Pandorachelins are siderophores: molecules that help bacteria capture, or chelate, the iron they need to survive. But while siderophores may be best known for their iron binding abilities, Leibniz-HKI researchers in Jena have discovered that acquiring iron isn’t all pandorachelins can do. Enzymatic remodeling allows pandorachelins to take on a new role. This transformation may make bacteria better suited for their environments.

“We discovered that certain bacteria can transform a peptide with minor changes into another peptide, changing its function from supporting movement to capturing iron more efficiently. This remarkable transformation shows how bacteria can adapt their molecular tools to meet different needs,” says Elena Herzog, who co-authored the paper as part of her doctoral work alongside postdoctoral researcher Keishi Ishida in the lab of Christian Hertweck, department head at Leibniz-HKI and professor at Friedrich Schiller University Jena.

The search for a missing molecule

Early bioinformatic analysis led researchers to predict that Pandoraea bacteria produce a peptide with a fatty acid. However, upon discovering pandorachelin A, Ishida and Herzog were surprised to note that the fatty acid was nowhere to be found.

The search for this missing fatty acid led them to pandorachelin B, a lipocyclopeptide.

An alphabet where B comes before A

The group’s research unveiled key differences in the structures of pandorachelin A and B. They discovered that pandorachelin B becomes pandorachelin A. This occurs after an acylase, PdnM, cuts off pandorachelin B’s lipid tail, triggering an internal rearrangement that leads to a head-to-tail fusion.

This rearrangement transforms more than just the pandorachelin’s form, however. It also alters function.

• Pandorachelin A is better at binding to iron than pandorachelin B.
• Pandorachelin B’s surfactant properties help bacteria swarm, or move through their environment.

The Hertweck group set out to discover exactly why this transformation occurs.

A sophisticated survival strategy

Pandoraea species are very versatile bacteria that can live under many different conditions and develop resistance to antibiotics. The name Pandoraea references the Greek myth of Pandora’s box, which, when opened, unleashed dangers onto the world. Likewise, some Pandoraea bacteria are opportunistic pathogens which can be especially dangerous for people with compromised immune systems.

In their work, the scientists analysed five Pandoraea species collected from across the globe from lake sediment, two soil samples, root-associated soil in India, and human phlegm.

Here, the researchers found what they described as a ‘sophisticated bacterial strategy’: PdnM activity can alter the ratio of pandorachelin A or B produced to better align with a bacteria’s environment. For example, in the strain from the lake sediment sample, researchers found only pandorachelin A. By contrast, in one strain from a soil sample, both pandorachelin A and B were found. This may be because, in aquatic environments, it is easier for bacteria to swarm, whereas bacteria in non-aquatic environments may need extra swarming support from pandorachelin B. Ultimately, Ishida notes this is an intriguing example of how bacteria can adapt to their environment in order to survive.

What we can learn from bacterial behavior

These new insights into Pandoraea bacteria may also give researchers a better understanding of how to prevent and treat the infections they cause.

“Bacteria are remarkable chemists, and there is still so much we can learn from the way they produce and transform molecules,” Herzog says. “Such insights may ultimately inspire new approaches in various areas ranging from drug delivery to more sustainable chemistry.”

Funding

Funding for this project was provided by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) for CRC ChemBioSys, and the Cluster of Excellence "Balance of the Microverse".