Scientists uncover break-and-entry strategy of disease-causing bacteria

St. Louis, Jan. 12, 2001 As bacteria become resistant to current antibiotics, scientists are searching for the root causes of infection in order to develop more effective treatments. Researchers at Washington University School of Medicine in St. Louis have come one step closer to understanding how bacteria such as Streptococcus and Staphylococcus operate: These pathogens introduce their toxins by punching holes in the host-cell membrane. The cover of the Jan. 12 issue of Cell features the research. Scientists have made great strides in understanding how Gram-negative bacteria, such as Salmonella and E. coli, infiltrate host cells and establish infection. However, a second class of bacteria called Gram-positive causes human diseases such as strep throat, necrotizing faciitis, toxic shock syndrome and rheumatic fever. "Gram-positive organisms are responsible for five of the top six bacterial infections that are now resistant to multiple antibiotics available today," says study leader Michael G. Caparon, Ph.D., associate professor of molecular microbiology.

The first authors of the study are M.D./Ph.D. student John C. Madden and Natividad Ruiz, Ph.D., now at Princeton University.

Gram-negative bacteria inject previously healthy cells with toxins that disrupt essential processes. Several laboratories have visualized needle-like projections from these bacteria into host cells. Presumably, the projections serve as syringes.

Caparon and colleagues discovered that Gram-positive bacteria use an equivalent technique. Most Gram-positive pathogens contain proteins called cholesterol-dependent cytolysins (CDC). Because these molecules have persisted throughout the evolution of this diverse group, they might play a critical role in infection, the researchers surmised.

Studying the molecular basis of infection has been difficult in the past. But thanks to improved techniques, Caparons group was able to manipulate the bacteria genetically. The researchers made

Contact: Gila Reckess
Washington University School of Medicine

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