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1999-08-24 00:11:52

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Cholera 2 (New virii)

Привет All! 

=== Cut === 
Cholera, about the biological version 

June 27, 1996 

Harvard researchers find cholera bacterium may take 
instruction from a virus 

BOSTON-In 1993, as cholera swept through India, scientists were 
faced with a set of perplexing questions: What caused the deadly 
Bengal strain of cholera to reappear? 
Where did the deadly cholera pathogen come from in the first place? 

Scientists have known that the cholera bacterium (Vibrio cholera) 
owes its virulence to two factors: The cholera toxin and another 
protein, TCP pili, which enables it to clump together and burrow 
into the intestines. But how the Vibrio cholera got those deadly 
factors has been a mystery. 

Two Harvard Medical School scientist have found a partial answer 
to this puzzle. It appears that the cholera pathogen responsible 
for the Indian epidemic (Vibrio cholera 01) picked up one of its 
most lethal patches of DNA - the gene coding for the cholera 
toxin - from a virus, CTX phage. 

"Here you have this dumb bacterium-Vibrio cholerae doesn't know how 
to become a pathogen. And the virus instructs it by introducing the 
cholera gene into the bacterial genome. The virus is the smart player 
in the interaction," says John Mekalanos, Higgins Professor of 
Microbiology and Molecular Genetics. He and Matthew K. Waldor, research 
fellow in medicine, announced their findings in the June 28 issue of Science. 

The virus's first clever act is to select its students. It appears to 
introduce the gene for cholera toxin only into those bacteria that 
express the TCP pili protein. 

Once inside the bacterium, the cholera toxin gene is activated by 
the same gene that turns the TCP pili gene on. This gene, known as 
Tox R, is designed to sense the intestinal environment. This 
ingenious arrangement is designed to bestow the cholera toxin gene 
on those bacteria located in an area where it can be used, namely the 

"What this says is, 'Multiply in a sinister place'. You have to bring 
something at the party - TCP pilus - but I'll bring the band and we'll 
have a dance" says Mekalanos. 

One reason the wily virus has eluded scientists' grasp for so long is 
that it belongs to a relatively rare class of viruses, the filamentous 
phages. Unlike other bacterial viruses, filamentous viruses do not kill 
the host cell though they may slow down growth, so there is no visual 
thinning of a bacterial lawn to mark an infection. 

Even if filamentous viruses left a mark, researchers had little reason 
to suspect they were the culprits behind cholera. Filamentous viruses 
have never before been known to donate a fully functioning gene to a 
bacterium. Yet in the series of experiments reported in Science, 
Mekalanos and Waldron show that the CTX phage filamentous virus does 
move from a donor bacterium (Vibrio cholera 01) to a non-virulent 
recipient bacterium, bringing with it all of its genes. Some of these 
viral genes-including the gene for cholera toxin-may be expressed in 
the recipient bacterium. 

In the first set of experiments, the researchers replaced the cholera 
toxin gene of Vibrio cholerae 01 with an antibiotic-resistant gene. They 
then mixed this antibiotic-resistant Vibrio with a recipient bacterium 
marked with a second antibiotic-resistant gene. The recipient bacterium 
was chosen for its ability to produce TCP pili under laboratory 
conditions. They found some recipient bacteria had acquired a resistant 
to both antibiotics, indicating they had, in fact, acquired an extra 
piece of DNA. 

When they isolated and purified the particle of DNA, they found it 
had the long stringy shape characteristic of a filamentous virus. 
It was also single stranded, another hallmark of a filamentous virus. 

To get a better sense of how the virus and bacteria actually interact, 
the researchers repeated the experiment with a recipient bacterium that 
does not produce TCP pili under laboratory conditions. Virtually no 
transfer of the virus occurred. But when they put the same mixture of 
recipient and donor into the gut of a mouse and then measured the 
transfer rate 24 hours later, they found stunning results. "The recipient 
strain is a million times better recipient of a virus in the intestine 
than it is under any laboratory conditions," says Mekalanos. 

The discovery contradicts a long-standing and widely held notion about 
the emergence of infectious disease. Researchers traditionally have 
believed that bacteria pick up their virulence factors outside of the 
human body, in watery sewage systems or in stagnant coastal waters. 
However, it now seems that at least some pathogens originate inside 
the human body. 

"From these data it sounds like the mixing pot may be our own intestines. 
And in a way we're constantly eating foods of various sorts. The body 
is its own little pressure cooker-cooking up, moving genes back and 
forth," says Mekalanos. "This phenomenon that we've uncovered may be 
the tip of the iceberg." 

=== Cut === 

С бестовыми регардами , Kostya Volkov aka Reminder 

* Origin: 2B OR (NOT 2B) = FF (2:4631/17) 
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