Involved in a breakthrough study of streptococci
By analysing increased production of toxins in common bacteria, type A streptococci, scientists are now for the first time able to define accurately the molecular events that can lead to the bacteria causing worldwide epidemics. The study is based on the sequencing of the entire genome of almost 5,000 type A streptococci that have been collected for decades. Karl G. Kristinsson, Professor at the Faculty of medicine, and head of the Department of infectious disease at the University Hospital, and Magnús Gottfreðsson, Professor at the Faculty of Medicine and the head of the Science Department of the hospital took part in the study.
Scientists from Houston Methodist Research Institute, Houston Methodist Hospital; the National Public Health Institute of Finland, and the U.S. National Institute of Allergy and Infectious Diseases along with Kristinsson and Gottfreðsson cooperated on the study and divulge their findings in the prestigious science publication Journal of Clinical Investigation.
According to James M. Musser, the head of the project and the chief of pathology and genetic research at Houston Methodist Research Institute the results showed certain changes in DNA which in turn seem to lead to large epidemics of type A streptococci infections. These discoveries also open the field to developing new pharmaceuticals or preventive measures against the bacteria, and also improved sequencing technology which might be useful in preventing or reducing epidemics.
According to WHO type A streptococci cause over 600 million infections in humans annually. The majority of the patients get a sore throat, which is rarely serious. However, the bacteria can also cause arthritic fever, an important causal factor in heart diseases in children, which can be prevented. Type A streptococci can also cause serious infections, including blood poisoning and necrotizing fasciitis, diseases which carry a high mortality rate.
It has been known for over a century that this infectious bacterium can cause epidemics, but the reasons for this have so far not been discovered. The research group decided to investigate especially type A streptococci, one reason for this being the serious epidemics the bacteria can cause, and also because of the access to large collections of microbes that had been collected for decades. Due to the relatively small genome, full sequencing of thousands of strains was possible in a short time.
The original hypothesis of the scientists was that genetic changes have led to new epidemics. To test this hypothesis thousands of bacterial genomes were sequenced. What was discovered was that changes in DNA sequences that contribute to the formation of two strong toxins, inducing serious infections in humans. The type A streptococci strains involved in epidemics and serious invasive infections exhibited important and significant changes in the control zone of the toxic genes. The control zone controls how these two significant toxic-coding genes are interpreted and the toxic proteins produced.
The consequence of the two genetic changes is a significant increase in the production of two important toxins called streptolysin O og NAD-glycohydrolase. The third change that was discovered causes a variation of one of the toxins, more active than the original, to be formed. All these changes contribute to creating a microbe more dangerous and fit to cause epidemics than its predecessor.
Musser and the research group hope that that the conclusions of the study will enable other researchers to use similar methods in researching other microbes, like Staphylococcus aureus (the most common cause of skin and soft tissue infections) and bacteria that are immune to antibiotics, like og Klebsiella pneumoniae or Escherichia coli.
The scientists contributing to the article in Journal of Clinical Investigation are: Luchang Zhu, Ph.D. (first author), Randall J. Olsen, M.D., Ph.D., Waleed Nasser, Ph.D., and Stephen B. Beres, Ph.D. (Houston Methodist Research Institute); Jaana Vuopio, M.D., Ph.D. (National Institute for Health and Welfare, Turku, Finland and Turku University, Turku, Finland); Karl G. Kristinson, M.D., Ph.D., and Magnús Gottfreðsson, M.D., Ph.D., (Landspítalinn, National University Hospital, Reykjavík and the University of Iceland); and Adeline R. Porter and Frank DeLeo, Ph.D. (US National Institute of Allergy and Infectious Diseases, National Institutes of Health).
The project was funded by the Fondren fund, and Houston Methodist Hospital, Academy of Finland, and the US National Institute of Allergy and Infectious Diseases, National Institutes of Health. The article will appear in the print version of JCI, Journal of Clinical Investigation in September.
