C&EN: TODAY'S HEADLINES - BACTERIA BEDECKED WITH KETONES

REBECCA RAWLS

The enzymes that synthesize peptidoglycan, the main component of bacterial cell walls, can be tricked into inserting chemically modified intermediates into these walls, a team of chemists has found. That permissiveness is key to a simple and versatile strategy for displaying compounds on the walls of living bacteria.

Reiko Sadamoto, a research fellow of the Japan Bioindustry Association and Hokkaido University, Sapporo; professor Shin-Ichiro Nishimura of Hokkaido University’s Laboratory of Biomacromolecular Chemistry; and their colleagues performed the studies, expanding a synthetic strategy originated by Chi-Huey Wong and coworkers at Scripps Research Institute [J. Am. Chem. Soc., 124, 9018 (2002)].

The work is “a landmark in cell surface engineering,” says Carolyn R. Bertozzi, professor of chemistry and molecular and cell biology at the University of California, Berkeley. It offers “an elegant approach to metabolic introduction of novel molecular entities into bacterial cell walls.”

The researchers’ paper describes unnatural cell wall components with chemically reactive ketone groups that are subsequently used for conjugation of fluorescence probes, but, in principle, the cell walls could be augmented with any chemical structure. “I envision several possible applications,” Bertozzi says, “including vaccine design and probing how peptidoglycan on living bacteria might interact with effectors of the immune system.”

Earlier work in Bertozzi’s lab and elsewhere used a similar strategy to introduce unnatural molecules onto the surface of mammalian cells through incorporation into sialic acid derivatives displayed on the cell surfaces.

“The current work potentially extends these chemical engineering methods to all types of bacteria, with broad implications for laboratory and biotech applications,” says Kevin J. Yarema, assistant professor of biomedical engineering at Johns Hopkins University. He notes, however, that useful applications remain to be demonstrated.

The researchers are now attempting to use ketones within the cell wall structures to covalently attach antigens to the bacterial cell surface, Nishimura says. If successful, the approach might lead to vaccines based on lactic acid bacteria that could be taken orally. In other experiments, they hope to attach residues to the ketone groups that can later be cross-linked into a sturdy polymer matrix surrounding the bacterium. Such semiartificial bacteria would be very useful in bioengineering production systems, Nishimura suggests.