Researchers report today the genetic comparison of two important isolates of the anthrax bacterium: the well-known Ames strain and an isolate from the recent Florida anthrax attacks. Although the study does not pinpoint the exact origin of the Florida isolate, it confirms previous scientific reports that the bacterium is derived from the Ames strain. In addition, the study shows how whole-genome sequencing technology and computational methods can be a powerful approach for analyzing anthrax and other bacterial outbreaks. Those techniques will enable researchers to more accurately trace the origin of individual bacterial strains, determine if those strains have been genetically modified, and assess differences in their ability to cause disease or resist antibiotics. The report appears online May 9 in Science Express.
"This study provides a framework for future research on the genetic variation among anthrax bacterial strains," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID). NIAID teamed with the Office of Naval Research (ONR), the National Science Foundation, and other agencies to fund the research. "We now can expand on this information by generating genomic sequences for many different anthrax strains, allowing us to distinguish among them at the single-nucleotide level."
Nucleotides are the building blocks of DNA, typically described as the single-letter bases A, C, G and T. The order or sequence of those nucleotides determines the products encoded by individual genes. To learn the complete nucleotide order for the anthrax bacterium, Bacillus anthracis, in 1999 NIAID and other government agencies provided funding to The Institute for Genomic Research (TIGR) in Rockville, Md., to sequence the Ames strain. That strain, contrary to its name, was isolated from a Texas cow in 1981 and has been a staple of anthrax research in many laboratories. In the recent study, scientists from TIGR and Northern Arizona University compared the information gained from the Ames sequence with the whole genome sequence of the Florida anthrax isolate.
Led by TIGR's Timothy Read, Ph.D., Steven Salzberg, Ph.D., and Claire Fraser, Ph.D., the researchers determined many areas of genetic variability between the two bacteria. By screening other known anthrax isolates for differences in those regions, the investigators confirmed previous reports that the Florida B. anthracis isolate was derived from the Ames strain and narrowed down its origins to a defined Ames lineage. In addition to the original 1981 strain, only one other Ames isolate has been reported, from a Texas goat in 1997. By analyzing the newly discovered regions of B. anthracis DNA variability, the researchers determined the Florida strain is derived from the original isolate, not the 1997 goat strain. Their study also suggests the Florida strain had not been genetically modified.
The study does not pinpoint the exact origin of the Florida strain, however, and does not reveal great differences between the original Ames isolate and the bacteria obtained from the Florida attacks. Therefore, although the paper shows that whole-genome sequencing can distinguish between two related isolates, it does not provide a broad set of genetic markers for analyzing different anthrax strains in nature. That was expected, according to Dr. Read, because the two bacteria studied are of the same strain. "It's like taking two first cousins from a remote village, determining their differences, and then trying to differentiate the whole human race based on those differences," he explains. To fully describe B. anthracis in nature, he continues, researchers need to examine more distantly related strains to collect the full component of genetic differences.
To accomplish that task, NIAID has provided additional funding to TIGR, in collaboration with Northern Arizona University, for an expanded, comprehensive genomic analysis of at least 14 B. anthracis strains and closely related bacteria. TIGR will sequence select bacteria to provide a database of genomic information that can be used to distinguish among different strains and to monitor any changes that may appear in the bacterial genome. The database will also help researchers learn more about the genetic variability that causes differences in the biological properties of individual strains.
NIAID's B. anthracis sequencing efforts have developed from the Institute's longstanding commitment to microbial genomics, a commitment that has expanded along with a renewed focus on biodefense. Genomic analysis is a cornerstone of NIAID's recently published biodefense research agenda, and scientists have already begun deciphering the genetic blueprints of the microbes that cause such potential bioterror threats as plague, brucellosis, and epidemic typhus. In late 2001, NIAID established the Pathogen Functional Genomics Research Center at TIGR to serve as an information and reagent resource for scientists studying microbial genomics.
The wealth of information obtained from genomic studies will provide a framework for identifying novel and specific targets for new drugs or vaccines to battle infections from both naturally occurring microbes and potential biological attacks. Genome sequences will also lead to highly specific methods for quickly detecting and identifying different pathogens, a critical need for defense against bioterrorism.
NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
Reference: TD Read et al. Comparative genome sequencing for discovery of novel polymorphisms in Bacillus anthracis. Science Express online, May 9, 2002.
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