Mar. 4, 2002 The culprits behind antibiotic-resistant diseases now plaguing hospitals worldwide have been harboring a secret -- one that Rockefeller scientists have recently exposed. It seems these infectious microbes termed Staphylococcus aureus are not independent criminals working alone.
Rather, they are members of only a few massive "superbug" families, which have spread out and conquered the globe.
The findings, reported in the March 1 issue of Lancet Infectious Diseases, suggest that a close examination of what makes these particular pathogens so powerful may allow scientists to locate and target their weaknesses and subsequently develop novel disease-fighting drugs.
"The secrets of the spectacular success of these S. aureus lineages may be hidden in their unique genetic background and may ultimately lead to new strategies to help fight these dangerous microbes," says Alexander Tomasz, Ph.D., head of the Laboratory of Microbiology at The Rockefeller University and second author of the paper.
Scientists at the Laboratory of Microbiology at Rockefeller University and from the Laboratory of Molecular Genetics at the Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa, Portugal, conducted a major study of methicillin-resistant S. aureus (MRSA) - the most important antibiotic-resistant bacterium or "superbug" dominating hospitals worldwide - beginning six to seven years ago.
The study involved collecting a large number of MRSA strains, or clones, from diseased patients in 160 hospitals located in Southern and Eastern Europe, five Latin American countries, the United States and Japan. The collection of strains was from hospitals in which the frequency of disease by drug-resistant MRSA was high. Using DNA fingerprinting techniques, similar to the ones used in forensic medicine and in criminal investigations, the researchers probed the bacterial culprits responsible for hospital-borne MRSA infections.
The findings were astonishing: in more than two thirds of the 3,067 MRSA isolates, the researchers identified the fingerprints of as few as two drug-resistant clones of MRSA. "We kept seeing the same two bugs again and again," says Duarte Oliveira, a visiting scientist and first author of the study.
"It was like finding the same two fingerprints in crimes committed on three continents in Latin America, United States, and Southern and Eastern Europe," says Herminia de Lencastre, senior research associate at Rockefeller and head of the Laboratory of Molecular Genetics at the Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa, Portugal, and senior author of the Lancet Infectious Diseases report.
One of these clones already had a long "criminal record" in hospitals: it was a direct descendent of the very first MRSA strain detected in the United Kingdom in 1961. Members of this family of bacteria have since then spread in a truly pandemic fashion to cause disease in such far away places as Argentina, Brazil, the Czech Republic, Hungary, Portugal and Spain. (See press release at http://www.rockefeller.edu/pubinfo/tomasz080801.nr.html).
The second clone was identified as the cause of MRSA disease among 60 percent of the 258 drug resistant S. aureus isolates collected at 29 health care facilities in Connecticut, New Jersey and Pennsylvania in 1998. The same clone was found in abundance in a hospital in Tokyo, Japan, and represents almost half of all MRSA recovered from 12 New York City hospital patients infected with the bacteria in 1996.
Staphylococcus aureus is the most versatile of human pathogens, readily surviving and proliferating in today’s hostile, antibiotic-laden environment. It causes a wide range of potentially life threatening afflictions, ranging from skin infections to infections of the central nervous system, and is the number one cause of the estimated 2 million hospital-borne infections in the United States each year.
Today, at least half of S. aureus infections in U.S. hospitals are caused by strains resistant to many antibiotics, including penicillin, tetracycline, erythromycin and methicillin. Medical practitioners use the antibiotic vancomycin as a last resort therapy when fighting these MRSA strains.
This work was supported by grants from the National Institutes of Health, Fundação para a Ciencia e Tecnologia (Ministry of Science and Technology) and Fundação Calouste Gulbenkian, Portugal.
John D. Rockefeller founded Rockefeller University in 1901 as The Rockefeller Institute for Medical Research. Rockefeller scientists have made significant achievements, including the discovery that DNA is the carrier of genetic information. The University has ties to 21 Nobel laureates, six of which are on campus. Rockefeller University scientists have received this award for two consecutive years: neurobiologist Paul Greengard, Ph.D., in 2000 and cell biologist Günter Blobel, M.D., Ph.D., in 1999, both in Physiology or Medicine. At present, 33 faculty are elected members of the U.S. National Academy of Sciences. Celebrating its Centennial anniversary in 2001, Rockefeller - the nation’s first biomedical research center - continues to lead the field in both scientific inquiry and the development of tomorrow’s scientists.
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