Genome Sequencing Study Finds Clues to Determining Causes of Lethal Epidemics

A team of collaborating scientists has sequenced almost 100 full genomes from three successive epidemics of flesh-eating bacteria. This has resulted in the first precise explanation of the biologic events contributing to deadly epidemics of severe infection. This method can be used to track and help prevent epidemics in the future.

The scientists involved in the project were from at the Methodist Hospital Research Institute (Houston, TX, USA), the Broad Institute (Boston, MA, USA), Mount Sinai Hospital (Toronto, ON, Canada) and the Ontario Agency for Health Protection and Promotion (OAHPP). Results of this research, funded by the U.S. National Institutes of Health (Bethesda, MD, USA) and The Methodist Hospital Research Institute, appear in a study published online January 21, 2010, in Proceedings of the [U.S.] National Academy of Sciences (PNAS).

"The extensive full-genome data provide us with new clues about the bacteria's ability to take advantage of vulnerabilities in the person who has contracted the bacteria,” said Dr. James M. Musser, codirector of the Methodist Hospital Research Institute and the senior, corresponding author of the study. "With this type of unique molecular portrait of the bacterial pathogen, we can more effectively develop drugs to prevent the spread of epidemics and construct novel diagnostic and treatment strategies.”

"Until now, it has been a mystery why sometimes we see two opposing types of infection in patients who appear to have the same strain of flesh-eating bacteria,” said Dr. Donald Low, chief microbiologist at Mount Sinai Hospital, medical director of the OAHPP Public Health Laboratories and one of the authors of the study. "In some cases, patients suffer from a devastating infection of tissue and muscle requiring extensive surgery, and, other patients present with a skin infection readily treated with antibiotics. Now, we understand in part why this happens.”

Understanding the full molecular architecture of bacterial epidemics has been a long-sought goal of infectious disease research, Dr. Low noted. Genetics and evolution research has long been hobbled by the lack of comprehensive genome-wide markers. The recent advent of massively parallel DNA sequencing techniques now permits full-genome sequences to be generated quickly. This opens an avenue to answering longstanding but previously economically costly questions in all areas of biomedical research, including bacterial epidemics.

Dr. Musser's lab, working closely with collaborators at Mount Sinai Hospital, the Ontario Provincial Public Health Laboratory, the Broad Institute, and Sequenom (San Diego, CA, USA) utilized short-read-length DNA sequencing combined with mass spectroscopy analysis of single nucleotide polymorphisms (SNPs), to study the molecular pathogenomics of three successive epidemics of invasive infections involving 344 serotype M3 group A Streptococcus in Ontario, Canada.

Sequencing the genome of 95 strains from the three epidemics, coupled with analysis of 280 biallelic SNPs in all 344 strains, revealed an unexpectedly complex population structure composed of a dynamic mixture of unique clonally related complexes. On average, each strain was differentiated from one another by only 49 SNPs and 11 insertion-deletion events (indels) in the core genome.

The investigators revealed that each strain has a distinct genome sequence, which brings unparalleled ability to monitor strain spread. The extensive full-genome data permitted the investigators to identify genes with unusually high rates of genetic variation, thereby providing new insights into selective forces at work in the host.

Related Links:
Methodist Hospital Research Institute
Broad Institute
Mount Sinai Hospital
Ontario Agency for Health Protection and Promotion
Sequenom