Mechanics of Resistance

Antibiotics kill or inhibit the growth of susceptible bacteria. Sometimes one of the bacteria survives because it has the ability to neutralize or evade the effect of the antibiotic; that one bacterium can then multiply and replace all the bacteria that were killed off. Exposure to antibiotics therefore provides selective pressure, which makes the surviving bacteria more likely to be resistant. Put another way, antibiotic resistance describes the ability of bacteria to survive or multiply, even in the presence of antibiotic levels that previously would have killed them or stopped their growth. This ability is encoded in genes (segments of DNA), which bacteria can pass onto future generations. 

A report published in June 2002 by the Alliance for the Prudent Use of Antibiotics, entitled "The Need To Improve Antimicrobial Use In Agriculture: Ecological And Human Health Consequences", describes in detail the mechanisms by which bacteria can become resistant to one or more antibiotics. 

When bacteria are initially exposed to an antibiotic, those most susceptible to an antibiotic will die quickly, leaving the hardier surviving bacteria to pass on the characteristics or genes that make them resistant. Bacteria are extremely numerous, and remarkably prolific. Under optimal conditions, a single bacterium can produce a billion offspring in a single day. Even if no bacteria initially have the ability to survive exposure to an antibiotic, random mutation of bacterial DNA generates a wide variety of genetic changes, some of which - sooner or later - will confer resistance. 

Mechanisms for resistance include: 

  • changes to the bacteria's outer membrane so that the antibiotic can no longer enter the cell;
  • biochemical pumps that remove the antibiotic from the bacteria before it can reach its target;
  • changes to the shape of the target so that the antibiotic can no longer affect it; and
  • enzymes that deactivate the antibiotic. 

The resistance problem is made worse by the fact that bacteria, unlike higher organisms, can transfer their DNA to bacteria that are not their offspring. They can even transfer DNA to bacteria of entirely different species. Most frequently, what is transferred is known as a plasmid - a small circle of DNA that is not part of the bacteria's regular DNA (which is found in its chromosomes). 

Even if bacteria that first develop resistance don't cause disease, they can transfer their resistance genes to other types of bacteria that do. And this bacterial "hanky panky" can occur pretty much anywhere. 

Plasmids can be exchanged among bacteria living in the broader environment, as well as by bacteria living in the human gut. One expert notes, "the exchange of genes is so pervasive that the entire bacterial world can be thought of as one huge multicellular organism in which the cells interchange their genes with ease.

"In short, the problem isn't just particular resistant germs that cause disease. It's resistance genes, in any type of bacteria. More bad news on plasmids: many of them carry several resistance genes simultaneously. A bacterium acquiring these plasmids can become a "superbug," able to withstand exposure to three, four, or more entire classes of antibiotics. These superbugs pose some of the toughest challenges to disease treatment today.