forces its way through the outer membrane and seems to seal
the hole behind it. Once within the space between the outer and
inner membranes, the predator secretes enzymes — as damaging
as the movie aliens’ acid spit — that chew its prey’s nutrients and
DNA into bite-sized pieces.
B. bacteriovorus then uses the broken-down genetic building
blocks to make its own DNA and begin replicating. The invader
and its progeny eventually emerge from the shell of the prey in
a way reminiscent of a cinematic chest-bursting scene.
“It’s a very efficient killing machine,” Kadouri says. That’s
good news because many of the most dangerous pathogens
that are resistant to antibiotics are gram-negative (SN: 6/10/17,
p. 8), according to a list released by the WHO in February.
It’s the predator’s hunger for the bad-guy bacteria, the ones
that current drugs have become useless against, that Kadouri
and other researchers hope to harness.
Pitting predatory against pathogenic bacteria sounds risky.
But, from what researchers can tell, these killer bacteria
appear safe. “We know that [B. bacteriovorus] doesn’t target
mammalian cells,” Kadouri says.
Saving the see-through fish
To find out whether enlisting predatory
bacteria might be crazy good and not just
plain crazy, Kadouri’s lab group tested
B. bacteriovorus’ killing ability against
an array of bacteria in lab dishes in 2010.
The microbe significantly reduced levels
of 68 of the 83 bacteria tested.
Since then, Kadouri and others have
looked at the predator’s ability to devour
dangerous pathogens in animals. In rats
and chickens, B. bacteriovorus reduced
the number of bad bacteria. But the animals were always given nonlethal doses
of pathogens, leaving open the question
of whether the predator could save the
Sockett needed to see evidence of sur-
vival improvement. “If we’re going to
have Bdellovibrio as a medicine, we have
to cure something,” she says. “We can
count changes in numbers of bacteria,
but if that doesn’t change the outcome
of the infection — change the number of
[animals] that die — it’s not worth it.”
So she teamed up with cell biolo-
gist Serge Mostowy of Imperial College
London for a study in zebrafish. The aim
was to see how many animals preda-
tory bacteria could save from a deadly
infection. The team also tested how the
host’s immune system interacted with
The researchers gave zebrafish larvae fatal doses of an antibiotic-resistant strain of Shigella flexneri, which causes dysentery in humans. Before infecting the fish, the researchers
divided them into four groups. Two groups had their immune
systems altered to produce fewer macrophages, the white blood
cells that attack pathogens. Immune systems in the other two
groups remained intact. B. bacteriovorus
was injected into an unchanged group and
a macrophage-deficient group, while two
groups received no treatment.
All of the untreated fish with fewer
macrophages died within 72 hours of
receiving S. flexneri, the researchers
reported in December in Current Biology.
Of the fish with a normal immune system,
65 percent that received predator treatment survived compared with 35 percent
with no predator treatment. Even in the
fish with impaired immune systems, the
predators saved about a quarter of the lot.
“This is the first time that Bdellovibrio
has ever been used as an injected therapy
in live organisms,” Sockett says. “And the
important thing is the injection improved
the survival of the zebrafish.”
The study also pulled off another first.
In previous work, researchers had been
unable to see predation as it happened
within an animal. Because zebrafish
larvae are transparent, study coauthor
Alexandra Willis captured images of
B. bacteriovorus gobbling up S. flexneri.
“We were literally having to run to the
microscope because the process was just
happening so fast,” says Willis, a graduate student in Mostowy’s lab. After the
predator invades, its rod-shaped prey
become round. Willis saw Bdellovibrio
“rounding” its prey within 15 minutes.
Twelve different bacteria,
most gram-negative (blue),
pose the greatest threat to
human health, according to the
World Health Organization,
because they resist multiple
antibiotics. In laboratory tests,
Bdellovibrio bacteriovorus has
shown effectiveness against
four (marked with asterisks).
Priority 1: CRITICAL
s Acinetobacter baumannii*
s Pseudomonas aeruginosa
Priority 2: HIGH
s Enterococcus faecium
s Staphylococcus aureus
s Helicobacter pylori
s Campylobacter spp.
s Neisseria gonorrhoeae
Priority 3: MEDIUM
s Streptococcus pneumoniae
s Haemophilus influenzae
s Shigella spp.*
SOURCES: WHO; A. DASHIFF ET AL/
J. APPLIED MICROBIOL. 2010
Under the microscope, the predatory bacterium Bdellovibrio enters its
larger prey, Salmonella enteritidis. In one study, the predator decreased
Salmonella infection in young chickens.