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Understanding KASUMIN Mode of Action Can Help Guide Product Decisions

Date: 12 Mar 2020 | Author: UPL

Tags: KASUMIN Almonds bactericide pome fruit

As a pome fruit, cherry, walnut or almond grower, you know how potentially devastating bacterial diseases can be to your orchard and bottom line.

You also know antibiotics are indispensable for controlling fire blight in apples and pears, bacterial blast in cherries and walnut blight, and for suppressing bacterial canker on cherry trees.

And unfortunately, if you’ve experienced a disease outbreak as a result of streptomycin- or copper-resistant bacteria, you understand how orchard management becomes even more challenging.

For California almond growers, early-spring cold spells during four of the last seven seasons resulted in significant crop losses due to bacterial blast caused by Pseudomonas syringae pv. syringae. But this year, they too will be able to control bacterial blast on almond trees. February of this year, the Environmental Protection Agency and the California Department of Pesticide Regulation approved a Section 18 emergency exemption for KASUMIN® Bactericide.

KASUMIN is already used from coast to coast — including in California — to control bacterial blast and suppress bacterial canker caused by Pseudomonas syringae pv. syringae in cherries. It’s also registered for use in controlling fire blight caused by Erwinia amylovora in pome fruit and walnut blight caused by Xanthomonas campestris pv. juglandis (also known as Xanthomonas arboricola pv. juglandis). KASUMIN is even used to effectively control copper- and streptomycin-resistant strains of these bacteria.

How is that possible?

The answer lies in the active ingredient’s mode of action.

Insights gained into how KASUMIN works

Kasugamycin, the active ingredient in KASUMIN Bactericide, is an aminoglycoside antibiotic that was first isolated from the bacterium Streptomyces kasugaensis during the 1960s. Scientists recognized early on that kasugamycin is active against disease-causing plant bacteria and fungi. But they also realized that kasugamycin has only weak or almost no antibacterial activity against common pathogenic bacteria of people or animals, even though it belongs to the same antibiotic class as streptomycin (and others).

That’s good news for fruit and nut growers.

Since its discovery, kasugamycin has been used to study protein production in bacteria (specifically gram-negative bacteria like Escherichia coli and Pseudomonas spp.), how and where aminoglycoside antibiotics work, and even resistance development. While scientists don’t have all the answers yet, they have made large strides in understanding the genetic mechanisms of antibiotic resistance in plant-associated bacteria. And by understanding how and why resistance develops, horticulturalists and plant pathologists can develop effective strategies for minimizing it in the future.

Life requires protein production

All living organisms must be able to make proteins to survive. That’s as true for bacteria and fungi as it is for plants, animals and people.

Bacteria make proteins using instructions contained within their genetic code (DNA). DNA is first copied to RNA in a process called transcription. That RNA provides the template for protein synthesis, a process known as translation. 

Ribosomes are the cell structures that “translate” the instructions and build new proteins. They have two main parts or “subunits”: a small 30S subunit and a large 50S subunit. (The “S” stands for Svedberg unit, a measure of a particle’s size based on its sedimentation rate during centrifugation.)

The protein-making process starts when three initiation factors (IF-1, IF-2 and IF-3) bind to the small 30S subunit. This allows messenger RNA (mRNA) to bind to the 30S subunit, followed by a modified methionine-transfer RNA (tRNA) unit. IF-3 leaves the 30S subunit, and a 50S subunit joins the complex to form a functional ribosome. The other two initiation factors are then released from the ribosome.

At this point, the 30S subunit “reads” the mRNA, and an elongation factor delivers the matching amino acid-tRNA molecule to the ribosome. A peptide bond forms between the amino acids, transferring methionine to the new amino acid and leaving an “empty” tRNA. The ribosome then moves along the mRNA, the empty tRNA moves to exit the ribosome, and a new amino acid-tRNA molecule is added. This elongation process continues until a stop signal occurs and a release factor, not tRNA, recognizes it. The result is the release of a new protein, followed by separation of the subunits and mRNA.

So, what does protein production have to do with how KASUMIN works?

Everything.

What we now know, including some kasugamycin modes of action

Like streptomycin, kasugamycin interferes with protein production in bacteria. But how they go about disrupting the process is different.

Streptomycin and other aminoglycoside antibiotics cause mRNA to be “misread” and wrongly “proofread” at the site where new amino acids are being joined. Kasugamycin binds with the 30S subunit in such a way that it overlaps key binding sites within the 30S subunit, distorts the mRNA path in the ribosome, and prevents the initiator methionine-tRNA from recognizing the “start” signal. In other words, kasugamycin inhibits protein production, disrupting bacterial reproduction and life cycle.

For kasugamycin to interfere with ribosomes inside the bacteria, it must get through the inner membrane first. Recently, researchers looked into how kasugamycin enters bacterial cells. What they found is that kasugamycin mimics naturally occurring nutrients to trick E. coli into actively bringing the antibiotic inside. And E. coli aren’t the only bacteria to be fooled. Erwinia amylovora, the bacteria responsible for fire blight in apples and pears, also has importer systems that kasugamycin can hijack to enable entry into the bacteria’s interior. These importer systems, however, aren’t involved in the uptake of streptomycin and oxytetracycline.

So much has been learned about how aminoglycoside antibiotics work to control disease-causing bacteria in plants since these compounds were first discovered. Many more questions remain to be answered.

In the meantime, you’ve got weather and disease forecast models to monitor, orchards to scout and trees to treat. For more information on how to incorporate KASUMIN into your integrated disease management program, please contact your local UPL sales representative.


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