Drug Resistance, Explained

By Marlene Zuk

Marlene is a professor of biology at the University of California at Riverside and an expert in germs and bug sex, among other specialties. At a time when hospital infections are at an all-time high and a new resistant strain called MRSA is making headlines, I asked Dr. Zuk to tell us more about how we kill the germs in our lives. Dead is dead, right? Here’s what she had to say. — Tara Parker-Pope

People can be forgiven for wondering what difference it makes how we kill microorganisms. After all, soap or bleach kills bacteria, and so does penicillin. So why does it matter exactly how you kill them?

It does matter, and the reason for the consequences of killing bacteria with penicillin or killing them with Ivory has to do with evolution. Furthermore, I suspect that part of the confusion in the mind of the public lies in the use of euphemisms like “develop” and “change through time,” rather than what we really mean, which is evolve. Bacteria don’t “develop” resistance, as if it were a muscle nurtured by going to a microbial gym. Instead, they had it all along, or more accurately a small proportion of them did. The process of natural selection, the same one that brought us a four-chambered heart and different sizes of beaks on Galapagos finches, does the rest.

Antibiotics mainly kill bacteria by targeting components in the cell wall, a structure that surrounds bacteria but which our own cells lack. Antibiotics are highly selective — unlike soap and water, which get rid of bacteria indiscriminately, through mechanical means. When you take an antibiotic, a few of the bacterial cells in your body already happen to have genes that enable them to be resistant to it, just by random chance. You have many millions of bacteria, so it’s not too surprising that they vary, the way a big city will tend to have at least a few people with unusual eye color, exceptionally small feet or any other characteristic. If you don’t take the whole course of antibiotics, say the 5 or 7 or 14 days your doctor recommends — or sometimes even if you do — enough of the resistant bacteria may remain to establish a new infection.

And they multiply incredibly quickly, leaving their equally resistant progeny in much greater numbers. The resistant bacteria will spread the way bacteria do, but now they will outnumber the vulnerable ones in the population. Then, when the same antibiotic is used again, it can’t gain a toehold because a far greater proportion of the newly-produced bacteria are unaffected by its use. The bacteria have evolved. Not taking a full course of antibiotics, or taking them when they can do no good, as with viral infections like colds or flu, hastens the selection of the resistant germs. In contrast, although soap and water don’t completely annihilate the bacteria either, they aren’t selective. The bacteria that remain are genetically similar to the ones that went swirling down the drain, and so their offspring are equally vulnerable to the next scrubbing. It’s like the difference between ethnic cleansing and dropping a bomb on a city; the population will look very different following one compared to the other, and using a bomb once doesn’t compromise the ability to use one again. So using soap or bleach-based cleansers is good, but inappropriate application of antibiotics will be worse than ineffective because it drives evolution.

And yet we’ve been acting as if natural selection and evolution do not happen. As microbiologists Dan Andersson and Bruce Levin bluntly stated in the scientific journal “Current Opinion in Microbiology” almost 10 years ago: “The use of antibiotics by humans can be seen as an evolutionary experiment of enormous magnitude.” We’re seeing the results of that experiment now, with MRSA just the tip of the iceberg. Economic costs of drug resistance — longer hospital stays, use of more expensive alternative medications and higher death rates — have been estimated at anywhere from $150 million to $30 billion each year, depending on exactly how you crunch the numbers.

What do we do? For starters, we all have to understand the crucial role that evolution plays in our lives. Doctors need Darwin, and the media has to stop using vague terminology that makes it sound as if bacteria were suddenly, inexplicably motivated to deter penicillin through spite.

Scientists are also experimenting with altering essential proteins in hosts that bacteria use to mount infections. Right now they’re using mice that have genetic mutations that make the proteins inaccessible to the bacteria. It’s not clear exactly how this would be applied to people, but these treatments wouldn’t use conventional antibiotics and hence might be less subject to evolving resistance. Early days, but hopeful.

A few years ago the World Health Organization published this anonymous bit of doggerel titled “The History of Medicine.”2000 B.C.
– Here, eat this root. A.D. 1000
– That root is heathen. Here, say this prayer. A.D. 1850
– That prayer is superstition. Here, drink this potion. A.D. 1920
– That potion is snake oil. Here, swallow this pill. A.D. 1945
– That pill is ineffective. Here, take this penicillin. A.D. 1955
– Oops . . . bugs mutated. Here, take this tetracycline. 1960-1999
– 39 more “oops.” Here, take this more powerful antibiotic. A.D. 2000
– The bugs have won! Here, eat this root.

Dr. Zuk is the author of “Riddled with Life: Friendly Worms, Ladybug Sex, and the Parasites That Make Us Who We Are.”

Source:
http://well.blogs.nytimes.com/2008/03/27/drug-resistance-explained/
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