Becoming Resistant to Antibiotics A Howto Guide

Try as scientists might to develop new and better antibiotics, bacteria are gaining on them, evolving resistance against every compound science can throw their way. Bacteria, in other words, are pretty good at this evolution thing, and here's why:

1 They reproduce extremely rapidly, and lots of them exist.

1 They've been at it a long time. Antibiotics are common in nature. Penicillin, the first antibiotic in wide use, comes from a fungus, Pennicillium chrysogenum.

1 They are the weapons bacteria and other organisms sometimes use in fighting each other.

Bacteria can gain antibiotic resistance in a couple of ways: by mutations and by gene transfers. The following sections give the details.

Evolution via mutation

As I explain in Chapter 5, evolution by natural selection requires the existence of a variation on which selection can act. The initial source of all variation is the random mutations in an organism's DNA. These mutations occur during the processes of DNA replication (when copies are made) or repair. Basically, whenever an organism is doing something with its DNA, a chance exists that a mistake will occur, resulting in DNA with a slightly different sequence.

Because bacteria reproduce rapidly (sometimes as fast as every 15 minutes), and because so many of them are around, many opportunities are available for these changes in DNA sequence to occur. Put a billion bacteria in a beaker, and come back 15 minutes later; you could find 2 billion bacteria. In the course of duplicating those 1 billion genomes, a substantial number of errors will have occurred. Bacteria's fast, high-density lifestyle gives them an evolutionary edge.

You can observe this phenomenon in the laboratory very easily. An experimenter takes a single bacterium that's known to be sensitive to a particular antibiotic, drops the bacterium into a nice cozy beaker, and lets the bacterium divide. Pretty soon the beaker contains two bacteria, then four, and then eight. By the next day, the beaker contains millions and millions of bacteria, all descendents of the same antibiotic-sensitive parent. Now the experimenter takes these millions of bacteria and exposes them all to the antibiotic. Often, he finds that the beaker now contains resistant bacteria. Mutations have appeared in these bacteria as a result of DNA replication errors, and these mutations confer resistance to the antibiotic. When the remaining bacteria reproduce to fill the flask again, the experimenter ends up with a flask full of antibiotic-resistant bacteria.

Scientists would really like to develop an antibiotic to which bacteria can't evolve resistance, but so far, they haven't had any luck. The process of evolution is so powerful that when scientists change the bacteria's environment by adding antibiotics, they always manage to select for resistant bacteria. In our new antibiotic-drenched world, any bacterium that's a little bit better at surviving in the presence of antibiotics is going to be the one that leaves the most descendents.

4jtJABCi A common misconception is that the addition of the antibiotic leads to the genetic changes that result in antibiotic resistance. But evolution requires that the variation already be present. The addition of the antibiotic didn't cause the bacteria in the beaker to become antibiotic resistant; it just killed all the antibiotic-sensitive bacteria, leaving behind only the bacteria that happened to be antibiotic resistant already.

Evolution via gene transfer

An interesting characteristic of bacteria is that occasionally they acquire genes from bacteria of other species. Yes, that phenomenon is as weird as it sounds. Bacterial reproduction usually involves just dividing in two; no other bacteria is required, and both of the resulting bacteria are (excepting the occasional mutation) genetically identical. Every once in a while, however, a bacterium acquires genes from somewhere else. When it does, it's not too picky about which genes it gets.

An example of this kind of acquisition of new genes is the pathogenic E. coli 0157:H7 (see Chapter 15). E. coli 0157:H7 first came to light after an outbreak at a fast-food establishment; as of late, it's been found in a large number of domestic cattle operations, as well as in the occasional bag of spinach. This nasty version of E. coli started out as plain old, relatively harmless E. coli, but it picked up a whole bunch of genes that E. coli usually don't have, some of them quite nasty.

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Gene transfer between bacteria can greatly speed the rate at which an antibiotic-resistant gene spreads. Rather than having to evolve separately in each individual bacterial species, antibiotic resistance can, after having evolved once, be transferred to different species.

This type of gene acquisition by bacteria (called horizontal transfer to differentiate it from vertical transfer, in which the trait is passed down through descendents), occurs via three mechanisms:

i Transformation: The process whereby a bacterial cell picks up DNA from its environment and incorporates it into its own genome.

i Transduction: The process whereby genes are carried from one bacterium to another in a bacterial virus. Occasionally, before leaving the host cell, a virus particle that's being assembled accidentally gets filled with bacterial DNA instead of viral DNA. When that virus particle latches onto a new bacterium, it injects that bacterium with the foreign bacterial DNA, which may then be incorporated into the bacterium's genome.

i Conjugation: The process in which two bacteria join and DNA is passed from one to the next. This process is controlled by a small circle of DNA living within the bacterium, called a plasmid.

Plasmids, which are much bigger than the pieces of DNA usually involved in transformation and transduction, are especially important in the spread of antibiotic resistance. Through a single plasmid, a bacterium can become resistant to numerous antibiotics in one fell swoop, sometimes with tragic results: An outbreak of Shigella dysentery containing a plasmid coding for resistance to four antibiotics was responsible for over 10,000 deaths in Guatemala during the late 1960s.

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