Re: Phages - if you want to read more

[Guest guest]

Hi pjeanneus - just to help eliminate any potential confusion or

doubt, given the recent postings on phage therapy. While it does

mention the use phage therapy here in the US in the 1940's, the news

article that you have posted is about the behavior of lysogenic

phages. Lysogenic phages are not used in phage therapy. Many

potential patients, journalists, and even microbiologists get

confused or don't understand this difference. It is an apples and

oranges comparison - both are fruit, but they do have very different

characteristics.

Here are links to a large number of peer-reviewed scientific

journals, for anyone interested in further reading about Phage

Therapy:

http://www.phageinternational.com/phagetherapy/humantests.htm

http://www.phageinternational.com/phagetherapy/whitepapers.htm

There's navigation to more sections of material on the left side of

the page.

>

> ALL THE WORLD'S A PHAGE

> Viruses that eat bacteria abound-and surprise BY JOHN TRAVIS

Science

> News, 7/12/03, v164, p26

>

> Smaller than bacteria, some of them look like microscopic

spacecraft.

> You can find them almost anywhere: under a rosebush or miles out to

> sea. These strange entities are bacteriophages, viruses that prey

> upon bacteria, and there's a staggering number of them. A pinch of

> soil or drop of seawater, for example, contains many millions of

> bacteriophages.

>

> " They're nature's most successful experiment, " says Marisa Pedulla

of

> the University of Pittsburgh. " They outnumber all the bacteria, all

> the humans, whales, trees, et cetera, put together. "

>

> Bacteriophages, also known simply as phages, came to light around

90

> years ago, when two European scientists independently discovered

that

> there are viruses that kill bacteria. Like an Apollo spacecraft

> landing on the moon, these viruses settle onto the surface of a

> bacterium. Next, they inject their genes. They reproduce inside the

> microbe, and eventually their multitudinous descendants explode out

> of the host.

>

> One of the discoverers of these odd viruses was Felix d'Herelle of

> the Pasteur Institute in Paris. He coined the word bacteriophage,

> which translates to " eater of bacteria, " and began to promote the

> viruses as treatments for infectious diseases, such as cholera and

> bubonic plague, caused by bacteria.

>

> Because of inconsistent results, phage therapy never took root in

the

> United States, especially after powerful antibiotics such as

> penicillin emerged. Yet many physicians in thef ormer Soviet Union

> continue to use bacteriophages. And with the rise of antibiotic-

> resistant bacteria, some investigators and biotech firms in the

> United States are trying to resurrect d'Herelle's dream (SN:

6/1/96,

> p. 350).

>

> Bacteriophage researchers, however, say that these viruses are of

> interest beyond medicine. At this year's American Society for

> Microbiology meeting in Washington, D.C., in May, bacteriophages

> dominated the agenda of several symposia, only one of which was

> focused on medical therapy. Several talks concentrated on the total

> number of bacteriophages in nature and their impact on bacteria and

> the environment in general. Another series of lectures revolved

> around phages that can make bacteria more virulent (see box, page

> 27). And a number of talks made the point that bacteriophages have

an

> amazing amount of genetic diversity and possess an untold number of

> novel genes.

>

> Bacteriophages represent a " vast, untapped wealth of genetic

> information, "

> says Pedulla. They're " the pinnacle of creation, " adds Pedulla's

> colleague Graham Hatfull, a Medical Institute

> investigator at the University of Pittsburgh. " Phages represent the

> major form of life in the biosphere. "

>

> THEY'RE EVERYWHERE Bacteriophages are drawing renewed interest in

> part because scientists are only now coming to appreciate how many

of

> these viruses exist. It was just over a decade ago that scientists

> realized the amazing number of phages in oceans, Curds Suttle of

the

> University of British Columbia in Vancouver recalled at the recent

> microbiology meeting.

> The realization occurred after several investigators training

> powerful transmission electron microscopes on drops of seawater and

> that viral particles, most of them bacteriophages, flooded the

images.

>

> " Believe it or not, nobody had looked before, " says Suttle. " On

> average, there are 50 million viruses per milliliter in seawater.

The

> question is, What the heck they're doing there? "

>

> Microbiologists then documented similar, and even higher,

> concentrations of phages in soil samples. This led to estimates of

> [lO to the 31] bacteriophages worldwide, a staggeringly large

number

> that many scientists initially dismissed. " We can't wrap our brains

> around it, " says Pedulla.

> " If phages were the size of a beetle, they would cover the Earth

and

> be many miles deep. "

>

> An independent line of reasoning, however, lends support to such a

> phage tally. Other microbiologists have recently estimated the

planet

> harbors[10 to the 30] bacteria. If there are 10 phages for every

> bacterium, a reasonable assumption according to Hatfull, then [10

to

> the 31] is a fair estimate for the number of bacteriophages in the

> world.

>

> These plentiful viruses could have a profound impact on their

> environment, especially in water. According to estimates put forth

by

> Suttle, phages destroy up to 40 percent of the bacteria in Earth's

> oceans each day. In doing so, bacteriophages may influence the

> oceans', and perhaps the entire world's food supply by limiting the

> volume of bacteria available for other organisms to eat. Bacteria

> destroyed by phages fill the water with organic matter that's

either

> consumed by other bacteria or settles to the ocean floor.

>

> " If we've got 40 percent of bacterial cells dying each day, that's

> certainly going to be important to carbon cycling, " says Suttle.

> Viruses are " major players " in the global exchange of carbon

between

> organisms and the environment, he says.

>

> " Phages, being so numerous and such excellent predators of

bacteria,

> are going to be very involved in bacterial turnover. That's a large

> amount of carbon being recycled, " agrees Pedulla.

>

> WHAT'S INSIDE Almost as staggering as the number of bacteriophages

is

> their genetic diversity, according to scientists at the

microbiology

> meeting.

> " Phages are probably the most diverse things on the planet, " says

> Forest Rohwer of San Diego State University.

>

> Scientists usually study a phage's DNA after it has reproduced

within

> a bacterial host. This provides many copies of a phage's genome,

> enabling researchers to read the virus' full genetic sequence. The

> strategy, however, may limit the types of phages examined, since up

> to 99 percent of bacteria have yet to be grown in a laboratory

> environment,

>

> Rohwer's group has instead directly isolated individual

> bacteriophages free-floating in the ocean waters around San Diego

and

> La Jolla, Calif.

> Given curren tDNA-analysis techniques, having a single copy of a

> phage doesn't permit a complete reading of its genome, but the

> investigators can determine the sequence of a few fragments of its

> DNA, With this approach, Rohwer and his colleagues compiled nearly

> 2,000 of these partial sequences from seawater phage genomes and

ran

> them through a computer database of all known genetic sequences of

> plants, animals, fungi, bacteria, viruses, and other microbes. Only

> 28 percent of the phage sequences bore similarities to previously

> documented genes. " Most phages' sequences are unknown, "

> concludes Rohwer.

>

> With the help of high school students in Pennsylvania and New York,

> Hatfull and Pedulla have reached a similar conclusion. Working with

> R.

> s, a Medical Institute investigator at Albert

> Einstein College of Medicine in New York, and s' sister,

Debbie

> s-Sera, who is a high school biology teacher in Pennsylvania,

> Hatfull and Pedulla asked the teenagers to take soil samples.

>

> The students collected soil from barnyards, gardens, and even the

> monkey pit at the Bronx Zoo. The scientists then taught the

students

> how to isolate a bacteriophage from the soil by growing the viruses

> in Mycobacterium smegmatis, a harmless bacterial relative of the

> microbe that causes tuberculosis.

>

> " We guarantee them that the bacteriophage they find will never have

> been discovered before. We know that because the diversity is so

> high, and we've never isolated the same bacteriophage twice, " says

> Hatfull.

>

> In the April 18 Cell, Hatfull and his professional and teenage

> collaborators describe the genomes of 10 soil-dwelling

bacteriophages

> that they had isolated. Of the more than 1,600 genes that the team

> identified, about half are novel, that is, they don't match any

> previously described genes in any other organism. " For a very large

> number of genes, we just don't have a clue what they do. They don't

> look like anything else we've seen before, " says Hatfull.

>

> The University of Pittsburgh team has also recently deciphered the

> DNA sequence of a bacteriophage with a relatively massive genome.

> Known as bacteriophage G, this virus has nearly 700 genes, many

more

> than some bacteria. And the proteins encoded by almost 500 of those

> genes don't match any known proteins, the scientists discovered.

>

> Equally bewildering, however, are some of the newfound

bacteriophage

> genes that do have matches. One phage contains a gene for a

molecule

> that resembles a human protein called Ro. People with the

autoimmune

> disease known as lupus often have antibodies to Ro, Hatfull points

> out.

>

> The phage finding raises the possibility that the virus has a role

in

> lupus. There's been conflicting evidence about whether bacterial

> infections can trigger the disorder, notes Hatfull. Perhaps, he

says,

> it takes the combination of a bacterium and a certain phage.

>

> Another genetic puzzle comes from a phage called Rosebush, which a

> high school student isolated from the soil around such a plant. It

> has two genes resembling those used by many animal immune systems

to

> defend against mycobacterial infections such as tuberculosis and

> leprosy. Other phages contain genes for proteins that the

> mycobacteria produce to manipulate immune responses in their hosts.

> All these phage genes may influence how the microbes cause illness,

> the scientists suggest.

>

> " We see these [genes], and we don't know what they do or why

they're

> there.

> Speculation becomes rife, " says Hatfull. " All we can say is that

> there are genes that we didn't really expect " in bacteriophages.

>

> If that sounds as if Hatfull is saying that he and his colleagues

> remain largely ignorant when it comes to phages, so be it. " I can't

> think of a better word to describe our state of knowledge of the

> bacteriophage population, " he admits. " We are thoroughly ignorant. "

>

>

>

> Phages Behaving Badly

> Viruses can control how dangerous some bacteria are

>

> For almost a century, some physicians have championed the medical

> uses of bacteriophages, but others have been sobered by these

> viruses' darker side.

> Acting as gene-delivery vans, phages can shuttle genetic sequences

> among different bacterial species and strains-and that can be bad

> news for people.

>

> Not all phages destroy the bacteria they invade-at least not

> immediately.

> Some infect bacteria and then lie dormant. The phages sometimes

> insert their own genes, and any they've acquired by reproducing

> inside other bacteria, into the chromosomes of their new host.

These

> phage-delivered genes make some bacteria dangerous, scientists have

> found.

>

> In the 1950s, for example, investigators realized that the

bacterium

> Corynebacterium diphtheriae causes the upper respiratory illness

> known as diphtheria only if a certain bacteriophage infects the

> microbe. The phage, in fact, contains the gene for the toxin that

> triggers diphtheria. A similar story emerged in the 1990s for

> cholera. This deadly disease is attributed to infections by Vibrio

> cholera, but it's actually bacteriophages genes inside the

bacterium

> that carry the instructions for cholera toxin (SN; 6/29/96, p. 404).

>

> More recently, M. Musser of the National Institute of Allergy

> and Infectious Diseases in Hamilton, Mont., and his colleagues have

> fingered phages as co-conspirators with bacteria known as group

> AStreptococcus (GAS) in illnesses ranging from simple sore throats

to

> heart-damaging rheumatic fever and deadly toxic shock syndrome.

When

> the researchers probed the full genetic sequences, or genomes, of

> several GAS strains, they were surprised to find that a significant

> part of each one's genome consists of phage genes, indeed,

> bacteriophages are the major source of genetic differences among

GAS

> strains and seem to account in large part for strain differences in

> virulence, Musser reported in May at the American Society for

> Microbiology meeting in Washington, D.C.

>

> Last year, for example, his team determined that the GAS strain

M18,

> which causes acute rheumatic fever, contains phage genes that

encode

> toxins, but that another strain, which causes strep throat, doesn't

> have those genes

> (SN: 3/30/02,p. 198). The investigators also reported in the July

> 23,2002 Proceedings of the National Academy of Sciences that M3, an

> unusually deadly strain of GAS that produces toxic shock syndrome,

> has yet a different set of phage genes. And in the Feb.18, 2003,

> issue of that journal, Musser and his colleagues revealed that when

> certain immune cells begin to engulf GAS bacteria, the microbes

> activate several phage-derived genes. The function of these genes

> remains unknown, but they appear to be part of the bacterium's

> coordinated response to avoid destruction.

>

> Scientists have also recently discovered that bacteriophages may do

> more than just hand over toxin genes to a bacterium-sometimes, they

> control the release of those toxins. Take the case of Escherichia

> coli, a normally harmless gut bacterium. Strains of E. coli that

> produce a molecule known as Shiga toxin can cause a deadly form of

> food poisoning. The Shiga-toxin gene turns out to be a part of a

> phage genome that has integrated itself into the DNA of some E.

coli

> strains. The toxin gene becomes active only when phage begin to

> reproduce inside an E, coli, says K. Waldor of Tufts

> University School of Medicine in Boston.

>

> Moreover, intact bacteria carrying the gene don't secrete Shiga

toxin

> into people. It's the rupture of the bacterial cells by phages that

> releases the toxin, Waldor and his colleagues report in the May

2002

> Molecular Microbiology. If there's a mutation in the gene that the

> bacteriophages use to disrupt bacterial membranes, the toxin merely

> builds up inside the E.

> coli.

>

> " Phages not only disseminate virulence genes but also regulate the

> production of the virulence factors, " says Waldor.

>

> This discovery has brought a disconcerting fact about certain

> antibiotics to light. Fluoroquinolones, the class of antibiotics

that

> includes the anthrax-fighting drug Cipro, actually trigger the

> activity of phage genes-and thus can increase production of Shiga

> toxin, notes Waldor.

>

> In the June infection and Immunity, F. Prescott of the

> university of Guelph in Ontario and his colleagues say that fluoro-

> quinolones also induce the activity of a phage genome that

typically

> lies dormant within Streptococcus canus, a bacterium that normally

> harmlessly infects dogs and some other animals. The recent use of

> these antibiotics in dogs may therefore explain why veterinarians

> have recently reported some severe cases of toxic shock syndrome

and

> flesh-eating infections in dogs infected with S. canus.

>

> Prescott wonders, " is our use of certain antibiotics helping to

> spread phages, which may also encourage the spread of virulence

> genes? " -J.T.

>

[Guest guest]

Ah shucks, you mean we can't just go jump in the Ganges and get cured

of all our diseases? Thanks for posting these links. And you can call

me " a. " I am too lazy to change my old stock trader arrogant ass

name of " pjeanneus " here on .

Obviously I don't know all that much.

a

>

> Hi pjeanneus - just to help eliminate any potential confusion or

> doubt, given the recent postings on phage therapy. While it does

> mention the use phage therapy here in the US in the 1940's, the

news

> article that you have posted is about the behavior of lysogenic

> phages. Lysogenic phages are not used in phage therapy. Many

> potential patients, journalists, and even microbiologists get

> confused or don't understand this difference. It is an apples and

> oranges comparison - both are fruit, but they do have very

different

> characteristics.

>

> Here are links to a large number of peer-reviewed scientific

> journals, for anyone interested in further reading about Phage

> Therapy:

>

> http://www.phageinternational.com/phagetherapy/humantests.htm

> http://www.phageinternational.com/phagetherapy/whitepapers.htm

>

> There's navigation to more sections of material on the left side of

> the page.

>

[Guest guest]

a

How did you go with those cultures? You should go back and read my

connect the dots post... you seemed to jump up and fit the criteria

to a T. All it took was someone poking your infection and it reared

it's ugly head.Incredable how one eyed some people become with all

the literature they read and try and comprehend.

> >

> > Hi pjeanneus - just to help eliminate any potential confusion or

> > doubt, given the recent postings on phage therapy. While it does

> > mention the use phage therapy here in the US in the 1940's, the

> news

> > article that you have posted is about the behavior of lysogenic

> > phages. Lysogenic phages are not used in phage therapy. Many

> > potential patients, journalists, and even microbiologists get

> > confused or don't understand this difference. It is an apples and

> > oranges comparison - both are fruit, but they do have very

> different

> > characteristics.

> >

> > Here are links to a large number of peer-reviewed scientific

> > journals, for anyone interested in further reading about Phage

> > Therapy:

> >

> > http://www.phageinternational.com/phagetherapy/humantests.htm

> > http://www.phageinternational.com/phagetherapy/whitepapers.htm

> >

> > There's navigation to more sections of material on the left side

of

> > the page.

> >

>