Nav: Home

Bacterial armor could be a new target for antibiotics

July 18, 2018

For over a century, scientists have studied E. coli, one of the bacteria that cause food poisoning, as a model for fighting infections. Such research has led to a variety of antibiotics that penetrate the protective cell walls of bacteria to kill them.

Now, a multi-university study led by Stanford bioengineer KC Huang reveals that E. coli has managed to keep a big secret about its defenses. He and his collaborators report in Nature that scientists had overlooked the astonishing physical strength of the thin outer membrane that clings to E. coli's stout cell wall.

Scientists had long known that many bacteria have outer membranes. But until now researchers thought of it like a layer of shrink wrap that simply made it tougher to get antibiotics into cells. But as the new study shows, the outer membrane physically protects the cell and could be a good target for a new class of antibacterial drugs.

"We've discovered that the outer membrane can act as a suit of armor that is actually stronger than the cell wall," said Huang, an associate professor of bioengineering and of microbiology and immunology. "It's humbling to think that this function had been hiding in plain sight for all these years."

Huang said the findings suggest new infection-fighting strategies for the roughly half of all bacterial species that, like E. coli, have outer membranes. "If we can attack the outer membrane, infectious bacteria will be pre-weakened for targeting with antibiotic treatments that disrupt cells in other ways," he said.

Chemical shields

All bacteria have a cell wall that surrounds and protects the cell's inner workings. Many decades ago, scientists discovered that E. coli and many other bacteria have an additional layer, called an outer membrane, that surrounds their cell walls.

Since its discovery, this outer membrane has been used as a way to classify bacteria into those that do and do not react to a common staining technique, called a Gram stain. Bacteria with outer membranes do not react to the chemical stain are called Gram-negative. Bacteria with naked cell walls react to the stain and are classified as Gram-positive.

Both kinds of bacteria can become infectious and, when this occurs, the presence or absence of an outer membrane can also help determine how responsive they will be to antibiotics. Gram-negative bacteria - which have outer membranes - tend to be more resistant to antibiotics.

"Scientists knew that outer membranes were chemical shields," Huang said. "Thus, it was easy to relegate this third layer to an annoyance when dosing the cell with antibiotics."

Surprising strength

In recent years, however, researchers have had clues that the outer membrane is more important than they'd thought. In one study, Huang's lab removed E. coli's cell wall but left its outer membrane intact. Unsurprisingly, the bacteria lost their cucumber shape and became blobs. But a large fraction of these blobs survived, multiplied and ultimately regenerated new cucumber-shaped E. coli.

Enrique Rojas, a former postdoctoral scholar in Huang's lab and first author on the new paper, said that study was a clue that the outer membrane must play important structural and protective roles.

"We just listened to the data. Science is about data, not dogma," said Rojas, now an assistant professor of biology at New York University.

Over the last four years, working with collaborators from the University of California, San Francisco, and the University of Wisconsin-Madison, the group members tested the outer membrane's structural powers.

They suddenly collapsed the pressure inside the bacteria, but instead of causing the cell wall to massively shrink, as prevailing assumptions would have predicted, they found that the outer membrane was strong enough to almost entirely maintain E. coli's cucumber shape.

In other experiments, they put E. coli cells through two hours of rapid increases and decreases in pressure. E. coli cells normally shrug off these repeated insults and grow as if no changes at all had occurred. However, when the researchers weakened the outer membrane, cells died quickly.

"The presence or absence of a strong outer membrane is the difference between life and death," Huang said.

The experiments identified a handful of components that give the outer membrane its surprising strength. Drugs that destabilize the deceptively thin outer layer could help destroy infectious bacteria, Huang said.

Huang added that the findings are part of an emerging field of study called mechanobiology. Whereas scientists once viewed cells as sacks of chemicals to be studied by chemical means, today a confluence of tools reveal the infinitely complex structural properties that make cells and organs tick.

"It's a very exciting time to be studying biology," Huang said. "We are approaching the point at which our tools and techniques are becoming precise enough to discern, sometimes at almost the atomic level, the physical rules that give rise to life."
-end-


Stanford University

Related Bacteria Articles:

Conducting shell for bacteria
Under anaerobic conditions, certain bacteria can produce electricity. This behavior can be exploited in microbial fuel cells, with a special focus on wastewater treatment schemes.
Controlling bacteria's necessary evil
Until now, scientists have only had a murky understanding of how these relationships arise.
Bacteria take a deadly risk to survive
Bacteria need mutations -- changes in their DNA code -- to survive under difficult circumstances.
How bacteria hunt other bacteria
A bacterial species that hunts other bacteria has attracted interest as a potential antibiotic, but exactly how this predator tracks down its prey has not been clear.
Chlamydia: How bacteria take over control
To survive in human cells, chlamydiae have a lot of tricks in store.
Stress may protect -- at least in bacteria
Antibiotics harm bacteria and stress them. Trimethoprim, an antibiotic, inhibits the growth of the bacterium Escherichia coli and induces a stress response.
'Pulling' bacteria out of blood
Magnets instead of antibiotics could provide a possible new treatment method for blood infection.
New findings detail how beneficial bacteria in the nose suppress pathogenic bacteria
Staphylococcus aureus is a common colonizer of the human body.
Understanding your bacteria
New insight into bacterial cell division could lead to advancements in the fight against harmful bacteria.
Bacteria are individualists
Cells respond differently to lack of nutrients.

Related Bacteria Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Moving Forward
When the life you've built slips out of your grasp, you're often told it's best to move on. But is that true? Instead of forgetting the past, TED speakers describe how we can move forward with it. Guests include writers Nora McInerny and Suleika Jaouad, and human rights advocate Lindy Lou Isonhood.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...