Molecule Could Prevent Biofilm

[Guest guest]

HEADLINE: Molecule Could Prevent Biofilm

Researchers at the University at Buffalo [uB] [501 Capen Hall, Box 601600,

Buffalo, NY 14260-1600; Tel: 716/645-2901] have discovered a molecule

compound

that is effective against Pseudomonas aeruginosa, the gram-negative

infection

that strikes - and usually kills - cystic fibrosis patients and many others

whose immune systems are compromised. That bacteria and many others

routinely

treated by antibiotics have developed antibiotic-resistant strains. The

compound

works by inhibiting the sophisticated communication system used by such

bacteria

called quorum sensing. The work appears in the January 25 issue of Chemistry

&

Biology.

Quorum sensing is the process by which bacterial cells " sense " that their

numbers have reached a certain level, explains UB Associate Professor of

Chemistry Hiroaki Suga. The bacteria do this in preparation for an effective

attack. The process gets switched on, Suga says, in response to the

autoinducers

that accumulate in bacterial cells as they begin reproducing.

Once the cells " sense " that a quorum has been reached, they begin to

communicate, a process that in turn " throws the switch " for manufacturing

virulence factors, such as biofilms. The tough, layered, polysaccharide

shells

provide the bacteria with a nearly impenetrable, self-protective mechanism

that

makes it extremely difficult, and in some cases impossible, to fight with

antibiotics.

" Underneath the protective biofilm, the cells are happily reproducing,

damaging the tissue and producing toxins, " says Suga.

Based on the structure of the quorum-sensing molecule, the autoinducer, the

UB team synthesized a library of compounds. The approach allowed the

scientists

to discover a subset of molecules that, like the natural autoinducer,

activate

quorum sensing. " We then synthesized a small, focused library of

quorum-sensing

agonists, " says Suga. " Surprisingly, this focused library yielded a

quorum-sensing antagonist. It has been shown that knockout of the

quorum-sensing

genes in P. aeruginosa significantly reduced its virulence, so this

cell-to-cell

communication process is an interesting new drug target, " he says.

By disrupting the communication process the new compound could lead to

agents

that will prevent the formation of biofilms, restoring the potency of

antibiotic

treatments and limiting the development of antibiotic resistance. Since many

other bacterial infections operate through quorum sensing, the molecule

likely

will boost research into methods to disrupt those as well.

Compounds that inhibit quorum-sensing work differently from traditional

antibiotics by attenuating pathogenicity, and therefore could prove very

effective against resistant strains. Suga says the quorum-sensing system is

responsible for regulating a number of genes, including those that control

the

production of virulence factors.

" We now have a synthetic molecule that inhibits the master regulatory gene

of

quorum sensing, " he says. While Pseudomonas aeruginosa, which is ubiquitous

in

hospitals, has no effect on healthy people, it can be lethal to patients

whose

immune systems are compromised. In addition to cystic fibrosis patients,

whose

lungs become clogged with the bacteria, it infects patients receiving

chemotherapy, burn patients, AIDS patients, those on ventilators, with

catheters

and others.

" The resistance problem demands development of a new type of drug, which

differs in concept from traditional antibiotics, " Suga says. A patent

application has been filed on the method of synthesis and the compound, he

says.

[Guest guest]

HEADLINE: Molecule Could Prevent Biofilm

Researchers at the University at Buffalo [uB] [501 Capen Hall, Box 601600,

Buffalo, NY 14260-1600; Tel: 716/645-2901] have discovered a molecule

compound

that is effective against Pseudomonas aeruginosa, the gram-negative

infection

that strikes - and usually kills - cystic fibrosis patients and many others

whose immune systems are compromised. That bacteria and many others

routinely

treated by antibiotics have developed antibiotic-resistant strains. The

compound

works by inhibiting the sophisticated communication system used by such

bacteria

called quorum sensing. The work appears in the January 25 issue of Chemistry

&

Biology.

Quorum sensing is the process by which bacterial cells " sense " that their

numbers have reached a certain level, explains UB Associate Professor of

Chemistry Hiroaki Suga. The bacteria do this in preparation for an effective

attack. The process gets switched on, Suga says, in response to the

autoinducers

that accumulate in bacterial cells as they begin reproducing.

Once the cells " sense " that a quorum has been reached, they begin to

communicate, a process that in turn " throws the switch " for manufacturing

virulence factors, such as biofilms. The tough, layered, polysaccharide

shells

provide the bacteria with a nearly impenetrable, self-protective mechanism

that

makes it extremely difficult, and in some cases impossible, to fight with

antibiotics.

" Underneath the protective biofilm, the cells are happily reproducing,

damaging the tissue and producing toxins, " says Suga.

Based on the structure of the quorum-sensing molecule, the autoinducer, the

UB team synthesized a library of compounds. The approach allowed the

scientists

to discover a subset of molecules that, like the natural autoinducer,

activate

quorum sensing. " We then synthesized a small, focused library of

quorum-sensing

agonists, " says Suga. " Surprisingly, this focused library yielded a

quorum-sensing antagonist. It has been shown that knockout of the

quorum-sensing

genes in P. aeruginosa significantly reduced its virulence, so this

cell-to-cell

communication process is an interesting new drug target, " he says.

By disrupting the communication process the new compound could lead to

agents

that will prevent the formation of biofilms, restoring the potency of

antibiotic

treatments and limiting the development of antibiotic resistance. Since many

other bacterial infections operate through quorum sensing, the molecule

likely

will boost research into methods to disrupt those as well.

Compounds that inhibit quorum-sensing work differently from traditional

antibiotics by attenuating pathogenicity, and therefore could prove very

effective against resistant strains. Suga says the quorum-sensing system is

responsible for regulating a number of genes, including those that control

the

production of virulence factors.

" We now have a synthetic molecule that inhibits the master regulatory gene

of

quorum sensing, " he says. While Pseudomonas aeruginosa, which is ubiquitous

in

hospitals, has no effect on healthy people, it can be lethal to patients

whose

immune systems are compromised. In addition to cystic fibrosis patients,

whose

lungs become clogged with the bacteria, it infects patients receiving

chemotherapy, burn patients, AIDS patients, those on ventilators, with

catheters

and others.

" The resistance problem demands development of a new type of drug, which

differs in concept from traditional antibiotics, " Suga says. A patent

application has been filed on the method of synthesis and the compound, he

says.