Guest guest Posted March 29, 2007 Report Share Posted March 29, 2007 Excellent article! And right on. What Tony's been screaming forever. I could be evidence subject #1. Staph A. & Staph Epi along with pseudomonas...two of my main culprits which have attached to the bone in my jaw and sinuses. I hope they figure something out soon. They'd better. I'd never, ever have a dental implant or root canal, but with all the artificial implants, and dental work going on, along with joint replacements, etc., they're going to have to do something. The dental industry is responsible for a huge number of chronically ill people, imo, and I think some of the upper levels of the medical community and ADA know what's going on. But they don't want the public to know. I hope they're working hard to find an answer to the biofilm situation, if for no other reason than to keep themselves from going down in lawsuits, once people finally figure it out. It does seem that many of these biofilm studies are coming out of dental schools, which signals to me they know it's a big problem and only going to get bigger if something isn't done. If you have one of these recurring infections in an artificial joint (which is common), the docs know how to treat it and treat appropriately. It's still hard to eradicate, but they take extreme measures, i.v. abx, etc. There are probably millions of people with the exact same infections in their jaws and sinuses, and the care they get is barbaric compared to the kind of care you'd get if it was an artificial hip. penny Barb Peck <egroups1bp@...> wrote: Chemistry and IndustryFebruary 26, 2007Killer dialogue: when bacteria are told to do so they form biofilms on solid surfaces which reduce the effectiveness of antibiotics. Corfield looks at ways of inhibiting these instructions;BacteriaBYLINE: Corfield, SECTION: Pg. 24(2) No. 4 ISSN: 0009-3068LENGTH: 1564 wordsThe idea of alien intelligences calmly watching our every move anddiscussingthe right time to take the Earth from us is the stuff of books, movies and nightmares. But how would you feel if you knew thatevery time you sat in the dentist's chair your dentist was fighting a losing battle with exactly such afoe?One of the most startling discoveries to come out of the burgeoning world of microbiology in the past two decades is the fact that bacteria can communicate.In fact, not just communicate but converse on alevel where they can induce each other to switch on dormant genes that then have the capacity to do you harm.Dental plaque, it turns out, is the least of our worries. The superbug MRSA is part of the same phenomenon, called 'quorum sensing'.Quorum sensing is the ability of bacteria to communicate and coordinate behaviour using signalling molecules called autoinducers. Autoinducers are continuously produced by bacteria but when their concentration reaches a certain threshold--that is to say, when the bacteria producing it have a quorum--they switch on transcription genes withinthe bacteria's DNA telling it to do two things: to produce more autoinducer and, crucially, to change behaviour.It is the behaviour change that does the damage. Most bacteria spend their lives as free-swimming, planktonic organisms but when mandated to do so by the autoinducer will switch to a sessile lifestyle, dropping out of the swimming phase and anchoring to the nearest solid surface, be it a tooth, contact lens or the newly-minted plastic ball-joint of a hip replacement. There they formbiofilms--bacterial mats that reduce the effectiveness of antibiotics and where the local concentration of autoinducer goes through the roof. Once a biofilm is established it is very difficult to get rid of--witness the ubiquity of dental plaque and the dogged resistance of MRSA to treatment.Dietrich Mack at the University of Swansea and his group have beenactive in discovering just how quorum sensing works. In Staphylococcus aureus and S. epidermidis--the microbes responsible for both MRSA and implantation rejects--they have identified at least two major gene expression pathways responsible for initiating biofilm formation, one based on a polysaccharide and the other on a peptide. But as Mack acknowledges, 'Our research shows that the expression of these pathways is not straightforward. In certain cases where weinhibit a gene responsible involved in quorum sensing it can actually increase the amount of biofilm formed'.Quorum sensing, however, does more than merely initiate biofilm formation. It is a potent weapon of war between bacteria. For example, the four most common strains of S. aureus, including MRSA, use four slightly different autoinducers to initiate biofilm formation, all of which also aggressively inhibit the receptor sites of the other strains. The strain that reaches its critical quorum level first not only gets to put down its biofilm inducing roots first, it also gets to silence its competitors, preventing them from building up more of theirown autoinducer.Production of orthopaedic implants--from artificial hips to hip and knee joints--is an expanding industry worth $2.5bn in 2005 in Europe, according to Frost & Sullivan. Eighty per cent of hospital-acquired infections are associated with implants or other 'in-dwelling' medical devices, while 60% of hospital infections generally involve biofilms. Since MRSA and other biofilm-infections are frequently fatal, there are compelling financial and ethical reasons to find ways of preventing biofilm formation.Just how biofilms heighten resistance to antibiotics is not straightforward.It may be simply because the ability of antibiotics to penetrate the biofilm to the bacterial cells themselves is impaired, or it may be that the life-style change from planktonic to sessile changes the metabolic state of the bacterial cell and therefore its resistance to antibiotics. A more extreme suggestion is that the bacteria are fundamentally altered in some way so that they behave more like a multicellular tissue than a loose agglomeration of co-operating singlecells.For years, the approach to tackle biofilms has been incorporate antimicrobial agents in biomaterials that are to be used within the body, but the problem is the incredible ability of bacteria to develop antibiotic resistance. Because of their short generation time and their uncomplicated genomes, the fact is that bacteria can mutate and develop resistance faster than we can develop drugs to combat them. Simply killing bacteria in situ can lead to dead microbial cellsand associated detritus fouling the surfaces of crucial implants. Defeating biomaterial biofilm formation requires a different approach, one that does not result in the death of the bacterium but rather in the neutralisation of its malevolence.There are several possibilities: coating the biomaterial with substances that prevent bioadhesion, developing responsive surfaces that react to bacterial invasion, controlling the orientation of surface-tethered adhesion molecules, or interfering with receptor-ligand specific adhesion. But as Llinos and Geoff s of the AO Foundation in Davos, Switzerland, point out: 'no surface modification or coating fully prevents bacterial adhesion'.This leaves perhaps the most exciting possibility of all: disabling their quorum sensing mechanisms so that the bacteria cannot form biofilms in the first place.Several signal molecule families involved in quorum sensing have been identified in Gram-negative bacteria--those with two sets of cellmembranes--like Pseudomonas aeruginosa, but the most intensively studied is the N-acylhomoserine lactone (AHL) family. AHLs contain a homoserine lactone ring attached via an amide bond to an acyl side chaincontaining anything from four to 14 carbon atoms. Once the AHL reaches a critical threshold, concentration members of the LuxR and LuxN family of transcriptional activator genes are switched on, forming proteins that start binding the bacteria to the substrate, thereby beginning biofilm formation. Variations in the chain length and oxidation at the 3-position provide different Gram-negative bacteria with species-specific languages with which they can communicate with their own kind.Yet, since 75 Gram-negative bacterial species are known to use AHL, and only 25 AHL varieties have been found, it must also be the casethat some of these species share a common tongue and can therefore talk across species boundaries.Since biofilms usually consist of a multitude of different bacteriaspecies--which have different niches and therefore do not compete with each other--this implies that different bacteria co-operate in biofilm formation. It is a frightening thought.There is some good news, however. Some natural molecules have beenfound to interfere with AHL-mediated quorum sensing and the most important of these are halogenated furanones produced by the large marine alga Delisea pulchra.Halogenated furanones are structurally similar to AHLs and interfere with the ability of AHLs to bond to biomaterial surfaces. An analogy would be the way that carbon monoxide interferes with oxygen's ability to bond with haemoglobiny occupying the haemoglobin's receptor sites first.The Australian firm Biosignal is leading the way in the application of antibiofilm agents to contact lenses. Biosignal's compounds are based on the naturally occurring furanones from Delisea pulchra. As the trend toward long-wearing disposable contact lenses gathers momentum it is increasingly important to make sure that the lenses do not grow a biofilm and cause eye infection. An initial human safety trial of their furanone-based coating was completed last year and the results look positive. 'The potential market is enormous', says Oredsson, Biosignal's ceo, 'somewhere between $5bn and $6bn per year. We plan to levy a small but meaningful royalty on the use of Biosignal's proprietary technology--we aim for around 5%.'Gram-positive bacteria like S. aureus and Staphylococcus epidermidis--the major cause of implant biofilm infections--use peptides rather than AHLs as signal molecules. In S. epidermidis a single peptide, once it has reached its critical level, activates an accessory gene regulator (agr) operon that results in the synthesis of PolysaccharideIntercellular Adhesin (PIA), a molecular glue that starts the process of biofilm formation.An inhibiting peptide, appropriately known as RIP, can inhibit biofilm formation in both S. epidermidis and S. aureus and is under investigation as a potential treatment for Staphylococcus-induced infections.As yet, however, there is no magic bullet for preventing Gram-positive, quorum sensing-induced, biofilm formation, and scaling up thesetechniques to clinical level offers substantial technical challenges. When asked exactly how inhibition of quorum sensing can be used to stop MRSA biofilm formation,Dietrich Mack responded: 'That is a verygood question. I would like to know the answer to that too.'But there is everything left to play for. Oredsson acknowledges that contact lenses are just the tip of the iceberg, and that the impetus behind quorum sensing remains a cure for serious bacterial infections, including those caused y MRSA. Corfield is a science writer based in OxfordshireLOAD-DATE: March 27, 2007 McGiffertCampaign Managerwww.StopHospitalInfections.org512-477-4431 ext 115512-477-8934 fax Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 29, 2007 Report Share Posted March 29, 2007 My goodness I read some of this article and they got it exactly right. 'SWITCH ON SOME DORMANT JEANS'- the stuff steven johnsons syndrome is all about IMO.-I alway's believed that the bacteria teamning in us and all over us have got some serious ability waiting to be unleashed.I suppose Simply because they can destroy teeth when the conditions are right..NOw steven johnsons syndrome makes someone look like they have been attacked by a blowtorch when something, or someone, hits the right switch..The dingbats that form our back bone of intelligence call this an out of control immune response--Freakin Hogwash!!!! it's what bacteria do best- making substances in the chemical industry, cleaning up toxic sites by neutralising and eating stuff up .. basically having a huge role to play in our everyday life.. yet we are never subject to suffer toxemia, bacteremia, septicemia, this only happens to every other animal on the planet.. -- In infections , " Barb Peck " <egroups1bp@...> wrote: > > Chemistry and Industry > > February 26, 2007 > > Killer dialogue: when bacteria are told to do so they form biofilms > on solid surfaces which reduce the effectiveness of antibiotics. > Corfield looks at ways of inhibiting these instructions; > > Bacteria > > BYLINE: Corfield, > > SECTION: Pg. 24(2) No. 4 ISSN: 0009-3068 > > LENGTH: 1564 words > > > > The idea of alien intelligences calmly watching our every move > anddiscussing > > the right time to take the Earth from us is the stuff of books, > movies and nightmares. But how would you feel if you knew thatevery > time you sat in the dentist's chair your dentist was fighting a > losing battle with exactly such afoe? > > One of the most startling discoveries to come out of the > burgeoning world of microbiology in the past two decades is the fact > that bacteria can communicate. > > In fact, not just communicate but converse on alevel where they can > induce each other to switch on dormant genes that then have the > capacity to do you harm. > > Dental plaque, it turns out, is the least of our worries. The > superbug MRSA is part of the same phenomenon, called 'quorum sensing'. > > Quorum sensing is the ability of bacteria to communicate and > coordinate behaviour using signalling molecules called autoinducers. > Autoinducers are continuously produced by bacteria but when their > concentration reaches a certain threshold--that is to say, when the > bacteria producing it have a quorum--they switch on transcription > genes withinthe bacteria's DNA telling it to do two things: to > produce more autoinducer and, crucially, to change behaviour. > > It is the behaviour change that does the damage. Most bacteria > spend their lives as free-swimming, planktonic organisms but when > mandated to do so by the autoinducer will switch to a sessile > lifestyle, dropping out of the swimming phase and anchoring to the > nearest solid surface, be it a tooth, contact lens or the newly- > minted plastic ball-joint of a hip replacement. There they form > > biofilms--bacterial mats that reduce the effectiveness of antibiotics > and where the local concentration of autoinducer goes through the > roof. Once a biofilm is established it is very difficult to get rid > of--witness the ubiquity of dental plaque and the dogged resistance > of MRSA to treatment. > > Dietrich Mack at the University of Swansea and his group have > beenactive in discovering just how quorum sensing works. In > Staphylococcus aureus and S. epidermidis--the microbes responsible > for both MRSA and implantation rejects--they have identified at least > two major gene expression pathways responsible for initiating biofilm > formation, one based on a polysaccharide and the other on a peptide. > But as Mack acknowledges, 'Our research shows that the expression of > these pathways is not straightforward. In certain cases where > weinhibit a gene responsible involved in quorum sensing it can > actually increase the amount of biofilm formed'. > > Quorum sensing, however, does more than merely initiate biofilm > formation. It is a potent weapon of war between bacteria. For > example, the four most common strains of S. aureus, including MRSA, > use four slightly different autoinducers to initiate biofilm > formation, all of which also aggressively inhibit the receptor sites > of the other strains. > > The strain that reaches its critical quorum level first not only gets > to put down its biofilm inducing roots first, it also gets to silence > its competitors, preventing them from building up more of theirown > autoinducer. > > Production of orthopaedic implants--from artificial hips to hip > and knee joints--is an expanding industry worth $2.5bn in 2005 in > Europe, according to Frost & Sullivan. Eighty per cent of hospital- > acquired infections are associated with implants or other 'in- > dwelling' medical devices, while 60% of hospital infections generally > involve biofilms. Since MRSA and other biofilm-infections are > frequently fatal, there are compelling financial and ethical reasons > to find ways of preventing biofilm formation. > > Just how biofilms heighten resistance to antibiotics is not > straightforward. > > It may be simply because the ability of antibiotics to penetrate the > biofilm to the bacterial cells themselves is impaired, or it may be > that the life-style change from planktonic to sessile changes the > metabolic state of the bacterial cell and therefore its resistance to > antibiotics. A more extreme suggestion is that the bacteria are > fundamentally altered in some way so that they behave more like a > multicellular tissue than a loose agglomeration of co-operating single > > cells. > > For years, the approach to tackle biofilms has been incorporate > antimicrobial agents in biomaterials that are to be used within the > body, but the problem is the incredible ability of bacteria to > develop antibiotic resistance. Because of their short generation time > and their uncomplicated genomes, the fact is that bacteria can mutate > and develop resistance faster than we can develop drugs to combat > them. Simply killing bacteria in situ can lead to dead microbial cells > > and associated detritus fouling the surfaces of crucial implants. > Defeating biomaterial biofilm formation requires a different > approach, one that does not result in the death of the bacterium but > rather in the neutralisation of its malevolence. > > There are several possibilities: coating the biomaterial with > substances that prevent bioadhesion, developing responsive surfaces > that react to bacterial invasion, controlling the orientation of > surface-tethered adhesion molecules, or interfering with receptor- > ligand specific adhesion. But as Llinos and Geoff s of > the AO Foundation in Davos, Switzerland, point out: 'no surface > modification or coating fully prevents bacterial adhesion'. > This leaves perhaps the most exciting possibility of all: > disabling their quorum sensing mechanisms so that the bacteria cannot > form biofilms in the first place. > > Several signal molecule families involved in quorum sensing have > been identified in Gram-negative bacteria--those with two sets of > cellmembranes--like Pseudomonas aeruginosa, but the most intensively > studied is the N-acylhomoserine lactone (AHL) family. AHLs contain a > homoserine lactone ring attached via an amide bond to an acyl side > chaincontaining anything from four to 14 carbon atoms. > > Once the AHL reaches a critical threshold, concentration members > of the LuxR and LuxN family of transcriptional activator genes are > switched on, forming proteins that start binding the bacteria to the > substrate, thereby beginning biofilm formation. Variations in the > chain length and oxidation at the 3-position provide different Gram- > negative bacteria with species-specific languages with which they can > communicate with their own kind. > > Yet, since 75 Gram-negative bacterial species are known to use > AHL, and only 25 AHL varieties have been found, it must also be the > casethat some of these species share a common tongue and can > therefore talk across species boundaries. > > Since biofilms usually consist of a multitude of different bacteria > species--which have different niches and therefore do not compete > with each other--this implies that different bacteria co-operate in > biofilm formation. > > It is a frightening thought. > > There is some good news, however. Some natural molecules have > beenfound to interfere with AHL-mediated quorum sensing and the most > important of these are halogenated furanones produced by the large > marine alga Delisea pulchra. > > Halogenated furanones are structurally similar to AHLs and interfere > with the ability of AHLs to bond to biomaterial surfaces. An analogy > would be the way that carbon monoxide interferes with oxygen's > ability to bond with haemoglobin > y occupying the haemoglobin's receptor sites first. > > The Australian firm Biosignal is leading the way in the > application of antibiofilm agents to contact lenses. Biosignal's > compounds are based on the naturally occurring furanones from Delisea > pulchra. As the trend toward long-wearing disposable contact lenses > gathers momentum it is increasingly important to make sure that the > lenses do not grow a biofilm and cause eye infection. An initial > human safety trial of their furanone-based coating was completed last > year and the results look positive. 'The potential market is > enormous', says Oredsson, Biosignal's ceo, 'somewhere between > $5bn and $6bn per year. We plan to levy a small but meaningful > royalty on the use of Biosignal's proprietary technology--we aim for > around 5%.' > > Gram-positive bacteria like S. aureus and Staphylococcus > epidermidis--the major cause of implant biofilm infections--use > peptides rather than AHLs as signal molecules. In S. epidermidis a > single peptide, once it has reached its critical level, activates an > accessory gene regulator (agr) operon that results in the synthesis > of PolysaccharideIntercellular Adhesin (PIA), a molecular glue that > starts the process of biofilm formation. > > An inhibiting peptide, appropriately known as RIP, can inhibit > biofilm formation in both S. epidermidis and S. aureus and is under > investigation as a potential treatment for Staphylococcus-induced > infections. > > As yet, however, there is no magic bullet for preventing Gram- > positive, quorum sensing-induced, biofilm formation, and scaling up > thesetechniques to clinical level offers substantial technical > challenges. When asked exactly how inhibition of quorum sensing can > be used to stop MRSA biofilm formation, > > Dietrich Mack responded: 'That is a verygood question. I would like > to know the answer to that too.' > > But there is everything left to play for. Oredsson acknowledges > that contact lenses are just the tip of the iceberg, and that the > impetus behind quorum sensing remains a cure for serious bacterial > infections, including those caused y MRSA. > > Corfield is a science writer based in Oxfordshire > > LOAD-DATE: March 27, 2007 > > McGiffert > > Campaign Manager > > www.StopHospitalInfections.org > > 512-477-4431 ext 115 > > 512-477-8934 fax > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 29, 2007 Report Share Posted March 29, 2007 Reading more of that article you can tell me that herxing is good science when you have a quorum sensing/biofilm formation waiting to fry your arse...I scream and sound idiotic at times(more often than not) but this is the science I discovered coming from the back door to reach the front door to get a similar appreciation of all this... -- In infections , " Barb Peck " <egroups1bp@...> wrote: > > Chemistry and Industry > > February 26, 2007 > > Killer dialogue: when bacteria are told to do so they form biofilms > on solid surfaces which reduce the effectiveness of antibiotics. > Corfield looks at ways of inhibiting these instructions; > > Bacteria > > BYLINE: Corfield, > > SECTION: Pg. 24(2) No. 4 ISSN: 0009-3068 > > LENGTH: 1564 words > > > > The idea of alien intelligences calmly watching our every move > anddiscussing > > the right time to take the Earth from us is the stuff of books, > movies and nightmares. But how would you feel if you knew thatevery > time you sat in the dentist's chair your dentist was fighting a > losing battle with exactly such afoe? > > One of the most startling discoveries to come out of the > burgeoning world of microbiology in the past two decades is the fact > that bacteria can communicate. > > In fact, not just communicate but converse on alevel where they can > induce each other to switch on dormant genes that then have the > capacity to do you harm. > > Dental plaque, it turns out, is the least of our worries. The > superbug MRSA is part of the same phenomenon, called 'quorum sensing'. > > Quorum sensing is the ability of bacteria to communicate and > coordinate behaviour using signalling molecules called autoinducers. > Autoinducers are continuously produced by bacteria but when their > concentration reaches a certain threshold--that is to say, when the > bacteria producing it have a quorum--they switch on transcription > genes withinthe bacteria's DNA telling it to do two things: to > produce more autoinducer and, crucially, to change behaviour. > > It is the behaviour change that does the damage. Most bacteria > spend their lives as free-swimming, planktonic organisms but when > mandated to do so by the autoinducer will switch to a sessile > lifestyle, dropping out of the swimming phase and anchoring to the > nearest solid surface, be it a tooth, contact lens or the newly- > minted plastic ball-joint of a hip replacement. There they form > > biofilms--bacterial mats that reduce the effectiveness of antibiotics > and where the local concentration of autoinducer goes through the > roof. Once a biofilm is established it is very difficult to get rid > of--witness the ubiquity of dental plaque and the dogged resistance > of MRSA to treatment. > > Dietrich Mack at the University of Swansea and his group have > beenactive in discovering just how quorum sensing works. In > Staphylococcus aureus and S. epidermidis--the microbes responsible > for both MRSA and implantation rejects--they have identified at least > two major gene expression pathways responsible for initiating biofilm > formation, one based on a polysaccharide and the other on a peptide. > But as Mack acknowledges, 'Our research shows that the expression of > these pathways is not straightforward. In certain cases where > weinhibit a gene responsible involved in quorum sensing it can > actually increase the amount of biofilm formed'. > > Quorum sensing, however, does more than merely initiate biofilm > formation. It is a potent weapon of war between bacteria. For > example, the four most common strains of S. aureus, including MRSA, > use four slightly different autoinducers to initiate biofilm > formation, all of which also aggressively inhibit the receptor sites > of the other strains. > > The strain that reaches its critical quorum level first not only gets > to put down its biofilm inducing roots first, it also gets to silence > its competitors, preventing them from building up more of theirown > autoinducer. > > Production of orthopaedic implants--from artificial hips to hip > and knee joints--is an expanding industry worth $2.5bn in 2005 in > Europe, according to Frost & Sullivan. Eighty per cent of hospital- > acquired infections are associated with implants or other 'in- > dwelling' medical devices, while 60% of hospital infections generally > involve biofilms. Since MRSA and other biofilm-infections are > frequently fatal, there are compelling financial and ethical reasons > to find ways of preventing biofilm formation. > > Just how biofilms heighten resistance to antibiotics is not > straightforward. > > It may be simply because the ability of antibiotics to penetrate the > biofilm to the bacterial cells themselves is impaired, or it may be > that the life-style change from planktonic to sessile changes the > metabolic state of the bacterial cell and therefore its resistance to > antibiotics. A more extreme suggestion is that the bacteria are > fundamentally altered in some way so that they behave more like a > multicellular tissue than a loose agglomeration of co-operating single > > cells. > > For years, the approach to tackle biofilms has been incorporate > antimicrobial agents in biomaterials that are to be used within the > body, but the problem is the incredible ability of bacteria to > develop antibiotic resistance. Because of their short generation time > and their uncomplicated genomes, the fact is that bacteria can mutate > and develop resistance faster than we can develop drugs to combat > them. Simply killing bacteria in situ can lead to dead microbial cells > > and associated detritus fouling the surfaces of crucial implants. > Defeating biomaterial biofilm formation requires a different > approach, one that does not result in the death of the bacterium but > rather in the neutralisation of its malevolence. > > There are several possibilities: coating the biomaterial with > substances that prevent bioadhesion, developing responsive surfaces > that react to bacterial invasion, controlling the orientation of > surface-tethered adhesion molecules, or interfering with receptor- > ligand specific adhesion. But as Llinos and Geoff s of > the AO Foundation in Davos, Switzerland, point out: 'no surface > modification or coating fully prevents bacterial adhesion'. > This leaves perhaps the most exciting possibility of all: > disabling their quorum sensing mechanisms so that the bacteria cannot > form biofilms in the first place. > > Several signal molecule families involved in quorum sensing have > been identified in Gram-negative bacteria--those with two sets of > cellmembranes--like Pseudomonas aeruginosa, but the most intensively > studied is the N-acylhomoserine lactone (AHL) family. AHLs contain a > homoserine lactone ring attached via an amide bond to an acyl side > chaincontaining anything from four to 14 carbon atoms. > > Once the AHL reaches a critical threshold, concentration members > of the LuxR and LuxN family of transcriptional activator genes are > switched on, forming proteins that start binding the bacteria to the > substrate, thereby beginning biofilm formation. Variations in the > chain length and oxidation at the 3-position provide different Gram- > negative bacteria with species-specific languages with which they can > communicate with their own kind. > > Yet, since 75 Gram-negative bacterial species are known to use > AHL, and only 25 AHL varieties have been found, it must also be the > casethat some of these species share a common tongue and can > therefore talk across species boundaries. > > Since biofilms usually consist of a multitude of different bacteria > species--which have different niches and therefore do not compete > with each other--this implies that different bacteria co-operate in > biofilm formation. > > It is a frightening thought. > > There is some good news, however. Some natural molecules have > beenfound to interfere with AHL-mediated quorum sensing and the most > important of these are halogenated furanones produced by the large > marine alga Delisea pulchra. > > Halogenated furanones are structurally similar to AHLs and interfere > with the ability of AHLs to bond to biomaterial surfaces. An analogy > would be the way that carbon monoxide interferes with oxygen's > ability to bond with haemoglobin > y occupying the haemoglobin's receptor sites first. > > The Australian firm Biosignal is leading the way in the > application of antibiofilm agents to contact lenses. Biosignal's > compounds are based on the naturally occurring furanones from Delisea > pulchra. As the trend toward long-wearing disposable contact lenses > gathers momentum it is increasingly important to make sure that the > lenses do not grow a biofilm and cause eye infection. An initial > human safety trial of their furanone-based coating was completed last > year and the results look positive. 'The potential market is > enormous', says Oredsson, Biosignal's ceo, 'somewhere between > $5bn and $6bn per year. We plan to levy a small but meaningful > royalty on the use of Biosignal's proprietary technology--we aim for > around 5%.' > > Gram-positive bacteria like S. aureus and Staphylococcus > epidermidis--the major cause of implant biofilm infections--use > peptides rather than AHLs as signal molecules. In S. epidermidis a > single peptide, once it has reached its critical level, activates an > accessory gene regulator (agr) operon that results in the synthesis > of PolysaccharideIntercellular Adhesin (PIA), a molecular glue that > starts the process of biofilm formation. > > An inhibiting peptide, appropriately known as RIP, can inhibit > biofilm formation in both S. epidermidis and S. aureus and is under > investigation as a potential treatment for Staphylococcus-induced > infections. > > As yet, however, there is no magic bullet for preventing Gram- > positive, quorum sensing-induced, biofilm formation, and scaling up > thesetechniques to clinical level offers substantial technical > challenges. When asked exactly how inhibition of quorum sensing can > be used to stop MRSA biofilm formation, > > Dietrich Mack responded: 'That is a verygood question. I would like > to know the answer to that too.' > > But there is everything left to play for. Oredsson acknowledges > that contact lenses are just the tip of the iceberg, and that the > impetus behind quorum sensing remains a cure for serious bacterial > infections, including those caused y MRSA. > > Corfield is a science writer based in Oxfordshire > > LOAD-DATE: March 27, 2007 > > McGiffert > > Campaign Manager > > www.StopHospitalInfections.org > > 512-477-4431 ext 115 > > 512-477-8934 fax > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 30, 2007 Report Share Posted March 30, 2007 I thought this would be right up your alley.. It's like Christmas for me. I've just been bestowed upon with pertinent articles this past week on a few subjects (I have a GREAT one on Malaria - full paper conclusively showing that a low platelet count inficates RBC parsitemia better than any other parameter). > Chemistry and Industry > > February 26, 2007 > > Killer dialogue: when bacteria are told to do so they form biofilms > on solid surfaces which reduce the effectiveness of antibiotics. > Corfield looks at ways of inhibiting these instructions; > > Bacteria > > BYLINE: Corfield, > > SECTION: Pg. 24(2) No. 4 ISSN: 0009-3068 > > LENGTH: 1564 words > > The idea of alien intelligences calmly watching our every move > anddiscussing > > the right time to take the Earth from us is the stuff of books, > movies and nightmares. But how would you feel if you knew thatevery > time you sat in the dentist's chair your dentist was fighting a > losing battle with exactly such afoe? > > One of the most startling discoveries to come out of the > burgeoning world of microbiology in the past two decades is the fact > that bacteria can communicate. > > In fact, not just communicate but converse on alevel where they can > induce each other to switch on dormant genes that then have the > capacity to do you harm. > > Dental plaque, it turns out, is the least of our worries. The > superbug MRSA is part of the same phenomenon, called 'quorum sensing'. > > Quorum sensing is the ability of bacteria to communicate and > coordinate behaviour using signalling molecules called autoinducers. > Autoinducers are continuously produced by bacteria but when their > concentration reaches a certain threshold--that is to say, when the > bacteria producing it have a quorum--they switch on transcription > genes withinthe bacteria's DNA telling it to do two things: to > produce more autoinducer and, crucially, to change behaviour. > > It is the behaviour change that does the damage. Most bacteria > spend their lives as free-swimming, planktonic organisms but when > mandated to do so by the autoinducer will switch to a sessile > lifestyle, dropping out of the swimming phase and anchoring to the > nearest solid surface, be it a tooth, contact lens or the newly- > minted plastic ball-joint of a hip replacement. There they form > > biofilms--bacterial mats that reduce the effectiveness of antibiotics > and where the local concentration of autoinducer goes through the > roof. Once a biofilm is established it is very difficult to get rid > of--witness the ubiquity of dental plaque and the dogged resistance > of MRSA to treatment. > > Dietrich Mack at the University of Swansea and his group have > beenactive in discovering just how quorum sensing works. In > Staphylococcus aureus and S. epidermidis--the microbes responsible > for both MRSA and implantation rejects--they have identified at least > two major gene expression pathways responsible for initiating biofilm > formation, one based on a polysaccharide and the other on a peptide. > But as Mack acknowledges, 'Our research shows that the expression of > these pathways is not straightforward. In certain cases where > weinhibit a gene responsible involved in quorum sensing it can > actually increase the amount of biofilm formed'. > > Quorum sensing, however, does more than merely initiate biofilm > formation. It is a potent weapon of war between bacteria. For > example, the four most common strains of S. aureus, including MRSA, > use four slightly different autoinducers to initiate biofilm > formation, all of which also aggressively inhibit the receptor sites > of the other strains. > > The strain that reaches its critical quorum level first not only gets > to put down its biofilm inducing roots first, it also gets to silence > its competitors, preventing them from building up more of theirown > autoinducer. > > Production of orthopaedic implants--from artificial hips to hip > and knee joints--is an expanding industry worth $2.5bn in 2005 in > Europe, according to Frost & Sullivan. Eighty per cent of hospital- > acquired infections are associated with implants or other 'in- > dwelling' medical devices, while 60% of hospital infections generally > involve biofilms. Since MRSA and other biofilm-infections are > frequently fatal, there are compelling financial and ethical reasons > to find ways of preventing biofilm formation. > > Just how biofilms heighten resistance to antibiotics is not > straightforward. > > It may be simply because the ability of antibiotics to penetrate the > biofilm to the bacterial cells themselves is impaired, or it may be > that the life-style change from planktonic to sessile changes the > metabolic state of the bacterial cell and therefore its resistance to > antibiotics. A more extreme suggestion is that the bacteria are > fundamentally altered in some way so that they behave more like a > multicellular tissue than a loose agglomeration of co-operating single > > cells. > > For years, the approach to tackle biofilms has been incorporate > antimicrobial agents in biomaterials that are to be used within the > body, but the problem is the incredible ability of bacteria to > develop antibiotic resistance. Because of their short generation time > and their uncomplicated genomes, the fact is that bacteria can mutate > and develop resistance faster than we can develop drugs to combat > them. Simply killing bacteria in situ can lead to dead microbial cells > > and associated detritus fouling the surfaces of crucial implants. > Defeating biomaterial biofilm formation requires a different > approach, one that does not result in the death of the bacterium but > rather in the neutralisation of its malevolence. > > There are several possibilities: coating the biomaterial with > substances that prevent bioadhesion, developing responsive surfaces > that react to bacterial invasion, controlling the orientation of > surface-tethered adhesion molecules, or interfering with receptor- > ligand specific adhesion. But as Llinos and Geoff s of > the AO Foundation in Davos, Switzerland, point out: 'no surface > modification or coating fully prevents bacterial adhesion'. > This leaves perhaps the most exciting possibility of all: > disabling their quorum sensing mechanisms so that the bacteria cannot > form biofilms in the first place. > > Several signal molecule families involved in quorum sensing have > been identified in Gram-negative bacteria--those with two sets of > cellmembranes--like Pseudomonas aeruginosa, but the most intensively > studied is the N-acylhomoserine lactone (AHL) family. AHLs contain a > homoserine lactone ring attached via an amide bond to an acyl side > chaincontaining anything from four to 14 carbon atoms. > > Once the AHL reaches a critical threshold, concentration members > of the LuxR and LuxN family of transcriptional activator genes are > switched on, forming proteins that start binding the bacteria to the > substrate, thereby beginning biofilm formation. Variations in the > chain length and oxidation at the 3-position provide different Gram- > negative bacteria with species-specific languages with which they can > communicate with their own kind. > > Yet, since 75 Gram-negative bacterial species are known to use > AHL, and only 25 AHL varieties have been found, it must also be the > casethat some of these species share a common tongue and can > therefore talk across species boundaries. > > Since biofilms usually consist of a multitude of different bacteria > species--which have different niches and therefore do not compete > with each other--this implies that different bacteria co-operate in > biofilm formation. > > It is a frightening thought. > > There is some good news, however. Some natural molecules have > beenfound to interfere with AHL-mediated quorum sensing and the most > important of these are halogenated furanones produced by the large > marine alga Delisea pulchra. > > Halogenated furanones are structurally similar to AHLs and interfere > with the ability of AHLs to bond to biomaterial surfaces. An analogy > would be the way that carbon monoxide interferes with oxygen's > ability to bond with haemoglobin > y occupying the haemoglobin's receptor sites first. > > The Australian firm Biosignal is leading the way in the > application of antibiofilm agents to contact lenses. Biosignal's > compounds are based on the naturally occurring furanones from Delisea > pulchra. As the trend toward long-wearing disposable contact lenses > gathers momentum it is increasingly important to make sure that the > lenses do not grow a biofilm and cause eye infection. An initial > human safety trial of their furanone-based coating was completed last > year and the results look positive. 'The potential market is > enormous', says Oredsson, Biosignal's ceo, 'somewhere between > $5bn and $6bn per year. We plan to levy a small but meaningful > royalty on the use of Biosignal's proprietary technology--we aim for > around 5%.' > > Gram-positive bacteria like S. aureus and Staphylococcus > epidermidis--the major cause of implant biofilm infections--use > peptides rather than AHLs as signal molecules. In S. epidermidis a > single peptide, once it has reached its critical level, activates an > accessory gene regulator (agr) operon that results in the synthesis > of PolysaccharideIntercellular Adhesin (PIA), a molecular glue that > starts the process of biofilm formation. > > An inhibiting peptide, appropriately known as RIP, can inhibit > biofilm formation in both S. epidermidis and S. aureus and is under > investigation as a potential treatment for Staphylococcus-induced > infections. > > As yet, however, there is no magic bullet for preventing Gram- > positive, quorum sensing-induced, biofilm formation, and scaling up > thesetechniques to clinical level offers substantial technical > challenges. When asked exactly how inhibition of quorum sensing can > be used to stop MRSA biofilm formation, > > Dietrich Mack responded: 'That is a verygood question. I would like > to know the answer to that too.' > > But there is everything left to play for. Oredsson acknowledges > that contact lenses are just the tip of the iceberg, and that the > impetus behind quorum sensing remains a cure for serious bacterial > infections, including those caused y MRSA. > > Corfield is a science writer based in Oxfordshire > > LOAD-DATE: March 27, 2007 > > McGiffert > > Campaign Manager > > www.StopHospitalInfections.org > > 512-477-4431 ext 115 > > 512-477-8934 fax > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 30, 2007 Report Share Posted March 30, 2007 Nelly chiming in with low platelet counts and most probable Babesia infection, getting better on Lariam (albeit slowly and relapsing whenever I try stopping it) N. [infections] Re: More on BILOFILM I thought this would be right up your alley.. It's like Christmas for me.I've just been bestowed upon with pertinent articles this past week on a few subjects (I have a GREAT one on Malaria - full paper conclusively showing that a low platelet count inficates RBC parsitemia better than any other parameter).> Chemistry and Industry> > February 26, 2007> > Killer dialogue: when bacteria are told to do so they form biofilms > on solid surfaces which reduce the effectiveness of antibiotics. > Corfield looks at ways of inhibiting these instructions;> > Bacteria> > BYLINE: Corfield, > > SECTION: Pg. 24(2) No. 4 ISSN: 0009-3068> > LENGTH: 1564 words> > The idea of alien intelligences calmly watching our every move > anddiscussing> > the right time to take the Earth from us is the stuff of books, > movies and nightmares. But how would you feel if you knew thatevery > time you sat in the dentist's chair your dentist was fighting a > losing battle with exactly such afoe?> > One of the most startling discoveries to come out of the > burgeoning world of microbiology in the past two decades is the fact > that bacteria can communicate.> > In fact, not just communicate but converse on alevel where they can > induce each other to switch on dormant genes that then have the > capacity to do you harm.> > Dental plaque, it turns out, is the least of our worries. The > superbug MRSA is part of the same phenomenon, called 'quorum sensing'.> > Quorum sensing is the ability of bacteria to communicate and > coordinate behaviour using signalling molecules called autoinducers. > Autoinducers are continuously produced by bacteria but when their > concentration reaches a certain threshold--that is to say, when the > bacteria producing it have a quorum--they switch on transcription > genes withinthe bacteria's DNA telling it to do two things: to > produce more autoinducer and, crucially, to change behaviour.> > It is the behaviour change that does the damage. Most bacteria > spend their lives as free-swimming, planktonic organisms but when > mandated to do so by the autoinducer will switch to a sessile > lifestyle, dropping out of the swimming phase and anchoring to the > nearest solid surface, be it a tooth, contact lens or the newly-> minted plastic ball-joint of a hip replacement. There they form> > biofilms--bacterial mats that reduce the effectiveness of antibiotics > and where the local concentration of autoinducer goes through the > roof. Once a biofilm is established it is very difficult to get rid > of--witness the ubiquity of dental plaque and the dogged resistance > of MRSA to treatment.> > Dietrich Mack at the University of Swansea and his group have > beenactive in discovering just how quorum sensing works. In > Staphylococcus aureus and S. epidermidis--the microbes responsible > for both MRSA and implantation rejects--they have identified at least > two major gene expression pathways responsible for initiating biofilm > formation, one based on a polysaccharide and the other on a peptide. > But as Mack acknowledges, 'Our research shows that the expression of > these pathways is not straightforward. In certain cases where > weinhibit a gene responsible involved in quorum sensing it can > actually increase the amount of biofilm formed'.> > Quorum sensing, however, does more than merely initiate biofilm > formation. It is a potent weapon of war between bacteria. For > example, the four most common strains of S. aureus, including MRSA, > use four slightly different autoinducers to initiate biofilm > formation, all of which also aggressively inhibit the receptor sites > of the other strains. > > The strain that reaches its critical quorum level first not only gets > to put down its biofilm inducing roots first, it also gets to silence > its competitors, preventing them from building up more of theirown > autoinducer.> > Production of orthopaedic implants--from artificial hips to hip > and knee joints--is an expanding industry worth $2.5bn in 2005 in > Europe, according to Frost & Sullivan. Eighty per cent of hospital-> acquired infections are associated with implants or other 'in-> dwelling' medical devices, while 60% of hospital infections generally > involve biofilms. Since MRSA and other biofilm-infections are > frequently fatal, there are compelling financial and ethical reasons > to find ways of preventing biofilm formation.> > Just how biofilms heighten resistance to antibiotics is not > straightforward.> > It may be simply because the ability of antibiotics to penetrate the > biofilm to the bacterial cells themselves is impaired, or it may be > that the life-style change from planktonic to sessile changes the > metabolic state of the bacterial cell and therefore its resistance to > antibiotics. A more extreme suggestion is that the bacteria are > fundamentally altered in some way so that they behave more like a > multicellular tissue than a loose agglomeration of co-operating single> > cells.> > For years, the approach to tackle biofilms has been incorporate > antimicrobial agents in biomaterials that are to be used within the > body, but the problem is the incredible ability of bacteria to > develop antibiotic resistance. Because of their short generation time > and their uncomplicated genomes, the fact is that bacteria can mutate > and develop resistance faster than we can develop drugs to combat > them. Simply killing bacteria in situ can lead to dead microbial cells> > and associated detritus fouling the surfaces of crucial implants. > Defeating biomaterial biofilm formation requires a different > approach, one that does not result in the death of the bacterium but > rather in the neutralisation of its malevolence.> > There are several possibilities: coating the biomaterial with > substances that prevent bioadhesion, developing responsive surfaces > that react to bacterial invasion, controlling the orientation of > surface-tethered adhesion molecules, or interfering with receptor-> ligand specific adhesion. But as Llinos and Geoff s of > the AO Foundation in Davos, Switzerland, point out: 'no surface > modification or coating fully prevents bacterial adhesion'.> This leaves perhaps the most exciting possibility of all: > disabling their quorum sensing mechanisms so that the bacteria cannot > form biofilms in the first place.> > Several signal molecule families involved in quorum sensing have > been identified in Gram-negative bacteria--those with two sets of > cellmembranes--like Pseudomonas aeruginosa, but the most intensively > studied is the N-acylhomoserine lactone (AHL) family. AHLs contain a > homoserine lactone ring attached via an amide bond to an acyl side > chaincontaining anything from four to 14 carbon atoms. > > Once the AHL reaches a critical threshold, concentration members > of the LuxR and LuxN family of transcriptional activator genes are > switched on, forming proteins that start binding the bacteria to the > substrate, thereby beginning biofilm formation. Variations in the > chain length and oxidation at the 3-position provide different Gram-> negative bacteria with species-specific languages with which they can > communicate with their own kind.> > Yet, since 75 Gram-negative bacterial species are known to use > AHL, and only 25 AHL varieties have been found, it must also be the > casethat some of these species share a common tongue and can > therefore talk across species boundaries.> > Since biofilms usually consist of a multitude of different bacteria> species--which have different niches and therefore do not compete > with each other--this implies that different bacteria co-operate in > biofilm formation. > > It is a frightening thought.> > There is some good news, however. Some natural molecules have > beenfound to interfere with AHL-mediated quorum sensing and the most > important of these are halogenated furanones produced by the large > marine alga Delisea pulchra.> > Halogenated furanones are structurally similar to AHLs and interfere > with the ability of AHLs to bond to biomaterial surfaces. An analogy > would be the way that carbon monoxide interferes with oxygen's > ability to bond with haemoglobin> y occupying the haemoglobin's receptor sites first.> > The Australian firm Biosignal is leading the way in the > application of antibiofilm agents to contact lenses. Biosignal's > compounds are based on the naturally occurring furanones from Delisea > pulchra. As the trend toward long-wearing disposable contact lenses > gathers momentum it is increasingly important to make sure that the > lenses do not grow a biofilm and cause eye infection. An initial > human safety trial of their furanone-based coating was completed last > year and the results look positive. 'The potential market is > enormous', says Oredsson, Biosignal's ceo, 'somewhere between > $5bn and $6bn per year. We plan to levy a small but meaningful > royalty on the use of Biosignal's proprietary technology--we aim for > around 5%.'> > Gram-positive bacteria like S. aureus and Staphylococcus > epidermidis--the major cause of implant biofilm infections--use > peptides rather than AHLs as signal molecules. In S. epidermidis a > single peptide, once it has reached its critical level, activates an > accessory gene regulator (agr) operon that results in the synthesis > of PolysaccharideIntercellular Adhesin (PIA), a molecular glue that > starts the process of biofilm formation.> > An inhibiting peptide, appropriately known as RIP, can inhibit > biofilm formation in both S. epidermidis and S. aureus and is under > investigation as a potential treatment for Staphylococcus-induced > infections.> > As yet, however, there is no magic bullet for preventing Gram-> positive, quorum sensing-induced, biofilm formation, and scaling up > thesetechniques to clinical level offers substantial technical > challenges. When asked exactly how inhibition of quorum sensing can > be used to stop MRSA biofilm formation,> > Dietrich Mack responded: 'That is a verygood question. I would like > to know the answer to that too.'> > But there is everything left to play for. Oredsson acknowledges > that contact lenses are just the tip of the iceberg, and that the > impetus behind quorum sensing remains a cure for serious bacterial > infections, including those caused y MRSA.> > Corfield is a science writer based in Oxfordshire> > LOAD-DATE: March 27, 2007> > McGiffert> > Campaign Manager> > www.StopHospitalInfections.org> > 512-477-4431 ext 115> > 512-477-8934 fax> Quote Link to comment Share on other sites More sharing options...
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