Nature Biotechnology pp 702 - 706

A bacterium found in many dairy products has been altered to fight against dental caries. The July issue of Nature Biotechnology reports a study in which beneficial bacterium Lactobacillus zeae is engineered to produce an antibody on its surface that neutralizes the detrimental streptococcal bacteria that cause tooth decay. As this beneficial Lactobacillus bacterium is regarded as safe for use in humans, the new approach seems promising for use in dental treatments to protect against dental caries.

A collaboration of European scientists led by Swedish researcher Lennart Hammarström set out to see whether Lactobacillus could be engineered to both produce an antibody that was efficacious against a pathogen that causes tooth decay and effective over long periods of time. When they administered the engineered Lactobacillus to rats that had been infected with the decay-causing pathogen Streptococcus mutans, they found that the beneficial bacterium reduced not only the number of pathogenic bacteria, but also the number of cavities they produced. In contrast to antibody given alone, which is quickly broken down and/or removed from the mouth, the Lactobacillus was able to persist in the mouth for three weeks, continually fighting the bacteria that cause cavities.

Nature Biotechnology pp 717 - 722 and pp 671 - 672

A screen for finding drugs capable of disrupting protein-protein interactions may prove extremely useful tool in drug discovery. ProteThe new screening system, described in the July issue of Nature Biotechnology, employs protein-dependent RNA catalysts (ribozymes) that can monitor protein-protein, protein-RNA, and protein-small molecule interactions in real time using changes in fluorescence as a readout.

Michael Famulok and colleagues have engineered their ribozymes with fluorescent tags and nucleic acid-protein binding domains. Binding of a protein target to the reporter ribozyme alters the ribozyme’s self-cleavage activity, which can be monitored by changes in the amount of fluorescence detected. The researchers present two applications of the system. In one case, they attach the Rev-binding element (RBE) of human immunodeficiency virus-1 (HIV-1) to a ribozyme and screen a library of antibiotics for small-molecule inhibitors of the interaction between HIV-1 Rev protein and RBE by monitoring fluorescence changes. They identify an inhibitor that subsequently reduced HIV-1 replication in cells. By slightly altering the format, they were also able to monitor interactions between the blood-clotting factor thrombin and its protein partners. The system should be applicable to analyzing interactions of a wide variety of targets, and to screening for inhibitors of these interactions.