Anthrax, Virulence

ANTHRAX, VIRULENCE *********************** A ProMED-mail post <http://www.promedmail.org> ProMED-mail is a program of the International Society for Infectious Diseases <http://www.isid.org> Date: Fri, 28 Mar 2003 17:43:32 -0500 From: ProMED-mail <promed@promedmail.org> Source: NY Times Online [edited] <http://www.nytimes.com/2003/03/27/international/worldspecial/27ANTH.html> Scientists have discovered why different strains of the bacterium that causes anthrax differ so much in virulence, a finding that in theory could produce more effective vaccines and better tools for distinguishing and tracking the lethal germ. But the finding could also aid the creation of designer varieties of anthrax that are potentially deadlier to humans. Because of that potential danger, a debate occurred over whether the discovery should be kept secret, scientists said. In the end, it was decided that the benefits of publication outweighed the risks. The discovery was made by 6 scientists at Louisiana State University, the Lawrence Livermore National Laboratory, and the United States Army Medical Research Institute of Infectious Diseases, the nation's top center for studying germ defenses. It is published in the current Journal of Clinical Microbiology. The lead author, Dr. Pamala R. Coker, formerly at L.S.U. and now at the Livermore laboratory in California, spearheaded the research for her Ph.D. dissertation. The Livermore laboratory once pioneered nuclear arms but increasingly studies biology and germ defenses. The team's finding centers on the anthrax genome, which consists of a single large chromosome and 2 small circles of DNA, known as plasmids, that carry extra genes. The scientists found that, contrary to common belief, each anthrax bacterium carries not just one set of plasmids but up to 243 copies of the first and up to 32 copies of the second, which is known as pX02. The more copies of this plasmid in a bacterial strain, the more capable it is of causing disease, the scientists said. The [virulence] research was conducted in guinea pigs. The scientists found, for example, that an anthrax strain from Mozambique that possessed just one pX02 plasmid killed 25 percent of the test animals. But a strain from Australia with 32 copies of the plasmid left all the guinea pigs dead. [They] also reported that added factors like subtle features of the bacterium's DNA chromosome appeared to help determine virulence. Thus, the anthrax that killed 5 Americans in the germ attacks of 2001 -- the so-called Ames strain -- was found to possess just 2 copies of pX02. But it nonetheless killed 62 percent of the guinea pigs. The pX02 plasmid carries genes that let the anthrax bacterium fashion an outer protein coat that acts as a defensive shield to thwart the immune system of hosts. The scientists suspect that multiple copies of pX02 thicken that coating, letting the germ escape immune damage and multiply to do extensive harm. Scientists had previously identified 89 types of anthrax as genetically distinct but had failed to discover what determined their wide differences in virulence. The plasmid findings, they said, opened a new window on that question. [While more research needs to be done to verify these observations, and if confirmed they may help in the development of new vaccines - Mod.MHJ] it could also aid investigations of germ attacks. Dr. Coker of the Livermore laboratory said the finding could help forensic scientists track down the country and laboratory from which the weapon arose. That, she said, was possible because the plasmid technique acted as a kind of microscope to reveal finer genetic distinctions among the 89 known varieties of anthrax. [She] conceded that the research in theory could also help a genetic engineer make a more deadly form of anthrax by increasing the number of pX02 plasmids. Dr. Kaplan of the University of Texas, who heads the publication board of the American Society for Microbiology in Washington, said no reviewer or official of the society raised objections to publication of the plasmid paper, even though the White House has urged scientists to screen their work carefully for possible harm to national security. Steve Wampler, a spokesman at the California laboratory, said the plasmid research was done before Dr. Coker came to Livermore, but the laboratory nonetheless put the paper through a careful security review. "In the end," he said, "it was decided that it was fine to publish." In addition to Dr. Coker of Livermore and Dr. Hugh-Jones of L.S.U., the paper's authors are Dr. Kimothy L. Smith of the Livermore aboratory, Patricia F. Fellows of the Army research institute, and Dr. Galena Rybachuck and Dr. Konstantin G. Kousoulas of L.S.U. [Byline: William J. Broad] -- ProMED-mail <promed@promedmail.org> [Dr. Coker had raised the point of multiple copies of the _B. anthracis_ plasmids some 3 years ago and then worked to develop the necessary QPCR techniques to see whether she was right. The article is entitled "Bacillus anthracis Virulence in Guinea Pigs Vaccinated with Anthrax Vaccine Adsorbed Is Linked to Plasmid Quantities and Clonality" J. Clin. Microbiol. 2003 41: 1212-1218 and has the necessary methodological details. Thanks to Pat Fellows we were able to use her USAMRIID data from a previous virulence study without killing any more animals and without the delay and costs involved. From one isolate to another, the virulence of this pathogen varies widely, and hopefully this paper injects some reason into that variance. The major objections have centered on the perceived excessive intracellular bulk of multiple plasmid copies. It is now up to our critics to prove us wrong. If it is confirmed, as I firmly believe it will be, it will produce an immediate boost on studies to understand the chromosomal contributions to virulence besides grossly simplifying virulence measurements in the field; up until now virulence studies have concentrated on the pX01 plasmid and the actions of protective antigen (PA), edema factor (EF) and lethal factor (LF). There was a lot of discussion internally and externally on publication, but we held that the future benefits of this research outweighed the possible costs. - Mod.MHJ] ......................................dk/mhj/pg/mpp *##########################################################* ProMED-mail makes every effort to verify the reports that are posted, but the accuracy and completeness of the information, and of any statements or opinions based thereon, are not guaranteed. The reader assumes all risks in using information posted or archived by ProMED-mail. ISID and its associated service providers shall not be held responsible for errors or omissions or held liable for any damages incurred as a result of use or reliance upon posted or archived material. ************************************************************ Visit ProMED-mail's web site at <http://www.promedmail.org>. Send all items for posting to: promed@promedmail.org (NOT to an individual moderator). 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