OSU team fishing for next generation of antibioltics

Photo courtesy of OSU’s Loesgen Lab ## Researchers Gisela Gonzalez-Montiel and Ross Overacker of Oregon State University process fish and slime swabs collected by marine biologist Misty Paig-Tran of Cal State Fullerton.

Photo courtesy of Fish and Wildlife Research Institute ## The mucus on the surface of fish may be slimy, but it’s a potential gold mine for useful bioactive compounds.

One day in the future, you may take a pill to treat an illness and owe your recovery to tiny microbes flourishing in the slippery layer of mucus that coats fish.

After earning a Ph.D. in chemistry at Georg-August University in Göttingen, Germany, Sandra Loesgen completed post-doctoral fellowships at the Scripps Instituton of Oceanography in La Jolla, California, and National Institutes of Health in Bethesda, Maryland. She is now serving as an assistant professor of chemistry and adjunct professor of pharmaceutical studies at Oregon State University. One of her research specialties is identifying genetically encoded and biologically active microbes with useful pharmaceutical properties.

It is critically important to develop a new generation of antibiotics, as the incidence of bacterial infections resistant to current antibiotics continues to climb. The World Health Organization has warned that this issue will become ever more serious — to the point where a recent study anticipates that drug-resistant infections will affect more people than cancer by 2050.

It may come as a surprise, but more than 70 percent of currently used anti-infectives were derived from naturally occurring chemicals.

Plants and microbes produce a diverse array of complex chemicals, some of which have useful antibiotic, antiviral or cell-toxicity properties. For example, amoxicillin, one of the most commonly prescribed antibiotics, is a derivative of a chemical isolated from Penicillium mold.

Although many previous efforts to identify new anti-infectives have focused on soil microbes, microbes thrive in other media as well.

In fact, they’re found inside us as well as all over us. Animals, including humans, play host to a diverse community of microbes, both within the gastrointestinal system and on the skin.

There’s a growing consensus that these microbes can interact with their host organisms in both positive and negative ways, supporting digestion and reducing pathogenic infections, but also contributing to some types of diseases.

These microbes may also be a source for new antibiotics. For example, researchers recently identified a new antibiotic from a bacterium found in the human nose.

In my lab at Oregon State University, we’ve been working to identify the next generation of antibiotics from the microbes associated with animals. Our current efforts focus on the most diverse group of vertebrates — marine and freshwater fish.

More than 33,000 species of fish species have been identified — more than the sum of all other vertebrates on Earth. These animals often live in challenging environments, and are likely to support microbes that help them resist infections.

We collaborate with marine biologist Misty Paig-Tran of California State University at Fullerton to obtain samples of mucus from a number of different Pacific fish species. Over several trawls, her team was able to collect 17 species of coast-hugging or deep-sea fish. Examples include pink surfperch from coastal waters and midwater eelpouts from deeper waters.

The slimy mucus that coats fishes acts as a protective coating.

As the animal moves through the water, it can come in contact with all kinds of bacteria, fungi, viruses and other types of life. The mucus acts as a physical barrier in warding them off, but researchers speculate there is also a chemical component produced by the fish’s microbiome that assists in the process.

My collaborators and I were looking for interesting bacteria that we could isolate from the surface mucus. Our goal was to explore bioactivity within the bacterial extract in hopes that we could harness it for our own uses.

We are currently exploring the bacteria’s taxonomy — that is, how forms are related and how they should be classified on the tree of life.

Undergraduate researcher Molly Austin and chemistry graduate student Paige Mandelare were able to isolate 47 different bacterial strains from fish mucus swabs. We cultured them, extracted the chemicals they were producing and then tested them to see if they inhibited common human pathogens.

Interestingly, we found that numerous bacterial extracts displayed strong antimicrobial activity. What’s more, 15 exhibited strong inhibition of methicillin-resistant Staphylococcus aureus or MRSA, a drug-resistant human pathogen responsible for many difficult-to-treat infections in humans.

We performed additional testing and analysis on one of the most potent microbial extracts, and found that it was producing multiple analogues of a particular heterocyclic aromatic compound called phenazine that displayed antibiotic activity.

Motivated by these findings, we tested whether compounds in these extracts could also affect cancer cells. We found a Pseudomonas bacterium isolated from a coastal pink surfperch was producing a metabolite that inhibited growth of carcinoma cells in the human colon.

This research is ongoing, in my lab and others.

Whether an effective drug can be derived from an active compound depends on many factors. However, these results suggest microbes associated with fish produce a broad array of diverse and complex chemicals serving as promising fodder for drug discovery efforts.

From The Conversation, an online repository of lay versions of academic research findings found at the conversation.com/us. Used with permission.