‘Big things, Momma, from small things someday come’: Antibiotics, Part II

In the last column we met scientists Joan Strassmann and Pierre Stallforth, and left Joan, lying on the ground in a Virginia forest, peering through a magnifying glass at a pile of steaming deer scat. She saw the first Dictyostelium fruiting body in the wild, sprouting out of a pellet of poop.

We thought that was fun, but a small thing, a curiosity. But something bigger came of it. (The Nitty Gritty Dirt Band is at Mashantucket on Aug. 5). That song could be an anthem of science; progress usually springs from small starts. The origins of microbiology and much of medicine derive from Louis Pasteur’s experiments with crystals of sodium tartrate, followed by step including the germ theory of disease, that built over time.

In the 1960’s some physicians thought they had infection on the run, but they had not reckoned with the uncanny ability of bacteria to mutate to drug resistance. In 1961, I asked a pediatrician friend of my family if he could help me find antibiotics among the molds of Laconia, New Hampshire. Great idea! he said, and we set to work; I planned to exhibit at the high school science fair. I isolated molds and Dr. Baker taught me to spread bacteria on blood agar petri dishes and then put molds next to them. We hoped that secreted fungal products would kill renal E. coli and pathogenic Streptococcus bacteria. None did.

New antibiotics are still a priority, and some of the methods are the same as when Alexander Fleming discovered penicillin in the 1920’s. Find something that grows on a Petri dish and test it against bacteria. This approach has limitations — most microorganisms do not grow on a Petri dishes filled with nutritious agar. Sebastian Götze and his colleagues in Pierre Stallforth’s lab in Germany developed a method to find antibiotic producing genes that avoids these problems.

They call it “ecological niche genome mining.”

They found a group of organisms growing together in what ecologists and evolutionary biologists call a niche. The organisms compete but have produced a stable co-existence that could require production of an antibiotic by one or the other member of the community. The goal is to find the gene that produces that antibiotic. They do not have to grow the organisms on Petri dishes. At this point, scientists (or students) collect the community of cells and dissolve them in a detergent that destroys most molecules but leaves DNA intact. The DNA comes from many species, but no matter. They can be identified by the sequences recovered. Students are valuable in this effort and can quickly end up with enough DNA in a plastic tube to work for a long time. Soon they learn to sequence DNA and analyze it. Finding something useful tends to concentrate their minds.

The Keanumycins (after Keanu Reeves), came from Pseudomonas bacteria living in the fluid of a Dictyostelium fruiting body, descendants of the one Dr. Strassmann found in Virginia. That niche was composed of Dictyostelium amoebae that had transformed into a fruiting body that had a droplet of a few microliters at the top of a stalk. The droplet (our niche) had about 80,000 tough spores. It also has Pseudomonas bacteria called QS1027, that floats outside the spores.

Sometimes a nematode crawls up the stalk and writhes in the droplet of our little community, making it shake. Shaking fruiting bodies with worms in them are a little freaky the first time you see them. Victor Zaydfudim, a high school student in our lab noticed them 20 years ago.

What do the Keanunmycins do? There are three, plus several others that detected earlier. They do not kill bacteria. Rather, they punch holes in cell membranes of amoebae and fungi, which can be dangerous pathogens. Keanumycin A is a complex ring molecule with a two variants.

One amoeba of Dictyostelium can eat 300 pseudomonas bacteria in an hour, but not when the bacteria make keanumycin and or a second drug called jessinipeptin. These are lead natural product compounds for a new class of antibiotics.

Keanumycin A kills Dictyostelium at very low concentration, which is expected from its derivation, but it also kills several pathogenic Acanthamoeba species. The drug resistant yeast strain Candida auris, which can kill humans, is also controlled by keanumycin in vitro. (We are a long way from injecting these drugs).

The most important effects of keanumycin may be in agriculture because it kills Botrytis cinerea and other phytopathogens, Botrytis blight is a serious pest of greenhouse crops and vineyards. Pierre Stallforth and his colleagues are using the Hydrangea plant as their model organism.

Botrytis infects hundreds of plants, so they chose one. I wonder if these or other natural products will help control diseases of our trees.

 

Richard Kessin, Ph.D, is Emeritus Professor of Pathology and Cell Biology in the Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University Irving Medical center. His columns are at RichardKessin.com.

The views expressed here are not necessarily those of The Lakeville Journal and The Journal does not support or oppose candidates for public office.

Latest News

A new life for Barrington Hall

A new life for Barrington Hall

Dan Baker, left, and Daniel Latzman at Barrington Hall in Great Barrington.

Provided

Barrington Hall in Great Barrington has hosted generations of weddings, proms and community gatherings. When Dan Baker and Daniel Latzman took over the venue last summer, they stepped into that history with a plan not just to preserve it, but to reshape how the space serves the community today.

Barrington Hall is designed for gathering, for shared experience, for the simple act of being together. At a time when connection is often filtered through screens and distraction, their vision is grounded in something simple and increasingly rare: real human connection.

Keep ReadingShow less

Gail Rothschild’s threads of time

Gail Rothschild’s threads of time

Gail Rothschild with her painting “Dead Sea Linen III (73 x 58 inches, 2024, acrylic on canvas.

Natalia Zukerman

There is a moment, looking at a painting by Gail Rothschild, when you realize you are not looking at a painting so much as a map of time. Threads become brushstrokes; fragments become fields of color; something once held in the hand becomes something you stand in front of, both still and in a constant process of changing.

“Textiles connect people,” Rothschild said. “Textiles are something that we’re all intimately involved with, but we take it for granted.”

Keep ReadingShow less

Sherman Players celebrate a century of community theater

Sherman Players celebrate a century of community theater

Cast of “Laughter on the 23rd Floor” from left to right. Tara Vega, Steve Zerilli, Bob Cady (Standing) Seated at the table: Andrew Blanchard, Jon Barker, Colin McLoone, Chris Bird, Rebecca Annalise, Adam Battlestein

Provided

For a century, the Sherman Players have turned a former 19th-century church into a stage where neighbors become castmates, volunteers power productions and community is the main attraction. The company marks its 100th season with a lineup that blends classic works, new writing and homegrown talent.

New England has a long history of community theater and its role in strengthening civic life. The Sherman Players remain a vital example, mounting intimate, noncommercial productions that draw on local participation and speak to the current cultural moment.

Keep ReadingShow less
google preferred source

Want more of our stories on Google? Click here to make us a Preferred Source.

Reimagining opera for a new generation

Reimagining opera for a new generation

Stage director Geoffrey Larson signs autographs for some of the kids after a family performance.

Provided

For those curious about opera but unsure where to begin, the Mahaiwe Theater in Great Barrington will offer an accessible entry point with “Once Upon an Opera,” a free, family-friendly program on Sunday, April 12, at 2 p.m. The event is designed for opera newcomers and aficionados alike and will include selections from some of opera’s most beloved works.

Luca Antonucci, artistic coordinator, assistant conductor and chorus master for the Berkshire Opera Festival, said the idea first materialized three years ago.

Keep ReadingShow less
BSO charts future amid leadership transition and financial strain

Aerial view of The Shed at Tanglewood in Lenox, Massachusetts.

Provided

The Boston Symphony Orchestra is outlining its path forward following the announcement that music director Andris Nelsons will step down after the 2027 Tanglewood season, closing a 13-year tenure.

In a letter to supporters, the BSO’s Board of Trustees acknowledged that the news has been difficult for many in its community, while emphasizing gratitude for Nelsons’ leadership and plans to celebrate his final season.

Keep ReadingShow less
A tradition of lamb for Easter and Passover

Roasted lamb

Provided

Preparing lamb for the observance of Easter is a long-standing tradition in many cultures, symbolizing new life and purity. For Christians, Easter marks the end of Lenten fasting, allowing for a celebratory feast. A popular choice is roast lamb, often prepared with rosemary, garlic or lemon. It is traditional to serve mint sauce or mint jelly at the table.

The Hebrew Bible suggests that the last plague God inflicted on the Egyptians, to secure the Israelites’ release from slavery, was to kill the firstborn son in every Egyptian home. To differentiate the Israelites from the Egyptians, God instructed them to mark their doorposts with the blood of a lamb. Today, Jews, Christians and Muslims generally believe that God would have known who was Israelite and who was Egyptian without such a sign, but views of God’s omnipotence in the Abrahamic faiths have evolved over the millennia.

Keep ReadingShow less
google preferred source

Want more of our stories on Google? Click here to make us a Preferred Source.

google preferred source

Want more of our stories on Google? Click here to make us a Preferred Source.