From start to finish, the predatory cycle took about three to
The predator’s speed may be what gave it the edge over the
infection, Mostowy says. B. bacteriovorus attacks fast, chipping
away at the pathogens until the infection is reduced to a level
that the immune system can handle. “Otherwise there are too
many bacteria and the immune system would be overwhelmed,”
he says. “We’re putting a shocking amount of Shigella, 50,000
bacteria, into the fish.”
Within 48 hours, S. flexneri levels dropped 98 percent in the
surviving fish, from 50,000 to 1,000.
The immune cells also cleared nearly all the B. bacteriovorus
predators from the fish. The predators had enough time to
attack the infection before being targeted by the immune system themselves, creating an ideal treatment window. Even if
the host’s immune system hadn’t attacked the predators, once
the bacteria are gone, Willis says, the predators are out of food.
Unable to replicate, they eventually die off.
A clean sweep
Predatory bacteria are efficient in more ways than one. They’re
not just good killers — they eliminate the evidence too.
Typical antibiotic treatments don’t target a bacterium’s DNA,
so they are likely to leave pieces of the bacterial body behind.
That’s like killing a few bandits, but leaving their weapons so
the next invaders can easily arm themselves for a new attack.
This could be one way that multidrug resistance evolves,
Mitchell says. For example, penicillin will kill all bacteria that
aren’t resistant to the drug. The surviving bacteria can swim
through the aftermath of the antibiotic attack and grab genes
from their fallen comrades to incorporate into their own
genomes. The destroyed bacteria may have had a resistance
gene to a different antibiotic, say, vancomycin. Now you have
bacteria that are resistant to both penicillin and vancomycin.
Predatory bacteria, on the other hand, “decimate the
genome” of their prey, Mitchell says. They don’t just kill the
bandit, they melt down all the DNA weapons so no pathogens
can use them. In one experiment that has yet to be published,
B. bacteriovorus almost completely ate up the genetic material of a bacterial colony within two hours — showing itself as
a fast-acting predator that could prevent bacterial genes from
falling into the wrong hands.
On top of that, even if pathogenic bacteria mutate, a common way they pick up new forms of resistance, they aren’t
protected from predation. Resistance to predation hasn’t
been reported in lab experiments since B. bacteriovorus
was discovered in 1962, Mitchell says. Researchers don’t think
there’s a single pathway or gene in a prey bacterium that the
predator targets. Instead, B. bacteriovorus seem to use sheer
force to break in. “It’s kind of like cracking an egg with a
hammer,” Kadouri says. That’s not exactly something bacteria
can mutate to protect themselves against.
Some bacteria manage to band together and cover them-
selves with a kind of built-in biological shield, which offers
protection against antibiotics. But for predatory bacteria, the
shield is more of a welcome mat.
Going after the gram-positives
When bacteria cluster together on a surface, whether in your
body, on a countertop or on a medical instrument, they can
form a biofilm. The thick, slimy shield helps microbes withstand antibiotic attacks because the drugs have difficulty
penetrating the slime. Antibiotics usually act on fast-growing
bacteria, but within a biofilm, bacteria are sluggish and dormant, making antibiotics less effective, Kadouri says.
But to predatory bacteria, a biofilm is like Jell-O — a tasty
snack that’s easy to swallow. Once inside, B. bacteriovorus
spreads like wildfire because its prey are now huddled together
as confined targets. “It’s like putting zebras and a lion in a
restaurant and closing the door and seeing what happens,”
Kadouri says. For the zebras, “it can’t end well.”
Kadouri’s lab has shown repeatedly that predatory bacte-
ria effectively eat away biofilms that protect gram-negative
bacteria, and are in fact more efficient at killing bacteria within
Gram-positive bacteria cloak themselves in biofilms too. In
2014 in Scientific Reports, Mitchell and his team reported finding a way to use Bdellovibrio to weaken gram-positive bacteria,
turning their protective shield against them and perhaps helping antibiotics do their job.
The discovery comes from studies of one naturally occurring B. bacteriovorus mutant with extra-scary spit. The
mutant isn’t predatory. Instead of eating a prey’s DNA to make
its own, it can grow and replicate like a normal bacterial colony. As it grows, it produces especially destructive enzymes.
Zebrafish cleanup Left unchecked, injected Shigella flexneri
bacteria (green) quickly spread through a zebrafish’s hindbrain (top). In
fish treated with Bdellovibrio (red) within 90 minutes of the S. flexneri
injection, the bulk of the infectious bacteria was gone within 18 hours
(bottom, far right).
Shigella plus saline
Shigella plus Bdellovibrio