Battle against bacteria
Enzyme targeted as key to development of new antibiotics
John Gregg
Issue date: 11/9/09 Section: News
Andrei Osterman, Ph.D. of the Burnham Institute for Medical Research and colleagues recently have shown a way to slow the growth of infectious antibiotic-resistant bacteria like Staphylococcus (Staph) , which could in turn produce superior antibiotics in the future.
Using available technology to map dozens of microbial genomes, researchers were able to identify specific vulnerabilities in several pathogens. These vulnerabilities are essential enzymes that bacteria must have in order to grow. Scientists hope to one day develop new drugs that would prevent the normal production of these enzymes.
"Our most optimistic expectation is that our work, which at this point is just a proof of concept, will ultimately lead to the development of a new broad spectrum antibiotic, which will take its due place in ranks of our anti-infective agents," Osterman told the Voice.
The studies at Burnham focused on a particular enzyme called nicotinate mononucleotide adenylyltransferase (NadD), which is necessary for production of the coenzyme nicotinamide adenine dinucleotide (NAD).
NAD is found in all living cells, although, the human form differs from that found in bacteria. NAD is needed for bacteria metabolism and, therefore, growth, propagation and survival. By preventing the production of NadD, the supply of NAD is cut off, and bacteria are unable to grow at a normal rate.
"The need for new targets was dictated by the emerging microbial resistance to nearly all existing classes of antibiotics that were historically developed against a very limited set of targets," said Osterman. "Therefore, inhibitors of NadD enzyme, if they could be developed, would become prototypes of novel antibiotics."
The study's follow-up research was partially conducted at the University of Texas Southwestern Medical Center. Using a method called protein crystallography, Osterman's colleagues were able to create a 3-D view of the NadD bacterial enzyme. This will help with future study and is a key point in the process of developing new medicine.
Using available technology to map dozens of microbial genomes, researchers were able to identify specific vulnerabilities in several pathogens. These vulnerabilities are essential enzymes that bacteria must have in order to grow. Scientists hope to one day develop new drugs that would prevent the normal production of these enzymes.
"Our most optimistic expectation is that our work, which at this point is just a proof of concept, will ultimately lead to the development of a new broad spectrum antibiotic, which will take its due place in ranks of our anti-infective agents," Osterman told the Voice.
The studies at Burnham focused on a particular enzyme called nicotinate mononucleotide adenylyltransferase (NadD), which is necessary for production of the coenzyme nicotinamide adenine dinucleotide (NAD).
NAD is found in all living cells, although, the human form differs from that found in bacteria. NAD is needed for bacteria metabolism and, therefore, growth, propagation and survival. By preventing the production of NadD, the supply of NAD is cut off, and bacteria are unable to grow at a normal rate.
"The need for new targets was dictated by the emerging microbial resistance to nearly all existing classes of antibiotics that were historically developed against a very limited set of targets," said Osterman. "Therefore, inhibitors of NadD enzyme, if they could be developed, would become prototypes of novel antibiotics."
The study's follow-up research was partially conducted at the University of Texas Southwestern Medical Center. Using a method called protein crystallography, Osterman's colleagues were able to create a 3-D view of the NadD bacterial enzyme. This will help with future study and is a key point in the process of developing new medicine.