Researchers identify molecular anchor in CNS infection
anchor, which allows the access of bacteria into the central
nervous system. By blocking the molecules anchoring ability, its
potential importance as a drug target may hold the key to treating
many types of bacterial meningitis.
Meningitis is a major cause of childhood death and disability and findings from this latest discovery could stop Streptococcus, the bacteria which cause meningitis, from penetrating the normally impermeable blood-brain barrier in order to enter the central nervous system.
Scientists from the University of California, San Diego (UCSD) School of Medicine identified and isolated a gene that produces a fat-sugar complex, which in turn anchors a molecule called lipoteichoic acid (LTA) found on the bacterial cell wall.
This anchoring is a necessary first step for bacteria to cross from the bloodstream, through the blood brain barrier into the central nervous system
However, Kelly Doran, assistant professor of paediatrics and Victor Nizet, associate professor of paediatrics admitted: "How this happens is not well known for bacteria. We wanted to see how bacteria interact with blood-brain barrier cells to begin the process of crossing over into the nervous system."
The research involved generating and screening thousands of Streptococcus mutants in a laboratory model of the human blood-brain barrier. Here, the researchers found that a gene called iagA (invasion association gene-A) established a link that allows bacteria to begin making its way into the nervous system by producing a fat-sugar complex that anchors LTA.
By removing the iagA gene from the Streptococcus inhibiton by bacterial interactions with the blood-brain barrier, reduced mortality rates by up to 90 per cent 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," she added.
Bacterial meningitis must be treated quickly and aggressively with antibiotics, since up to 25 per cent 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," he added.
