EMBARGOED UNTIL 4 P.M. (CST), JANUARY 27, 2000
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Newly discovered "death signal" could hold key to eradicating deadly bacteria
Finding could pave way for novel therapies for pneumococcal disease
(MEMPHIS, Tenn. - January 28, 2000) - Scientists at St. Jude Children's Research Hospital have discovered a death signal that brings about the death of Streptococcus pneumoniae (also known as pneumococcus) - a discovery that could lead to revolutionary new treatments for the killer bacteria.
Pneumococcal disease causes 40,000 deaths in the United States each year and is the leading killer of young children, causing ear infections, sepsis, bacteremia, pneumonia and meningitis. At present, there is no effective pneumococcal vaccine for children younger than 2, who are at higher risk for the disease.
The findings of the team led by Elaine Tuomanen, M.D., Chair, St. Jude Department of Infectious Diseases, are published in the January issue of the journal Molecular Cell. The group has identified a peptide, a group of amino acids, that coordinates cellular functions, which sends a signal to a "death pathway" called VncS-VncR. Once this signalling pathway is activated, the pneumococcus is then destroyed.
Antibiotics and other therapies could be targeted to stimulate this "death pathway," Tuomanen said. The VncS-VncR pathway was discovered in 1999 by the St. Jude team. However, some pneumococci have emerged in nature with the ability to block this pathway. These new threats that can't be killed by conventional antibiotics are "antibiotic tolerant."
One of the elements that makes pneumococcal disease difficult to treat is the fact that, at present, there is no laboratory test to determine if pneumococcal bacteria strains are likely to be antibiotic-tolerant. This discovery will help St. Jude scientists as they work with researchers from other institutions to develop a test that can predict tolerant bacteria. Tolerance occurs when bacteria stop growing in the presence of antibiotics, but do not die. When the antibiotic is removed, the bacteria can grow again. The team has shown that tolerance is often a precursor to all-out antibiotic resistance.
The St. Jude discovery sheds more light in the important search for clues about why bacteria die and the mechanisms that bring about death. Bacteria-killing antibiotics such as penicillins, cephalosporins and glycopeptides bind to their bacterial targets. This event stops bacteria from growing but does not directly kill them. A second process arising from the bacteria itself is necessary to trigger suicidal enzymes that dissolve cell walls. The newly discovered peptide, Pep27, and death pathway are an integral part of this process, Tuomanen said.
"It's always been a puzzle. How does a community of bacteria in a human not just grow beyond control?" Tuomanen said.
Death signals such as Pep27 could explain why that happens; they could help set the "boundaries" of communities of bacteria. The key to stopping bacterial infections is to determine what causes certain bacteria to grow out of control.
"What we're getting closer and closer to doing is putting the pneumococcus in a box and it's not going to be able to get out of it," Tuomanen said. "Once we define the box, then we can understand why some bacteria escape and specifically direct the therapy at how bacteria get out of the box."
St. Jude Children's Research Hospital, in Memphis, Tennessee, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for the catastrophic diseases of childhood. The hospital's work is supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC). All St. Jude patients are treated regardless of their family's ability to pay. ALSAC covers all costs of treatment beyond those reimbursed by third party insurers, and total costs for families who have no insurance.
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