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Researchers Seek to Counteract Bioengineered Anthrax

Global Security Newswire
By Chris Schneidmiller

WASHINGTON — Researchers from Canada and the United States have developed a drug that could someday be used to treat people exposed to anthrax bacteria specifically engineered to overcome antibiotics (see GSN, July 31).

The “inhibitor” in animal testing prevented anthrax bacteria from using a cellular protein to enter and infect the cell, according to scientists from the Rensselaer Polytechnic Institute in New York and the University of Toronto.

“There is … an increasing concern that therapeutics developed for bioterrorism agents may be rendered ineffective if the microbial target is altered intentionally. This problem could be overcome, however, by designing inhibitors that block host proteins used by the pathogen or its toxins to cause disease,” they wrote in an article published last week in the Proceedings of the National Academy of Sciences.

The main course of treatment today for exposure to anthrax — either in nature or through intentional acts, such as the 2001 U.S. mailings that killed five people — is with antibiotics. Experts interviewed for this article said they had no knowledge of development of a weaponized form of the pathogen designed to overcome antibiotics.

“However, there are many reports demonstrating the development [of] antibiotic resistant strains of anthrax — it’s not difficult to do,” study co-author Jeremy Mogridge of the University of Toronto said by e-mail.

“It’s a matter of isolating bacteria that can grow in the presence of the antibiotic,” he added. “Although most bacteria will die, a very small percentage will naturally have some degree of resistance. It doesn’t require expensive equipment or much expertise.”

Reports have shown isolated incidents in areas such as India in which anthrax strains naturally proved to have some level of resistance to antibiotics, said Phil Baker, anthrax program officer at the National Institute of Allergy and Infectious Diseases.

“They don’t occur very often in nature,” said Baker, whose agency provided $400,000 in funding for the inhibitor project.

Scientists have developed antibiotic-resistant strains of anthrax in order to determine how to overcome such forms of the disease, said Gigi Kwik Gronvall, senior associate at the University of Pittsburgh ’s Center for Biosecurity. The likelihood of terrorists or enemy states producing such a weapon is known only to would-be developers themselves, she said.

The limitations of vaccines and antibiotics in treating anthrax infection highlight the need for additional methods of care, Gronvall said. Patients treated only with antibiotics following onset of advanced sickness are unlikely to survive, while the existing U.S. stockpile of licensed anthrax vaccine for civilians is sufficient to treat only 530 people, according to a November 2005 paper she wrote with center senior associate Luciana Borio.

Rather than seeking to eliminate anthrax bacteria inside the body, as with antibiotics, the U.S. and Canadian researchers since 2002 have sought ways to prevent human cells from becoming infected and spreading the disease throughout the body.

Their inhibitor attaches at multiple points to a receptor — a protein found on most cells — used by the anthrax toxin to enter cells. It then acts as a barrier between the cell and the bacteria. Using more than one point of attachment also increases the level of protection, scientists said.

“The only way to circumvent such an inhibitor would be to engineer the toxin to enter human cells through a different receptor,” Mogridge said. That would be considerably more difficult than altering anthrax against antibiotics, he said.

Researchers developed four inhibitors, and then injected rats with the version that proved most potent in cell cultures. That inhibitor protected all six rats exposed to anthrax. Five of six rats that received no protection died in testing, as did another six treated with an inhibitor that attached only at one point to the cell receptor.

Further development and animal testing is required on the inhibitor, a process that could take several years, according to Mogridge and fellow project lead researcher Ravi Kane of Rennselaer Polytechnic. The inhibitor must be shown to be effective at treating anthrax infection without causing side effects.

The drug could ultimately be used in conjunction with other countermeasures to provide greater protection from inhalational anthrax, which has a 75 percent fatality rate even with use of antibiotics, according to a press release from Rensselaer Polytechnic.

The inhibitor could save lives even if the bacteria are not resistant to antibiotics, or when treatment begins some time after infection, Baker said. Additional countermeasures could also help reduce the risk posed by nonadherence to the full antibiotic regime, which can last for up to 60 days, Gronvall said.

Inhibitors could potentially be developed for other viral diseases, such as influenza, AIDS and SARS, researchers said.

“We don’t have anything like it so this is really a unique and very important finding,” Baker said.