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Monday, April 18, 2005


A Different Kind of Leech

It was 1962 Berlin, and Heinz Stolp had just run out of membrane filters. Stolp was attempting to isolate bacteriophages that would kill plant pathogens by filtering various soil solutions and applying the filtrate to a lawn of bacteria in a petri dish. The filters had 0.2 micron pores which would let bacteriophage but not other larger particles (such as bacteria) through. If the filtrate contained bacteriophages, they would kill the bacteria if added to the petri dish. This can be observed by the plaques or zones of dead bacteria on the lawn. But Stolp had no more 0.2 micron filters so instead, he used a sintered glass filter which had pores as large as 1.35 microns.

The filtrate was layered on a lawn of Pseudomonas phaseolicola (a scourge of bean plants) and left to incubate overnight. The next day, Stolp didn't see any phage plaques on the bacterial lawns and concluded that that particular experiment didn't work. But instead of immediately throwing the plates away, he left them on his lab bench. Two days later, he happened to glance at the plates again and was surprised that this time, there were plaques.

The plaques were isolated and mixed into a solution that was layered on another lawn of bacteria. Again, the plaques didn't appear until two or three days later which really was strange behavior. Bacteriophages usually lyse bacteria by 24 hours. Stolp found the answer to this puzzle when he examined the plaque under a microscope: tiny, fast moving microbes were attacking and killing the larger Pseudomonas like a spray of bullets intent on making a messy end for its victim.

Stolp and his colleague Mortimer Starr also isolated these tiny predatory microbes from other soil samples and named them Bdellovibrio bacteriovorus (bdello: leech, vibrio: curved, bacteriovorus: bacteria eater). Later researchers discovered Bdellovibrio in a variety of environments--from the aquatic to the human--an indication that they are rather common, perhaps even in our guts. They're around 0.2-0.5 microns wide and 0.5-2.5 microns long, small enough to get through that glass filter. But culturing them is difficult. Unlike other bacteria, they cannot make their own food from the raw materials of conventional media. They depend on prey bacteria to survive.

Bdellovibrio life cycle
Image: Max Planck Institute for Developmental Biology/Rendulic, Berger and Schuster
Considering their size, the Bdellovibrio are super swimmers, reaching up to 160 microns per second. During attack-phase, flagella whip into movement and guided by chemotaxis, Bdellovibrio "sniff out" nearby bacterial prey and torpedo themselves toward their victims. In the next stages, they collide with their prey, attach to the cell surface and enter the prey periplasm by boring a hole in the outer membrane of the prey, squeezing themselves through the opening, and resealing the pore. Once inside the periplasm, a Bdellovibrio multiplies and the prey becomes a bloated structure called the bdelloplast. And when all of the prey cytoplasm is consumed, the Bdellovibrio break out of the bdelloplast to seek more prey.

It's sort of like a microbe version of the movie Alien. Imagine the alien burrowing into your skin, eating your insides, and finally busting out of your spent shell by dissolving your skin. What a gruesome way to die.

One could almost feel sorry for the terrible fate that meet Bdellovibrio prey. Almost. See, Bdellovibrio primarily prey on bacteria that we consider pathogens. Not only do they prey on plant pathogenic Pseudomonas as Stolp observed but also other Pseudomonas species that infect burn wounds and the lungs of cystic fibrosis patients. Some other human pathogens that can become prey are E. coli, Salmonella, and Legionella. On the other hand, Bdellovibrio cannot grow in eukaryotic cells which makes them completely harmless to us.

Is it possible, then, that this may be a case of that old Arab proverb, "the enemy of my enemy is my friend"? Certainly the recent scientific literature seems headed that way. In Nature Reviews Microbiology, Sockett and Lambert discuss how Bdellovibrio may be used as a therapeutic agent. There are several reasons to recommend using this microbe as an antibiotic. Bdellovibrio can infiltrate biofilms, a protective matrix of polysaccharide some bacteria shield themselves with, that stubbornly cling to implanted devices like catheters. These microbes are also resistant to chemical antibiotics so they could be used in combination with drugs like penicillin to vigorously fight infection. And although Bdellovibrio contains lipopolysaccharide (LPS)--a potent stimulator of the immune response present in gram-negative bacteria--on its cell wall, the Bdellovibrio LPS is significantly different than other gram-negative LPS that it is unlikely that it would cause a severe reaction in the human immune system.

So just as we now use macroscopic blood-sucking leeches as FDA approved medical devices, these microscopic "leeches" may prove to be a "living antibiotic" as potent as a top-of-the-line chemical arsenal.


[posted by S. Y. Affolee on 4:16 PM : ]



Comments:
that picture wasn't easy to make, try citing it.
 
so...i'm googling microscopic leeches because when my sink got clogged this morning guess what floated to the sink bowl? little teeny tiny 10mm little flatworm-things that look exactly like leaches only very small and flat. i'm still wondering-but i'm also picking up some bleach and drano on the way home.

jlouisesadler@gmail.com

very curious to figure this one out.
 
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