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Biological Chemistry

Natural Products Offer New Hope For The Honeybee

Antibiotics: Small molecules help explain how a devastating bee-killing bacteria works

by Katharine Sanderson
August 6, 2014

Treatments Needed
Credit: Courtesy of UK Food and Environment Research Agency/Crown © 2014
When American foulbrood takes hold in a honeybee colony (infected comb shown), beekeepers typically must destroy it.
Honey bee combs infected with American foulbrood, a bee colony disease caused by the pathogenic bacterium P. larvae.
Credit: Courtesy of UK Food and Environment Research Agency/Crown © 2014
When American foulbrood takes hold in a honeybee colony (infected comb shown), beekeepers typically must destroy it.

The deadly disease American foulbrood threatens honeybees—and therefore human food supplies—across the globe. But new hope may come from a set of natural products recently discovered by chemists in Germany: The compounds they isolated from the bacterium responsible for American foulbrood give clues about how the disease kills and point to molecular targets for combating it.

American foulbrood, which is caused by the bacterium Paenibacillus larvae, is both deadly and highly contagious. Although a few antibiotics are available to keep the disease in check, if it takes hold, beekeepers have no choice but to burn infected hives. Because pollination by honeybees is critical for cultivating commercial crops from pumpkins to peaches, scientists are hunting for new weapons against P. larvae.

The molecules discovered by independent teams of scientists in Germany may help. Led by Roderich D. Süssmuth at the Technical University of Berlin and Rolf Müller at Helmholtz Centre for Infectious Research at Germany’s Saarland University, the teams found the molecules by taking a close look at clusters of genes from P. larvae. They thought the enzymes encoded by these genes might be responsible for making small molecules that play a role in the bacterium’s deadliness.

Süssmuth’s team looked in particular at the gene cluster encoding a set of nonribosomal peptide synthetase/polyketide synthase enzymes. They painstakingly separated a cultured sample of P. larvae and found a new type of molecule—the paenilamicins—using nuclear magnetic resonance, mass spectrometry, and high-performance liquid chromatography (Angew. Chem. Int. Ed. 2014, DOI: 10.1002/anie.201404572). The paenilamicins have both antibacterial and antifungal properties, they report.

But the paenilamicins don’t kill bees directly. “They are there to outcompete all other” bacteria, Süssmuth says. The team’s experiments showed that paenilamicins kill other bacteria in the bee larvae’s gut, allowing P. larvae to take over.

Computer simulations helped them untangle how the bacterium makes the paenilamicins. Understanding these natural products’ biosynthesis will make it easier to find a way to block their production, or to find an antibody that could stop them from causing so much damage, Müller says.

By looking at other gene clusters in P. larvae, Müller’s group unearthed another class of secondary metabolites, lipopeptide compounds called paenilarvins (ChemBioChem 2014, DOI: 10.1002/cbic.201402139). The three paenilarvins isolated by Müller’s team are antifungal, and Müller hopes studying their mechanism of action will help add to the arsenal of weapons against the bacterium.

“We’d love to see help for the bees,” Müller says, but he admits that there is some way to go. “This work is not the cure, but it’s the prerequisite to find the cure,” he says.

Helge B. Bode of Goethe University in Frankurt says the molecules Müller and Süssmuth isolated are a first step in understanding the deadliness of P. larvae. But many more questions must be answered, says Bode, who was involved in identifying some of the gene clusters in P. larvae’s genome (Appl. Environ. Microbiol. 2014, DOI: 10.1128/aem.04049-13). “The much harder work now is to elucidate the molecular mechanism and how these compounds really act biochemically. What is their molecular target? When is it produced in the bee?”

The small molecules being picked out from P. larvae’s metabolites could help humans in ways other than saving the bees that pollinate our crops—the natural products might be candidates for antibiotic and antifungal drugs. “It’s exciting that natural products are involved in the pathogenesis of such an important bacteria,” Süssmuth says.


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