These bacteria may be key to the fight against antibiotic resistance

Summary

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Short Wave Podcast Summary

Episode: These bacteria may be key to the fight against antibiotic resistance

Date: February 9, 2026
Host: Regina Barber (NPR)
Guest: Natalie Balaban, Biophysicist, Hebrew University, Jerusalem

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Overview

This episode dives into the science of antibiotic persistence—a phenomenon distinct from resistance—which could hold the key to countering the growing threat of antibiotic-resistant bacteria. Host Regina Barber and guest Natalie Balaban unpack recent discoveries showing how dormant (persistor) bacteria survive antibiotics and later fuel the evolution of resistance. They discuss a new study from Balaban’s lab, revealing mechanisms behind this dormancy and offering hope for new, more effective drug strategies.

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Key Discussion Points & Insights

1. Origins of Antibiotic Resistance

• Brief History:
  Regina recounts Alexander Fleming’s discovery of penicillin in 1928 and the lifesaving power of antibiotics, followed by the increasing threat of antibiotic resistance.

  “Since then, penicillin and other antibiotics have saved millions of lives with one problem, the growing threat of antibiotic resistance.” (00:22)

2. Defining Resistance vs. Persistence

• Antibiotic Resistance
  Natalie Balaban explains resistance as genetic mutations that let bacteria survive antibiotics:

  “Antibiotic resistance means that somehow the bacterium usually acquired a mutation... it doesn’t do its job and… the bacterium grows happily and it's resistant to penicillin.” (00:56)

• Antibiotic Persistence
  Balaban’s main focus is on persistence:

  • Some bacteria evade antibiotics by entering a dormant, non-growing state.
  • Antibiotics like penicillin target growing, metabolically active bacteria—so dormant ones survive.

  “The penicillin will kill all the growing ones, but the ones that are not growing are going to persist.” (01:54)

3. Clinical Overlook of Persistence

• Most clinicians focus on resistance, but persistence can undermine treatments—especially in immunocompromised patients.

  “In a healthy patient, it's enough for the antibiotic to kill most of the bacteria or even just to arrest the growth. But... in immunocompromised [patients], persistence leads to resistance, and these resistant strains can go and infect other people.” (04:59)

4. Persistence as a Stepping Stone to Resistance

• Balaban’s research confirms that persistence often precedes and enables the evolution of resistance.

  “Persistence. Antibiotic persistence is really a stepping stone for antibiotic resistance... if you are not taking care also of the persistent bacteria, then they will eventually evolve to be resistant to this drug.” (05:59)

5. New Insights into Dormancy: The 'Car Crash' Model

• Historically, dormancy was viewed as an orderly shutdown. Balaban’s new study finds that it can occur through “chaotic” or accidental events—likened to a car crash:

  “You haven't parked your car... you had a car crash and now your car is not moving. This car crash didn't kill them, but it made them stop their growth. And... instead of being bad, turned out to be beneficial because now... they survive the antibiotic treatment." (06:50, 07:41)

  • In infections, contact with immune cells (even if the cell fails to kill the bacterium) can trigger such chaotic dormancy.
  • These bacteria stay dormant, sometimes for days, and may reignite infection once antibiotics are stopped.

  “Their recovery is going to be very, very long... this chaotic bacteria will [eventually] start growing again, and then you'll have a reinfection.” (08:41)

6. Implications for Treatment Strategies

• Dormant bacteria in this disordered state have more permeable membranes. This vulnerability could be a target for new drugs.

  “Their membrane is more permeable... now there are all kind of ideas of how to take advantage of this increased membrane permeability to actually use all kind of compounds that can kill them.” (09:58, 10:15)

• The pathway forward may involve two-step therapies:

  1. Standard antibiotics to kill active bacteria
  2. Membrane-targeting drugs for dormant, chaotic bacteria before ending treatment.

  “Let’s use a compound that is specific against these chaotic bacteria and then stop the treatment.” (11:28)

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Notable Quotes & Memorable Moments

• On persistence feeding resistance:

  “Persistence leads to resistance, and these resistant strains actually can go and infect other people.” —Natalie Balaban (04:59)

• ‘Car crash’ analogy for dormancy:

  “This car crash didn’t kill them, but it made them stop their growth.” —Natalie Balaban (07:41)

• Clinical implications:

  “The chaos that is governing the recovery time of these bacteria is also actually dictating how long the treatment should be.” —Natalie Balaban (09:47)

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Important Timestamps for Key Segments

• 00:22 — Penicillin discovery and intro to resistance
• 00:56 — Defining antibiotic resistance
• 01:54 — Defining antibiotic persistence
• 03:28 — Difference between resistance and persistence
• 04:17 — Dormancy’s role in survival
• 05:59 — Link between persistence and resistance
• 06:50 — The ‘car crash’ dormancy model
• 08:41 — Relevance of dormancy’s chaos for reinfection
• 09:58 — Targeting chaotic persisters
• 11:28 — Two-step strategy for future drug development

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Tone & Style

The conversation is approachable yet precise, blending curiosity with scientific rigor. Balaban uses analogies (“car crash” dormancy) that make complex mechanisms relatable, while Regina prompts with clarifying questions and keeps a tone of accessibility and engagement.

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Summary

This compact episode puts a spotlight on a paradigm shift in fighting antibiotic resistance—namely, by understanding and targeting bacterial persistence in addition to resistance. Natalie Balaban’s research shows that dormant, chaotic bacteria could be the linchpin in both treating persistent infections and slowing the march of resistance. New therapies that exploit their temporary vulnerabilities may redefine the future of antibiotics.

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Transcript

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[Regina Barber]

In 1928, the Scottish physician Alexander Fleming made a discovery that would change the field of medicine forever. He was studying bacteria on agar plates in the lab when he noticed something odd. There weren't any bacteria growing around a spot of mold that had contaminated a part of the plate. It turns out he discovered a medical super compound, penicillin. Since then, penicillin and other antibiotics have saved millions of lives with one problem, the growing threat of antibiotic resistance.

[Natalie Balaban]

Antibiotic resistance means that somehow the bacterium usually acquired a mutation. For example, the penicillin is there, but it doesn't do its job and therefore the bacterium grows happily and it's resistant to penicillin.

[Regina Barber]

This is Natalie Balaban, a biophysicist at the Hebrew University in Jerusalem. And she says more and more bacteria are becoming resistant to all of our antibiotics, which could spell a major problem. One day, all of our antibiotics could stop working unless scientists can find a major weakness in bacteria. Recently, Natalie's lab may have done just that, by hacking dormant bacteria, because antibiotics, they work by killing off growing bacteria, but sometimes bacteria don't grow, they shut down. And in that case, antibiotics, like our guy, penicillin, are rendered useless.

[Natalie Balaban]

The penicillin will kill all the growing ones, but the ones that are not growing are going to persist. And this is what it's called, persistence.

[Regina Barber]

Today on the show, antibiotic Persistence. What it is and how it can help scientists discover new ways to combat a growing bacterial threat. I'm Regina Barber. You're listening to Shortwave, the science podcast from NPR.

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[Regina Barber]

Okay, Natalie, Antibiotic resistance is definitely a problem. We talked about that. But there's another way bacteria evade antibiotics, which is what you study. Right. Like, what is that term?

[Natalie Balaban]

Right. So we study antibiotic persistence, and it's different from resistance because persistor bacteria, they just survive during the antibiotic treatment because they turn onto a dormant form. They just arrest their growth. And when bacteria arrest their growth, then many antibiotics don't work, because antibiotics typically need active growth in order to kill the bacteria.

[Regina Barber]

And then those dormant bacteria can come back once the antibiotic is gone. These are the persisters. So it seems like this dormancy is the key. What did scientists know about this dormant state before you looked into this?

[Natalie Balaban]

So it was known for a long time that when bacteria do not grow, they are not targeted by many antibiotics. They protect themselves from all kind of stresses. So usually when you starve them, they arrest their growth, and then they go into this dormant, protected form. But it was not realized that these dormant forms, once they grow again, they can really lead to the speed up of the evolution of antibiotic resistance.

[Regina Barber]

When we were prepping for this episode, our team learned that clinicians really don't look at persistence in people. They just kind of focus on resistance.

[Natalie Balaban]

So definitely resistance is a major problem. And usually if you have a good immune system and you are given the correct antibiotics, these persistent bacteria, they are there, but your system is the one that is going to take care of them. Okay, so the antibiotics never kill all the bacteria. This we already know. But it's enough. In a healthy patient, it's enough for the antibiotic to kill most of the bacteria or even just to arrest the growth of bacteria. But of course, in immunocompromised versions, or in a part of the body where the immune system doesn't work, or in elderly patients, persistence leads to resistance, and these resistant strains actually can go and infect other people.

[Regina Barber]

Antibiotic persistence can lead to antibiotic resistance?

[Natalie Balaban]

Yes. Actually, we saw that when bacteria are more persistent, they have a higher probability of becoming, at the end of the day, resistant. So in other words, persistence. Antibiotic persistence is really a stepping stone for antibiotic resistance. And it means that any new drug that you put on the market, if you are not taking care also of the persistent bacteria, then they will eventually evolved to be resistant to this drug, and then this drug will not be as effective as it was.

[Regina Barber]

And you published a paper this year in 2026, about how these bacteria can persist in this dormancy state to then become resistant to antibiotics. What did you find in that study.

[Natalie Balaban]

What we found is something that changed the way we look at dormancy. So in the lab we can use for example, these antibiotics that just arrest the bacteria. You can also use all kind of heat stress or ph stress. So there are different stresses and will create bacteria will make them enter a state of gross arrest or dormancy that protects them from different types of antibiotics. Many, many times form it was more, you know, you haven't parked your car and this is why your car is not on the road. It's just, you know, by accident you just, you had a car crash and now your car is not moving.

[Regina Barber]

It's not because you actually stopped because you wanted to.

[Natalie Balaban]

Exactly. This car crash didn't kill them, but it made them stop their growth. And now this crash, instead of being bad for this bacteria, turned out to be beneficial because now the antibiotics comes and they happen to be non growing and therefore they happen to survive the antibiotic treatment.

[Regina Barber]

So what would be like an example of a car crash in this situation?

[Natalie Balaban]

So in the body it can be meeting with an immune cell that is trying to kill the bacteria, but doesn't succeed. Right then would go into this arrest.

[Regina Barber]

They're just putting them in dormant states.

[Natalie Balaban]

They're putting them in dormant state. But what we find out in the lab is that it's not an organized dormant state. It's this car crash type of dormant state.

[Regina Barber]

What does it mean for bacteria to be in this more chaotic dormant state? Like how does that change how they behave or respond?

[Natalie Balaban]

So when they're in this chaotic state, instead of being, you know, these bacteria that when you, when they see an external signal, they, they have a very organized response. Now they are trapped into this state that they didn't plan to enter. And it means that now their recovery is going to be very, very long. Extremely long. In the context of infection, it means that if you had a persistobacteria that was in this chaotic state, now you stop the antibiotics, you may not see anything, but after a day or a few days, this chaotic bacteria will stay, start growing again, and then you'll have a reinfection. So the chaos that is governing the recovery time of these bacteria is also actually dictating how long the treatment should be. Because you know, you need to keep the treatment on for as long as they are in this chaotic state.

[Regina Barber]

Yeah, how could knowing this chaotic, this like dysregulated state like that it exists. How can it help us with future antibiotic treatment?

[Natalie Balaban]

So it really has changed the way we thought about tackling persistobacteria because what we find out in this recent work is that their membrane is more permeable.

[Regina Barber]

Oh, okay.

[Natalie Balaban]

This chaotic state. And now there are all kind of ideas of how to take advantage of this increased membrane permeability to actually use all kind of compounds that can kill them.

[Regina Barber]

How could this like search for these, these new types of drugs change the trajectory of treating antibiotic resistance?

[Natalie Balaban]

So I think it's, it's really realizing that in order to prevent the evolution of resistance, there are many things to do. One of them is to prevent these persisto bacteria from reemerging in these very long infections and preventing from them from re emerging means treating them with these, probably with these membrane targeting compounds before we stop the antibiotic treatment completely. So and then we've treated most of the bacteria. The only ones surviving are these chaotic bacteria. Now let's use a compound that is specific against these chaotic bacteria and then stop the treatment.

[Regina Barber]

Natalie, thank you so much for talking to me about antibiotic persistence.

[Natalie Balaban]

Thank you.

[Regina Barber]

If you like this episode, listen to our shows on extreme bacteria in Yellowstone and the last universal common ancestor. Link to them in our show notes and follow us on the Empire app or wherever else you get your podcasts. This episode was Produced by Burleigh McCoy and edited by our showrunner Rebecca Ramirez. It was fact checked by Tyler Jones. Jimmy Keeley was the audio engineer. I'm Regina Barber. Thank you for listening to shortwave from npr.

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