Viral proteins may prevent bacterial infections

Researchers from Rockefeller University are enlisting proteins produced by viruses in a novel strategy that may someday help prevent bacterial infections in hospitals and nursing homes.

Bacterial viruses, or bacteriophage, worm their way into bacterial cells, copy themselves and then, as an exit strategy, produce enzymes that quickly destroy the bacterial cell wall, killing the bacteria and releasing the viral offspring.

“These are highly evolved enzymes that work efficiently and rapidly to kill specific bacteria. The best use of these enzymes is to decolonize humans from carrying pathogenic bacteria in certain settings, such as hospitals, nursing homes and day care centers,” says Vincent Fischetti, who is presenting data today at the American Society for Microbiology’s Conference on the New Phage Biology.

Bacteria such as group A streptococci, Streptococcus pneumoniae and Staphylococcus aureus are common causes of infections, ranging from minor skin infections and ear infections in day care centers to deadly pneumonia in nursing homes and hospitals. In most instances human beings are the only reservoir of these bacteria, often carrying them unknowingly in their nose or throat. Enzymes targeting these bacteria could be delivered orally or nasally to reduce or eliminate colonization.

“If you greatly reduce the number of bacteria that are carried by individuals in these settings, the chance of infection will be minimized or even eliminated,” says Fischetti.

In animal model experiments, Fischetti and his colleagues colonized mice with streptococcal or pneumococcal bacteria, either orally or nasally. They were able to remove the colonization completely using phage enzymes delivered in a single dose.

Because these enzymes are derived from viruses that infect and kill specific bacteria, they are like smart bombs that target and kill only the species or strain of bacteria for which they were designed. They will not harm human cells or the beneficial microorganisms that live in the nasal passages and throat and help protect against other infections.

The strength and specificity of these enzymes also makes them good candidates for treating infections as well. As they are larger molecules than antibiotics, Fischetti is unsure whether they can reach everywhere in the body that antibiotics do.

“Until we do more animal studies we don’t know how these enzymes will be distributed throughout the body,” says Fischetti. “We do know that if given intravenously they can kill organisms in the blood.”

Fischetti and his colleagues have identified a lytic enzyme from a virus that infects Bacillus anthracis, the bacterium that causes anthrax and are currently testing it in animals as an adjunct therapy against the disease. The hope is that the enzyme will eliminate enough bacteria from the blood after anthrax exposure to extend the window of time during which antibiotic therapy will be effective.