'Zombie' Bacteria Won't Like This: Scientists Devise Technique to Detect Them

As dangerous as resistant bacteria but less known, using the Hebrew University technique to detect tolerant bacteria may profoundly change the course of treatment.

FILE PHOTO: Colorized scanning electron micrograph image made available by the Centers for Disease Control and Prevention shows a strain of the Escherichia coli bacteria. E. coli
FILE PHOTO: Colorized scanning electron micrograph image made available by the Centers for Disease Control and Prevention shows a strain of the Escherichia coli bacteria. E. coli Janice Carr/AP

Antibiotic-resistant gonorrhea or tuberculosis is more than a terrifying thought, it's a spreading problem. A different problem is antibiotic-tolerant bacteria, which come back to life after the antibiotic course is finished and cause havoc.

No, they're not zombie bacteria – they didn't die. They just stopped metabolizing for awhile.

Resistant bacteria, we know how to find. Tolerant bacteria, we didn't. Now the Hebrew University of Jerusalem has developed a technique to achieve that very thing, described in the journal Biophysical Journal.

Prof. Nathalie Balaban of the university's Racah Institute of Physics helpfully explains the difference between resistant bacteria and tolerant bacteria. It's enormous.

RESISTANT bacteria are like the X-men of the germ world. They are mutants that developed a molecular superpower to fight the antibiotic. A resistant bacterium may be able to expel the molecule from its little cell, eat it, disassemble it – however achieved, the antibiotic is vanquished.

Resistance is specific to the antibiotic, which explains why a bacterium resistant to Antibiotic A will still feel the effects of Antibiotic B. (Unless/until it evolves resistance to that too.)

Point being: our bacteria can thrive, multiply and be fruitful in the presence of the antibiotic, Balaban explains. Also, resistance is genetic: a resistant bacterium will split into two resistant bacteria, and so on.

TOLERANT bacteria are ones that are safe from the antibiotic because, for whatever reason, they happen to be in a state of dormancy when the antibiotic was administered. As the medicine eradicated all their bacterial brethren, they just sat there in suspended animation.

Tolerant bacteria have no active mechanism to overcome the antibiotic. They are not resistant, they just happened to be "asleep." If they "wake" after the antibiotic course is finished, they will go on eating and proliferating and causing disease, if they're pathogenic.

You might assume the antibiotic didn't work, or that the bacteria are resistant, but neither is true. (Of course, a given bug could be both resistant and tolerant. That's life.)

Drug-Resistant Gonorrhea: An Urgent Public Health Issue CDC, YouTube

Clinically, the observation in both resistant and tolerant germs is that the bacteria are still there after the antibiotics course. But the way resistant and tolerant bacteria would be treated is totally different.

Resistant bacteria have to be treated with a different antibiotic. Tolerant bacteria have to be treated with more of the same antibiotic.

Wait a second. If we're infected by bacteria, we have billions of them, if not trillions, in our corpus. Statistically, won't every population of bacteria have tolerant individuals?

Yes, it probably will. "As physicists, we looked at the problem mathematically. Indeed, we can predict that in every population there will be a tiny fraction of tolerant bacteria. As long as that percentage is tiny, our body can handle it," explains Balaban. And adds, "But if there's a strain where the percent of tolerant bacteria is big, then we have a problem."

Waiting them out

So the Hebrew University professor and grad student Asher Brauner came up with what they call "a simple method" to detect tolerant bacteria by measuring the time it takes to kill a bacterial population.  

Their metric is called the "minimum duration for killing 99% of the population" (MDK99).

The protocol involves exposing populations of about 100 bacteria each to different concentrations of antibiotics for different time periods, then testing for survivors.

Using the common intestinal bacteria Escherichia coli and the antibiotic ampicillin, the researchers found tolerance levels ranging from 2 to 23 hours.

Knowing that our disease involves tolerant bacteria rather than resistant ones is good, because then the hospital can determine if we should keep taking the antibiotic – in essence, waiting out the tolerant individuals. Eventually, they will wake up and die.

“A take-home message from this is that it is important to complete a course of antibiotic treatment as prescribed, even after the disappearance of the symptoms,” urges Balaban. “Partial treatment gives tolerance and persistence mutations a selective advantage, and these, in turn, hasten the development of resistance.”