June 1996
WASHINGTON, D.C. — A strain of the bacterium Streptococcus pneumoniae, resistant to the six most frequently used antibiotics and spread worldwide, appears to disguise itself from the immune system by changing its coat, scientists from the Rockefeller University reported.
"We found a strain of multidrug-resistant S. pneumoniae that appears to have taken genes from another strain to switch its coat and evade the immune system," said Alexander Tomasz, PhD, head of the laboratory of microbiology at Rockefeller. "This method of disguise could be a major contributor to the worldwide spread of resistance to antibiotics like penicillin. What we have learned may be useful for designing new anti-pneumococcal vaccines."
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S. pneumoniae is a common source of bacterial infections in children, the elderly and immunocompromised patients, Tomasz said. Scientists estimate that this bacterium is responsible for up to 7 million cases of otitis media in children, and about 500,000 community-acquired pneumonia cases each year in the United States alone.
In a study of S. pneumoniae, Tomasz and Mirjana Nesin, MD, found a multidrug-resistant form of the 23F strain that had switched its outermost coating (the capsule) to that of a S. pneumoniae 14 strain. Nesin is associated with the Perinatology Center at Cornell University Medical Center and is a guest investigator at Rockefeller in Tomasz's laboratory.
Although the bacteria in their study came from one child's throat, the scientists also found evidence of similar capsular switches involving the same 23F multidrug-resistant strain among isolates from people in New York City and from hospitalized patients in South Korea. In these cases, the bacteria appeared to adopt capsules of either the S. pneumoniae 9 or 19 strains, according to Nesin, who spoke here recently at the Pediatric Academic Societies' annual meeting.
Switching capsules is important, Tomasz explained, because it could provide the bacterium with a temporary, protective disguise to hide from antibodies, which are tailored to match the capsule of each pneumococcal strain. Antibodies for one kind of capsule do not attach to another. Immune cells recognize and destroy bacteria tagged with antibodies.
In the study, Tomasz and Nesin examined the molecular structure of genetic material by DNA sequencing and fingerprinting to analyze drug-resistant genes in two pneumococcal isolates recovered from the throat of a child attending a day care center.
One of these isolates, with a type 14 capsule, was susceptible to all antibiotics. The second isolate was the 23F bacterium resistant to six antibiotics: chloramphenicol, erythromycin, penicillin, a third-generation cephalosporin, tetracycline and trimethoprim-sulfamethoxazole. Tomasz and his colleagues first described these bacteria in a 1995 collaborative study with Frederick Henderson, MD, director of the department of pediatrics at the University of North Carolina, Chapel Hill.
After a few weeks, the type 14 pneumococcal bacteria found in the child was resistant to the same antibiotics as the previously identified 23F multidrug-resistant strain.
On closer examination, the scientists discovered that this multidrug-resistant 14 strain shared several characteristics with the resistant 23F strain. Both strains had identical surface proteins that bind to penicillin, the same DNA sequences of penicillin-binding proteins 2X and 2B genes and an identical overall chromosomal pattern.
"Only the capsule differed between the two strains, strongly suggesting the multidrug-resistant strain with the type 14 capsule is, in fact, a disguised version of the 23F multidrug-resistant bacterium. The 23F strain had switched its outermost coating," Nesin said.
The most likely mechanism for the capsule switch, Nesin and Tomasz suggested, is that the multidrug-resistant 23F bacteria took genes from the drug-susceptible 14 strain during their common residence in the child's throat. This gene-stealing process, or transformation, allows one bacterium to surround itself with a new coating with the help of the imported genes.
In related research, Tomasz and his colleagues have used DNA fingerprinting to document the spread of the multidrug-resistant 23F strain over large geographic distances, including several day care centers and hospitals in the United States, Spain, Portugal, Croatia and Korea.
In 1993, the Centers for Disease Control and Prevention reported resistance to penicillin among more than 40% of pneumococcal bacterium identified from throat samples of children in Atlanta younger than 6 years. Similar or even higher rates of these resistant pneumococci were reported from Spain, Hungary, Japan and Korea, Tomasz noted.
For more information, see:
- Nesin M, Tomasz A. Capsular transformation of multidrug resistant Streptococcus pneumoniae - in vivo. Abstract No. 1070, 36th Annual Meeting of the Pediatric Academic Societies in Washington, D.C., May 6-10, 1996.
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