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Researchers identify molecular anchor that allows bacterial invasion of central nervous system

he iagA gene from the Streptococcus inhibited bacterial interactions with the blood-brain barrier, reducing mortality rates up to 90 percent in mice.

"Mice that were infected with the normal, or wild-type, Streptococcus bacteria containing iagA died within days showing evidence of bacterial meningitis. In contrast, most of the mice survived when infected with bacteria missing the single iagA gene," Doran said. "Blocking the anchoring of LTA on the bacterial cell surface could become new a therapeutic target for preventing bacterial meningitis."

Doran and Nizet noted that the study focused on how bacteria can begin the invasion process, and that additional Streptococcus toxins and the body's own immune response also contribute to the development of meningitis. In their ongoing efforts, the researchers are looking at all of these factors in order to paint a complete picture of how the bacteria invade the brain and spinal cord to produce this potentially devastating infection.

Bacterial meningitis must be treated quickly and aggressively with antibiotics, since up to 25 percent of affected children may die or suffer permanent cognitive deficits, cerebral palsy, blindness, deafness or seizures. Therefore, an early acting treatment would help reduce the high rates of disability and death.

"Previous studies have found that Streptococcus bacteria from infants with serious disease have significantly higher levels of LTA than bacterial strains in infants without symptoms," Nizet said. "This underscores the importance of this anchor-LTA interaction, as well as its potential importance as a drug target."

The researchers' work was supported by the Burroughs Wellcome Fund, the American Heart Association, the Edward J. Mallinckrodt, Jr., Foundation, the United Cerebral Palsy Research Foundation and the National Institutes of Health.

Doran and Nizet's colleagues include Erin Engelson, Arya Khosravi and Heather Maisey of UCSD; Iris
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Source:University of California - San Diego


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