sidecross
04-01-2003, 04:40 AM
Aliens Inside Us: A (Mostly Friendly) Bacterial Nation
April 1, 2003
By JAMES GORMAN
In the movie "Alien," the creature of the title grows
toothy and impatient inside John Hurt, finally bursting
through his stomach in a fit of extreme and bloody pique,
looking something like an albino salamander with fangs. It
promptly scuttles off to become even more obnoxious.
Leave it to the movies to exploit, with an unabashed lack
of subtlety and taste, the nagging fear that there is
something awful inside us. The fear is not without
foundation. Peach trees and watermelon vines will not grow
there, but parasites, worms and cysts will do fine. The
list of potential co-inhabitants is long and gruesome. Any
medical student knows that there is no need to fret about
what lurks under the bed when you can lose sleep thinking
about what lies within.
On a deep level, it is not really the odd parasite that
worries us. The unsettling fact is that each of us, sick
and healthy, could start speaking in the first person
plural, not with the editorial, but the biological "we." We
may not all have multiple personalities, but it is fair to
say that the self some of us try so relentlessly to improve
is really community property.
There is a world within each of us, a living, evolving
ecological system of 500 to 1,000 species of microbes, a
"bacterial nation" in the words of Dr. Jeffrey I. Gordon, a
microbiologist at Washington University in St. Louis. In
fact, by numbers of cells, a human being has 10 times as
many bacteria as human cells. The bacterial cells are much
smaller, which is why we do not look like an overgrown
petri dish.
Nor are we simply hosts to a random collection of bugs. The
bugs appear to be organized. The good news is that they are
on our side - most of them, most of the time. They
function, Dr. Gordon would say, as an organ, or, as they
are commonly called, the gastrointestinal consortium, a
parliament of the bowels.
"I think of it," Dr. Gordon said, "as a life form within us
exquisitely tuned to our biology."
Our internal bacteria help us digest food that otherwise
would simply pass through us. They fend off unfriendly
bacteria and even regulate the development and metabolic
processes of the host.
The presence of these bugs in the gut is well known, but
the nature of these microbes - what they do, what species
they belong to - is still poorly understood. Nobody even
knows how many species inhabit us, partly because they have
not been easy to grow outside of their home environment.
But now, as two papers and a commentary in the current
issue of the journal Science suggest, the powerful
techniques of genomic research are providing new ways to
investigate the lives of these bacterial cells. In separate
reports, scientists describe the genomes of two different,
common bacteria. One is Bacteroides thetaiotaomicron, a
friendly symbiont; the other is a traitorous drug-resistant
variant of Enterococcus faecalis, an otherwise
mild-mannered garden-variety citizen of the
gastrointestinal consortium.
In the new research report, Dr. Gordon, Dr. Jian Xu and six
colleagues, all at Washington University, describe
sequencing the genome of Bacteroides thetaiotaomicron. That
particular bug is ubiquitous in humans and many other
creatures.
"We are not alone in developing co-conspiracies with
bacteria," Dr. Gordon said. He and his co-workers have
conducted much of their work in the mouse gut, because they
can rear mice in a germ-free environment and introduce one
germ at a time.
In past work, the researchers have found that without the
presence of bacteria, blood flow to the intestine does not
develop correctly. The growth of a capillary network is
apparently initiated by the presence of bacteria, either
Bacteroides thetaiotaomicron alone or a sampling of the
full consortium. Without bacteria, digestion and proper
development are impaired.
By sequencing the genome, Dr. Gordon and his colleagues
found many genes devoted to processing carbohydrates that
humans cannot digest. They also discovered genes devoted to
processing some materials produced by the human cells like
mucin. These bacteria graze in the mucous lining of the
intestine. Apparently they do not damage their range-land.
"There's grazing and then there's destruction," Dr. Gordon
said. "And these are good grazers."
Not all is cooperation and mutual back-scratching in
biology, however. Good bugs go wrong. Ancient biological
alliances break down. In another paper in Science, Dr. Ian
T. Paulsen of the Institute for Genomic Research in
Rockville, Md., and 31 other researchers report on the
sequencing of a turncoat genome. The bug in question,
Enterococcus faecalis, is normally a commensal bacteria. In
other words, it lives within us, and we both seem happy
enough about the arrangement, although whether it helps us
is unknown.
But some variants of Enterococcus are dangerous and drug
resistant. They cause infections, particularly in hospital
patients. Dr. Paulsen and colleagues sequenced the first
strain of E. faecalis in the United States that was found
to be resistant to vancomycin, an antibiotic that is often
a drug of last resort.
The sequencing suggests how the bacteria went wrong. Nearly
a third of its genome consists of mobile elements of DNA on
its chromosomes and in self-contained packets called
plasmids. The toxic effects and drug resistance are a
result of this mobile DNA.
Dr. Paulsen said that the greatest significance of the
sequencing was in "finding how much genetic exchange has
gone on in the evolution of this pathogen." It is, he said,
"easy to transfer resistance genes among enterococcus
bacteria and to other things like staphylococcus."
Drug-resistant staphylococcus is a major problem for
hospitals and, Dr. Paulsen said, one or two strains had
"virtually certainly gained resistance genes from an
enterococcus."
In a commentary on the two papers, Dr. Michael S. Gilmore
and Dr. Joseph J. Ferretti at the University of Oklahoma at
Oklahoma City, wrote that the two studies illuminated the
way the consortium worked and what the members were doing.
For instance, Dr. Gilmore said, with B. faecalis, the
research showed "that it devotes a lot of its genetic
material to enzymes that occur on the surface of the cell."
That suggests it is breaking down material for some other
organism, perhaps aiding certain sorts of bacterial
neighbors.
"I'd bet a thousand dollars that those neighbors are
cultivating something that Bacteroides can take advantage
of," Dr. Gilmore said in an interview. It is that kind of
cross talk between bacteria that may be elucidated in
further genomic studies, he said.
The work on Enterococcus suggests what is going on when
strains of bacteria leave the colon, say, and go to another
location where they are damaging to the host. He said
Enterococcus had 130 new genes from other organisms in its
mobile DNA.
"What can you do with 130 new genes?" Dr. Gilmore asked.
"Be more aggressive in the relationship with the host."
Enterococcus might be gaining the ability to move closer to
the small intestine or the urinary tract, that is, to
colonize new areas. To the host, that would mean an
infection.
The possibilities of genomic research into the bacteria of
the gut are almost unlimited. Dr. Gordon suggested that one
could think of the collected genomes of the bacterial
species as a single unit, a microbiome. It would be similar
in size to the human genome on the basis of the amount of
raw DNA. But it would be much larger, 100 times as large,
in terms of actual genes - DNA sequences that code for
proteins.
In the future, Dr. Gordon said, scientists may "discover
novel components of our biology that are modulated by
bacteria." Perhaps obesity or susceptibility to heart
disease may depend on the nature of an individual's
internal bioreactor.
There is no escaping it. Our skin supports a veritable zoo
of small creatures; our gut is home to an alien nation,
except that in reality it is not at all alien. We may or
may not be what we eat, but we certainly are what lives
within us.
"It is important," Dr. Gordon said, "to think of our bodies
as a summation of the metabolic capabilities provided by
our own genome and the microbiome."
Because of the union of those abilities, he said, "we
become a more complete and capable life form."
http://www.nytimes.com/2003/04/01/health/01GUT.html?ex=1050214320&ei=1&en=655d2747f1572eb7
April 1, 2003
By JAMES GORMAN
In the movie "Alien," the creature of the title grows
toothy and impatient inside John Hurt, finally bursting
through his stomach in a fit of extreme and bloody pique,
looking something like an albino salamander with fangs. It
promptly scuttles off to become even more obnoxious.
Leave it to the movies to exploit, with an unabashed lack
of subtlety and taste, the nagging fear that there is
something awful inside us. The fear is not without
foundation. Peach trees and watermelon vines will not grow
there, but parasites, worms and cysts will do fine. The
list of potential co-inhabitants is long and gruesome. Any
medical student knows that there is no need to fret about
what lurks under the bed when you can lose sleep thinking
about what lies within.
On a deep level, it is not really the odd parasite that
worries us. The unsettling fact is that each of us, sick
and healthy, could start speaking in the first person
plural, not with the editorial, but the biological "we." We
may not all have multiple personalities, but it is fair to
say that the self some of us try so relentlessly to improve
is really community property.
There is a world within each of us, a living, evolving
ecological system of 500 to 1,000 species of microbes, a
"bacterial nation" in the words of Dr. Jeffrey I. Gordon, a
microbiologist at Washington University in St. Louis. In
fact, by numbers of cells, a human being has 10 times as
many bacteria as human cells. The bacterial cells are much
smaller, which is why we do not look like an overgrown
petri dish.
Nor are we simply hosts to a random collection of bugs. The
bugs appear to be organized. The good news is that they are
on our side - most of them, most of the time. They
function, Dr. Gordon would say, as an organ, or, as they
are commonly called, the gastrointestinal consortium, a
parliament of the bowels.
"I think of it," Dr. Gordon said, "as a life form within us
exquisitely tuned to our biology."
Our internal bacteria help us digest food that otherwise
would simply pass through us. They fend off unfriendly
bacteria and even regulate the development and metabolic
processes of the host.
The presence of these bugs in the gut is well known, but
the nature of these microbes - what they do, what species
they belong to - is still poorly understood. Nobody even
knows how many species inhabit us, partly because they have
not been easy to grow outside of their home environment.
But now, as two papers and a commentary in the current
issue of the journal Science suggest, the powerful
techniques of genomic research are providing new ways to
investigate the lives of these bacterial cells. In separate
reports, scientists describe the genomes of two different,
common bacteria. One is Bacteroides thetaiotaomicron, a
friendly symbiont; the other is a traitorous drug-resistant
variant of Enterococcus faecalis, an otherwise
mild-mannered garden-variety citizen of the
gastrointestinal consortium.
In the new research report, Dr. Gordon, Dr. Jian Xu and six
colleagues, all at Washington University, describe
sequencing the genome of Bacteroides thetaiotaomicron. That
particular bug is ubiquitous in humans and many other
creatures.
"We are not alone in developing co-conspiracies with
bacteria," Dr. Gordon said. He and his co-workers have
conducted much of their work in the mouse gut, because they
can rear mice in a germ-free environment and introduce one
germ at a time.
In past work, the researchers have found that without the
presence of bacteria, blood flow to the intestine does not
develop correctly. The growth of a capillary network is
apparently initiated by the presence of bacteria, either
Bacteroides thetaiotaomicron alone or a sampling of the
full consortium. Without bacteria, digestion and proper
development are impaired.
By sequencing the genome, Dr. Gordon and his colleagues
found many genes devoted to processing carbohydrates that
humans cannot digest. They also discovered genes devoted to
processing some materials produced by the human cells like
mucin. These bacteria graze in the mucous lining of the
intestine. Apparently they do not damage their range-land.
"There's grazing and then there's destruction," Dr. Gordon
said. "And these are good grazers."
Not all is cooperation and mutual back-scratching in
biology, however. Good bugs go wrong. Ancient biological
alliances break down. In another paper in Science, Dr. Ian
T. Paulsen of the Institute for Genomic Research in
Rockville, Md., and 31 other researchers report on the
sequencing of a turncoat genome. The bug in question,
Enterococcus faecalis, is normally a commensal bacteria. In
other words, it lives within us, and we both seem happy
enough about the arrangement, although whether it helps us
is unknown.
But some variants of Enterococcus are dangerous and drug
resistant. They cause infections, particularly in hospital
patients. Dr. Paulsen and colleagues sequenced the first
strain of E. faecalis in the United States that was found
to be resistant to vancomycin, an antibiotic that is often
a drug of last resort.
The sequencing suggests how the bacteria went wrong. Nearly
a third of its genome consists of mobile elements of DNA on
its chromosomes and in self-contained packets called
plasmids. The toxic effects and drug resistance are a
result of this mobile DNA.
Dr. Paulsen said that the greatest significance of the
sequencing was in "finding how much genetic exchange has
gone on in the evolution of this pathogen." It is, he said,
"easy to transfer resistance genes among enterococcus
bacteria and to other things like staphylococcus."
Drug-resistant staphylococcus is a major problem for
hospitals and, Dr. Paulsen said, one or two strains had
"virtually certainly gained resistance genes from an
enterococcus."
In a commentary on the two papers, Dr. Michael S. Gilmore
and Dr. Joseph J. Ferretti at the University of Oklahoma at
Oklahoma City, wrote that the two studies illuminated the
way the consortium worked and what the members were doing.
For instance, Dr. Gilmore said, with B. faecalis, the
research showed "that it devotes a lot of its genetic
material to enzymes that occur on the surface of the cell."
That suggests it is breaking down material for some other
organism, perhaps aiding certain sorts of bacterial
neighbors.
"I'd bet a thousand dollars that those neighbors are
cultivating something that Bacteroides can take advantage
of," Dr. Gilmore said in an interview. It is that kind of
cross talk between bacteria that may be elucidated in
further genomic studies, he said.
The work on Enterococcus suggests what is going on when
strains of bacteria leave the colon, say, and go to another
location where they are damaging to the host. He said
Enterococcus had 130 new genes from other organisms in its
mobile DNA.
"What can you do with 130 new genes?" Dr. Gilmore asked.
"Be more aggressive in the relationship with the host."
Enterococcus might be gaining the ability to move closer to
the small intestine or the urinary tract, that is, to
colonize new areas. To the host, that would mean an
infection.
The possibilities of genomic research into the bacteria of
the gut are almost unlimited. Dr. Gordon suggested that one
could think of the collected genomes of the bacterial
species as a single unit, a microbiome. It would be similar
in size to the human genome on the basis of the amount of
raw DNA. But it would be much larger, 100 times as large,
in terms of actual genes - DNA sequences that code for
proteins.
In the future, Dr. Gordon said, scientists may "discover
novel components of our biology that are modulated by
bacteria." Perhaps obesity or susceptibility to heart
disease may depend on the nature of an individual's
internal bioreactor.
There is no escaping it. Our skin supports a veritable zoo
of small creatures; our gut is home to an alien nation,
except that in reality it is not at all alien. We may or
may not be what we eat, but we certainly are what lives
within us.
"It is important," Dr. Gordon said, "to think of our bodies
as a summation of the metabolic capabilities provided by
our own genome and the microbiome."
Because of the union of those abilities, he said, "we
become a more complete and capable life form."
http://www.nytimes.com/2003/04/01/health/01GUT.html?ex=1050214320&ei=1&en=655d2747f1572eb7