[OT] Evolution at Work: Watching Bacteria Grow Drug Resistant

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SCIENCE JOURNAL

By ROBERT LEE HOTZ

Evolution at Work: Watching Bacteria Grow Drug Resistant

June 8, 2007; Page B1

Day by day, the doctors unwittingly helped the bacteria infecting their

young heart patient to evolve. The more intensively they treated his affliction

with antibiotics, the more the microbes resisted the therapy.

In a strict medical sense, the young man, identified only as Patient X,

died of complications from a congenital heart ailment and a Staphylococcus

aureus infection.

More broadly, evolution killed him.

The life-and-death struggle inside his infected heart was driven by the

same evolutionary forces of natural selection and adaptation that are causing a

pandemic of drug-resistant diseases world-wide. The emergence of such immunity

among infectious diseases is one of the most well-documented problems in modern

public health. Until now, however, researchers knew little about how bacteria

multiplying inside the human body overcome the drugs designed to control them.

Last month, an international team of 11 scientists, led by biologists at

Rockefeller University in New York, for the first time identified the genetic

changes that occurred as Staph bacteria developed resistance to successive

antibiotics, step by step, in the living test tube of a sick man. To document

events inside these virulent cells, Rockefeller University biologist

Mwangi and his colleagues analyzed the infection's genetic code as it changed in

a series of blood samples taken during the patient's stay. Their work, reported

in the Proceedings of the National Academy of Sciences, details how the

molecular mechanics of survival are strengthening many deadly diseases.

Patient X died in October 2000 after a 12-week hospital stay. His case

comes to light now because researchers only recently developed the computational

techniques needed to sequence generations of bacteria. The hospital, which also

wasn't identified, gave the patient's Staph samples to the Rockefeller team for

research purposes. The techniques still are too slow and expensive for clinical

use.

When Patient X was admitted to the hospital, he was already suffering from

a Staphylococcus aureus infection, but it was still vulnerable to antibiotics.

During treatment, however, the bacteria quickly developed stronger resistance to

four antibiotics, including vancomycin, the drug of last resort for intractable

infections, the scientists reported. As living bacteria, the Staph were driven

to survive.

Every time the patient took his medicine, the antibiotics killed the

weakest bacteria in his bloodstream. Any cell that had developed a protective

mutation to defend itself against the drug survived, passing on its special

trait to descendants. With every round of treatment, the cells refined their

defenses through the trial and error of survival. " It means that during a normal

course of treatment there is an evolutionary revolution going on in your body, "

said Stanford University biologist Plaumbi, author of " The Evolution

Explosion: How Humans Cause Rapid Evolutionary Change. "

These resistant microbes, all disease-producing organisms spawned by the

original infection, quickly accumulated 35 useful mutations. Each one altered a

molecular sensor or production of a protein.

Researchers then matched these gradual genetic changes to increasing

levels of drug resistance, shocked that it took so little to undermine the

foundation of modern infectious-disease control. " We have now really looked into

the belly of the beast and seen the mechanism, " said Rockefeller microbiologist

Tomasz.

Nearly two million people catch bacterial infections in U.S. hospitals

every year and 90,000 of them die -- seven times as high as a decade ago as

germs become immune to almost every antibiotic developed during the past 60

years. The most common is the Staphylococcus bacteria. World-wide, some two

billion people carry these bacteria; up to 53 million people are thought to

harbor antibiotic-resistant forms.

On average, people who contract Staph infections stay in the hospital

three times as long and face five times the risk of dying. But these infections

are becoming more prevalent outside hospitals. Antibiotic-resistant Staph

infections increased almost sevenfold from 2001 to 2005, researchers reported

last week in the Archives of Internal Medicine. Contagions such as tuberculosis,

pneumonia and bubonic plague also are becoming immune to the drugs that once

kept them at bay.

The death of Patient X highlights the speed of natural selection in

fostering antibiotic resistance. " When you talk about the evolution of an arm or

an eye or a species, you might be talking about millions of years. You can get

bacteria resistant in a week, " Dr. Mwangi said.

The Rockefeller researchers believe that a better understanding of

evolution will lead to better antibiotic treatments. They want to disable the

genes that allow these disease bacteria to mutate and adapt. The Staph bacteria

that evolved inside Patient X now have such strong defenses that, in recent

tests, they easily withstood even the next generation of clinical antibiotics.

For the time being, the microbes are keeping one step ahead.

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