By Sean Henahan, Access Excellence

WASHINGTON, DC (May 10, 1996)- The discovery of a multidrug-resistant form of the Streptococcus bacterium that switches its coat to evade detection by the immune system could prove useful in the design of anti-strep vaccines, reported researchers from Rockefellar University at the annual meeting of the Pediatric Academic Societies.

Photo: EM of Streptococci

"We found a strain of multidrug-resistant Streptococcus pneumoniae that appears to have taken genes from another strain to switch its coat and evade the immune system," says Alexander Tomasz, Ph.D., 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 antipneumococcal vaccines."

The researchers found a multidrug-resistant form of the 23F strain of Strep. that had switched its outermost coating, the capsule, to that of a S. pneumoniae 14 strain. While 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 hospital patients in South Korea. In these cases, the bacteria appeared to adopt capsules of either the S. pneumoniae 9 or 19 strains.

Switching capsules is important, Tomasz explains, because it could provide the bacterium with a temporary, protective disguise to hide from antibodies, the infection-fighting proteins made by the immune system. Antibodies are tailored to precisely match the capsule of each pneumococcal strain, so antibodies for one kind of capsule do not attach to another. Immune cells recognize and destroy bacteria tagged with antibodies.

The researchers used DNA sequencing and fingerprinting to analyze drug-resistant genes in two pneumococcal isolates recovered from the throat of a child attending a U.S. 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 : chloromphenicol, erythromycin, penicillin, third-generation cephalosporin, tetracycline and sulfa-trimethoxazole.

After a few weeks, the scientists found in the same child 'type 14' pneumococcal bacteria 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 (PBP), the same DNA sequences of PBP 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. This indicates the 23F strain had indeed switched its outermost coating.

The most likely mechanism for the capsule switch 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 is also known as transformation. With the help of the imported genes, the 23F bacteria then surrounded themselves with new coatings.

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 U.S. Centers for Disease Control and Prevention (CDC) reported resistance to penicillin among more than 40 percent of pneumococcal bacterium identified from throat samples of children in Atlanta younger than six years. Similar or even higher rates of these resistant pneumococci were reported from Spain, Hungary, Japan and Korea, Tomasz notes.

BACKGROUND

Scientists estimate this bacterium is responsible for up to 6 to 7 million middle ear infections in children, and about a half million cases of community-acquired pneumonia each year in the United States alone. Worldwide, the number of deaths from infections with this bacteria each year are similar to that of tuberculosis--3 to 4 million.

Related information on the Internet

The Biology of Bacterial Drug Resistance

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