Bacteria waiting for their movie

This article about the life and power of bacteria creeps me out, but I can foresee a Sci-Fi plot being written from some of the tenets....sounds pretty much like they are beings from another galaxy, in struggle to take over, slowing killing their hosts. Or something like that...

From the Chicago Tribune Magazine:

When Christopher Reeve died last month of a bacterial infection, he was surrounded by doctors who were powerless to prevent the lethal microbes from overwhelming his body's defenses. ... The problem is increasingly alarming because of bacteria's well-known ability to develop resistance to even the most up-to-date antibiotics. Although many patients contract infections they didn't come into the hospital with, many also bring along germs that have been living peacefully inside them for their entire lives and which suddenly flare up. These patients often die because no drugs work against the microorganisms.

But continually inventing new antibiotics isn't the answer, says Dr. John Alverdy, a gastroenterological surgeon and researcher at the University of Chicago. Instead of trying to kill bacteria, Alverdy is developing an approach that, in effect, makes them feel safe and content inside their human host. If they don't sense a need or opportunity to attack, he reasons, they remain happy campers and no infection occurs.

A similar problem exists with the most deadly pathogen of all, Pseudomonas aeruginosa, the one that's getting Alverdy's attention. It is antibiotic-resistant, extremely quick to act and metabolically diverse; that is, it can grow anyplace it finds one of the vast array of nutrients it can subsist on. It is found almost everywhere, including drinking fountains, faucets, streams, moist soil and the surface of vegetables.

"The average person is exposed to Pseudomonas aeruginosa every day," says Dr. Alan Hauser, assistant professor of microbiology and immunology at Northwestern University.

An estimated 70 percent of those infected with it die. It claims the lives of 60 percent of patients in burn units, 50 percent of AIDS patients and most of those with cystic fibrosis. Alverdy reasoned that he should start with this most wanton of killers. "If I could defeat the worst [form of bacteria], then I could apply that template of discovery to defeat many of the others," he says.

Those include germs like the ones that cause bacterial pneumonia and are now 20 percent resistant to penicillin. In some cases, says Salyers, half the bacteria of a particular species are resistant to at least one antibiotic. "What's at stake," she says, "is the possible loss of the effective use of antibiotics. This would be the first time in history that a cure was actually lost."

Alverdy argues that killer bacteria are innately benign and only turn virulent when they sense the host's tissue defenses are weakened, threatening their environment-the intestines, in the case of Pseudomonas aeruginosa.

"When the host is traumatized, bacteria like Pseudomonas aeruginosa are like rats leaving a sinking ship," says Dr. James Shapiro, professor of genetics at the U of C and an expert on bacterial behavior. "It makes sense for bacteria in a dying host to escape" by killing the host with its lethal toxins.

Based on pioneering research by Shapiro showing that bacteria are social organisms that can communicate with each other, Alverdy and his partner, Dr. Eugene Chang, professor of medicine at the University of Chicago, developed a compound that interferes with those communications.

In a recent study, they induced stress in laboratory mice and then introduced Pseudomonas aeruginosa directly into their intestines. All the mice died of the resulting infection, called gut-derived sepsis. However, when Alverdy and Chang treated the mice with their compound, a form of polyethylene glycol, the mice were completely protected. Amazingly, a virulent attack was prevented though not a single bacterium was killed.

Chang explains that the high-molecular-weight polyethylene glycol they used acts as an artificial mucus. A non-toxic polymer, it coats the bacteria and intestines and blocks the signals the microbes would otherwise send each other to mass for war and release lethal toxins. The study was recently published in the journal "Gastroenterology.


Alverdy believes his study shows that the strategy of foiling bacterial communication holds more promise than using antibiotic drugs to fight an attack after it starts.

"Drug companies have spent billions of dollars trying to manipulate inflammation after it is initiated and have universally failed," says Alverdy. "Why not interdict before it occurs?"

Antibiotic treatment merely creates a never-ending, escalating arms race between medical researchers and bacteria, he says. And the bacteria always stay one step ahead of advances by quickly generating a genetic defense against the drugs. "Because generations of bacteria have faced multiple attempts at their elimination," he notes, "they have evolved the means to perpetually develop and refine their virulence capabilities."

Able to divide every 20 minutes, a bacterial cell could produce 5 billion progeny cells in just under 11 hours. "In the short term, we may be more clever than the bugs," says Alverdy, "but in the long term, they are more clever than we are . . . . We are just starting to understand how clever they are about changes in our biochemistry."

Shapiro agrees: "Bacteria are small, but they're not stupid," he says, noting that bacteria are very sophisticated in their information processing. "Every time a bacterium divides, tens of millions of biochemical processes have to be coordinated and controlled. The bacterial cell is the ultimate, just-in-time production facility."

This cell-to-cell communication is what allows Pseudomonas aeruginosa to make decisions about whether to assemble and secrete lethal toxins, Shapiro's research shows. "A single bacterium would not take on a host," he says. "They can sense their population density. When they sense how many of their own group are around and realize that the numbers are sufficient to kill the host, they attack."

On average, we have 500 to 700 species of bacteria living in or on our bodies, 3 trillion in all. A newborn baby has no "flora," a term used to describe the full array of microbes that inhabit our intestines and other structures. But around the 7th to 10th day the baby acquires all the flora it will have for the rest of its life from the environment.

The trillions of bacteria live in our intestines, sharing a kind of peaceful coexistence. But certain stresses, like surgical trauma, send signals that can cause bacteria to become virulent.

And a hospital intensive-care unit "is a strange new world for the bacteria," Alverdy says. "It's as though the bacteria is saying, 'I've been in your body for 50 years, and now I'm in an intensive care unit. They're attacking you with drugs. They won't let you eat, won't let you poop. They put the food in your veins so I have to go into your bloodstream to eat.' "

Although the bacteria have been alerted to the fact that the host is diseased and vulnerable, they have no reason to attack until the severity of the illness and the harshness of the therapies converge to create an alarming change in the bacterial environment. At that point they sense that the host has become a liability and signal each other to ascertain if there are enough of them to invade, inflame or kill the host. If the numbers are sufficient, they launch an assault.

Conversely, says Alverdy, when patients in the ICU are fed again, taken off morphine and begin to have bowel movements, the infection disappears. This, he believes, is because the bacteria sense that the host's health is improving.

Bacteria know that their survival is dependent on their host's survival, says Alverdy. "Organisms have a history of jumping to new hosts to survive, having moved, historically, from crops into cows and into man. A bacteria that kills its [sick] host has the chance that a bird will eat the carcass and ingest it, giving it a new lease on life."

Alverdy, Chang and others have formed a company in an effort to continue their research. "We have just had an offer in the millions of dollars for the licensing rights to high molecular weight [polyethylene glycol]," says Alverdy. They are awaiting approval from the FDA to begin human clinical trials. The first two populations that will undergo the trials are bone marrow transplant patients and children at risk for a type of colitis.

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This page contains a single entry by swanksalot published on November 14, 2004 6:01 PM.

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