The ability of Streptococcus mutans (S mutans) to survive in acid is one reason that the species is the main driver of tooth decay worldwide. Past research has shown that this ability has several components, including the bacterial enzyme called fatty acid biosynthase M (FabM). When shut down, FabM makes S mutans almost precisely 10,000 times more vulnerable to acid damage. Early work suggests that FabM or one of its relatives may also help all Streptococci (strep) and Staphylococci (staph) infections resist the human body’s defenses, including immune cells that subject bacteria to acid. Between them, strep and staph bacteria are responsible for meningitis, pneumonia, sepsis, methicillin-resistant staph aureus, the “flesh-eating” infection (fasciitis), as well as infections on heart valves and around stents. While FabM represents a major target for the design of new drugs, the focus of the next round of work is to identify and rank every one of the 2,000 known S mutans genes that contributes to its “fitness” (ie, ability to survive, out-compete other strains, and cause disease). A University of Rochester Medical Center research team announced that it has received a $3.6 million fitness-profiling grant from the National Institute of Dental and Craniofacial Research. Grant-funded projects will seek to create a catalogue of proteins that, along with FabM, can serve as targets for a multipronged attack on bacteria that tend to evolve around single-thrust treatments. “Our first goal is to force the major bacterium behind tooth decay to destroy itself with its own acid as soon as it eats sugar,” said principal investigator Robert G. Quivey, PhD, “…could help lead to new antibacterial combination therapies for many infections that have become resistant to antibiotics.” His team has genetically engineered the first and only mutant form of S. mutans with the FabM gene removed, which is a living model that shows the exact impact of the enzyme in live bacteria. Without FabM, the mutant fills its outer membrane with other smaller fatty acids that are much less acid-resistant than those normally created via FabM but that still provide some protection from acid. Thus, a goal is to design a treatment that would prevent S mutans from forming both straight chain and “smaller chain” fatty acids.
(Source: ScienceDaily. Retrieved January 9, 2008, sciencedaily.com/releases/2008/01/080102122300.htm
