472B2 (en) | 2000-11-17 | 2003-03-04 | S.C. Johnson & Son, Inc. | Antimicrobial compositions containing quaternary ammonium compounds, silanes and other disinfectants with furanones |
WO2003038026A1 (en) * | 2001-10-26 | 2003-05-08 | S. C. Johnson & Son, Inc. | Hard surface cleaners containing chitosan and furanone |
WO2005123645A1 (en) * | 2004-06-21 | 2005-12-29 | Biosignal Limited | Regulators of bacterial signalling pathways |
WO2006117113A2 (en) * | 2005-05-02 | 2006-11-09 | Henkel Kommanditgesellschaft Auf Aktien | Halomethylene alkanones and furanones for use as biofilm blocking substances |
US7642285B2 (en) | 2005-02-04 | 2010-01-05 | Wisconsin Alumni Research Foundation | Compounds and methods for modulating communication and virulence in quorum sensing bacteria |
US7910622B2 (en) | 2007-03-19 | 2011-03-22 | Wisconsin Alumni Research Foundation | Modulation of bacterial quorum sensing with synthetic ligands |
US8624063B2 (en) | 2009-06-30 | 2014-01-07 | Wisconsin Alumni Research Foundation | Non-lactone carbocyclic and heterocyclic antagonists and agonists of bacterial quorum sensing |
US10526278B2 (en) | 2017-10-19 | 2020-01-07 | Wisconsin Alumni Research Foundation | Inhibitors of quorum sensing receptor LasR |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7365184B2 (en) * | 2003-04-11 | 2008-04-29 | New York University | B. anthracis prevention and treatment: mutant B. anthracis lacking luxS activity and furanone inhibition of growth, AI-2 quorum sensing, and toxin production |
JP6366389B2 (en) * | 2014-07-03 | 2018-08-01 | 株式会社日本クライメイトシステムズ | Fan mounting structure |
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EP0067124A1 (en) * | 1981-06-05 | 1982-12-15 | Ciba-Geigy Ag | Production of 5,5-disubstituted 3-oxo-pent-4-enoic acids, their halides, esters, thioesters and amides; and their use in antifungal and antibacterial compositions |
AU708962B2 (en) * | 1995-03-23 | 1999-08-19 | Unisearch Limited | Methods for microbial regulation |
WO1999054323A1 (en) * | 1998-04-16 | 1999-10-28 | Unisearch Limited | Production of furanones |
WO1999053915A1 (en) * | 1998-04-17 | 1999-10-28 | Unisearch Limited | Inhibition of gram positive bacteria |
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AUPM666694A0 (en) * | 1994-07-06 | 1994-07-28 | Unisearch Limited | Natural antifouling compositions |
AUPN191295A0 (en) * | 1995-03-23 | 1995-04-27 | Unisearch Limited | Microbiocide or microbial regulator |
AUPO772097A0 (en) * | 1997-07-04 | 1997-07-31 | Aquaculture Crc Limited | Antifouling polymers |
AUPO821197A0 (en) * | 1997-07-24 | 1997-08-14 | Aquaculture Crc Limited | Antifouling of shellfish |
AUPQ629200A0 (en) * | 2000-03-16 | 2000-04-15 | Unisearch Limited | Microbial inhibitory compositions |
AUPQ841900A0 (en) * | 2000-06-28 | 2000-07-20 | Unisearch Limited | Synthesis of cyclic compounds |
-
1999
- 1999-12-17 AU AUPQ4755A patent/AUPQ475599A0/en not_active Abandoned
-
2000
- 2000-12-18 US US10/168,141 patent/US20030125381A1/en not_active Abandoned
- 2000-12-18 WO PCT/AU2000/001553 patent/WO2001043739A1/en not_active Application Discontinuation
- 2000-12-18 EP EP00986856A patent/EP1248611A4/en not_active Withdrawn
-
2004
- 2004-10-01 US US10/954,288 patent/US20050054722A1/en not_active Abandoned
Patent Citations (4)
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EP0067124A1 (en) * | 1981-06-05 | 1982-12-15 | Ciba-Geigy Ag | Production of 5,5-disubstituted 3-oxo-pent-4-enoic acids, their halides, esters, thioesters and amides; and their use in antifungal and antibacterial compositions |
AU708962B2 (en) * | 1995-03-23 | 1999-08-19 | Unisearch Limited | Methods for microbial regulation |
WO1999054323A1 (en) * | 1998-04-16 | 1999-10-28 | Unisearch Limited | Production of furanones |
WO1999053915A1 (en) * | 1998-04-17 | 1999-10-28 | Unisearch Limited | Inhibition of gram positive bacteria |
Non-Patent Citations (6)
Cited By (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6528472B2 (en) | 2000-11-17 | 2003-03-04 | S.C. Johnson & Son, Inc. | Antimicrobial compositions containing quaternary ammonium compounds, silanes and other disinfectants with furanones |
WO2002047681A1 (en) * | 2000-12-14 | 2002-06-20 | Unisearch Limited | Regulation of bacterial virulence |
WO2002102370A1 (en) * | 2001-06-18 | 2002-12-27 | Unisearch Limited | Biofilm degrading or sloughing compositions and methods |
WO2003038026A1 (en) * | 2001-10-26 | 2003-05-08 | S. C. Johnson & Son, Inc. | Hard surface cleaners containing chitosan and furanone |
US6794346B2 (en) | 2001-10-26 | 2004-09-21 | S.C. Johnson & Son, Inc. | Hard surface cleaners containing chitosan and furanone |
JP2008503450A (en) * | 2004-06-21 | 2008-02-07 | バイオシグナル リミテッド | Regulators of bacterial signaling pathways |
WO2005123645A1 (en) * | 2004-06-21 | 2005-12-29 | Biosignal Limited | Regulators of bacterial signalling pathways |
US7642285B2 (en) | 2005-02-04 | 2010-01-05 | Wisconsin Alumni Research Foundation | Compounds and methods for modulating communication and virulence in quorum sensing bacteria |
US8269024B2 (en) | 2005-02-04 | 2012-09-18 | Wisconsin Alumni Research Foundation | Compounds and methods for modulating communication and virulence in quorum sensing bacteria |
WO2006117113A2 (en) * | 2005-05-02 | 2006-11-09 | Henkel Kommanditgesellschaft Auf Aktien | Halomethylene alkanones and furanones for use as biofilm blocking substances |
WO2006117113A3 (en) * | 2005-05-02 | 2007-07-12 | Henkel Kgaa | Halomethylene alkanones and furanones for use as biofilm blocking substances |
US7910622B2 (en) | 2007-03-19 | 2011-03-22 | Wisconsin Alumni Research Foundation | Modulation of bacterial quorum sensing with synthetic ligands |
US8815943B2 (en) | 2007-03-19 | 2014-08-26 | Wisconsin Alumni Research Foundation | Modulation of bacterial quorum sensing with synthetic ligands |
US9796694B2 (en) | 2007-03-19 | 2017-10-24 | Wisconsin Alumni Research Foundation | Modulation of bacterial quorum sensing with synthetic ligands |
US8624063B2 (en) | 2009-06-30 | 2014-01-07 | Wisconsin Alumni Research Foundation | Non-lactone carbocyclic and heterocyclic antagonists and agonists of bacterial quorum sensing |
US9758472B2 (en) | 2009-06-30 | 2017-09-12 | Wisconsin Alumni Research Foundation | Non-lactone carbocyclic and heterocyclic antagonists and agonists of bacterial quorum sensing |
US10807943B2 (en) | 2009-06-30 | 2020-10-20 | Wisconsin Alumni Research Foundation | Non-lactone carbocyclic modulators of bacterial quorum sensing |
US10526278B2 (en) | 2017-10-19 | 2020-01-07 | Wisconsin Alumni Research Foundation | Inhibitors of quorum sensing receptor LasR |
Also Published As
Publication number | Publication date |
---|---|
EP1248611A1 (en) | 2002-10-16 |
AUPQ475599A0 (en) | 2000-01-20 |
US20050054722A1 (en) | 2005-03-10 |
US20030125381A1 (en) | 2003-07-03 |
EP1248611A4 (en) | 2003-05-21 |
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