Bugs Fighting Back: Basics of Bacterial Resistance

Bugs Fighting Back
Basics of Bacterial Resistance

How Bacteria Become Resistant

Once it was thought that antibiotics would help us wipe out forever the diseases caused by bacteria. But the bacteria have fought back by developing resistance to many antibiotics. Bacterial resistance to antibiotics can be acquired in four ways:

Through a spontaneous change in the bacterium's DNA: Changes like this are called mutations. Mutations happen at random in all living things, and they can result in all kinds of changes in the bacterium. Antibiotic resistance is just one of many changes that can result from a random mutation.

Transformation: This happens when one bacterium takes up some DNA from the chromosomes of another bacterium.

Plasmid exchange: Antibiotic resistance can be coded for in the DNA found in a small circle known as a plasmid in a bacterium. The plasmids can randomly pass between bacteria (usually touching).

Sharing of mutations, some of which control resistance to antibiotics. Two examples are:

Plasmid transfer between different kinds of bacteria. This can happen between similar bacteria and between very dissimilar bacteria.

Gene cassettes are a small group of genes that can be added to a bacterium's chromosomes. The bacteria can then accept a variety of gene cassettes that give the bacterium resistance to a variety of antibiotics. The cassettes also can confirm resistance against disinfectants and pollutants.

The acquired genetically based resistance is permanent and inheritable through the reproductive process of bacteria, called fission.

Some bacteria produce their own antibiotics to protect themselves against other microorganisms. Of course, a bacterium will be resistant to its own antibiotic! But sometimes the DNA that gives that bacterium resistance to its own antibiotic can be transferred to a bacterium of another species. Then that other bacterium could be resistant to the first bacterium's antibiotic! Scientists think, but haven't proved, that the genes for resistance in this case have been transferred between bacteria of different species through plasmid or cassette transfer. Laboratory analysis of commercial antibiotic preparations has shown that they contain DNA from antibiotic-producing organisms. The DNA includes the antibiotic-resistance gene sequence.

Genetic transfer may be induced by the bacteria involved, that is the source and the destination bacteria. One model suggests that when a DNA resistance plasmid released by one bacterium is accepted by a different species of bacterium, the recipient may be stimulated to release its own plasmid. The process is known as retrotransfer.

Resistant genes occur not only in bacteria that carry disease, but also in commensal bacteria (those living within the same environment—soil, water, digestive tract—benefiting from each other). Eating meat or milk from animals that have been exposed to antibiotics, or plants that have been exposed to pesticides, brings the antibiotic and/or resistant bacteria in contact with bacteria in your digestive tract. The interaction between bacteria can then allow for transfer of genes for antibiotic resistance to the bacteria in your intestines.
How Resistance Works
Some mechanisms for resistance include:

Changing the target molecule: For example, if the antibiotic attacks a certain enzyme in a bacterium, the bacterium can adapt by using a different enzyme to accomplish the same function.

Enzymatically inactivating or decomposing the antibiotic.

Sequestering (storing) the drug by creating alternative pathways within the bacterium.

Preventing the drug from entering the bacterium.

Pumping out the antibiotic as quickly as it enters the bacterium.

Recommended Actions for Consumers and Physicians to Limit Resistance
(from Levy, S.B. Scientific American, March 1998; p 53.)
Consumers:

Do not demand antibiotics.

Never use antibiotics unless they are prescribed by your doctor.

When given antibiotics, take them exactly as prescribed and complete the full course of treatment: continue taking the antibiotic even after you start to feel well, and do not hoard pills for later use.

Wash fruits and vegetables thoroughly; avoid raw eggs and undercooked meat, especially in ground form.

Avoid antibacterial soaps and other products unless you are caring for a sick person whose defenses are weakened.

Physicians (Who knows? You might be a doctor someday!):

Wash hands thoroughly between patient visits.

Do not give in to patients' demands for unneeded antibiotics.

When possible, prescribe antibiotics that target only a narrow range of bacteria.

Isolate hospital patients with multidrug-resistant infections.

Familiarize yourself with local data on antibiotic resistance.

For Further Reading

Nordenberg, Tamar. “Miracle Drugs vs. Superbugs,” FDA Consumer, November/December 1998; pp 22-25.

Radetsky, Peter “Last Days of the Wonder Drugs,” Discover, November 1998; pp 76-85.

Levy, S.B. “The Challenge of Antibiotic Resistance,” Scientific American, March 1998; pp. 46-53.

Miller, R.V. “Bacterial Gene Swapping in Nature,” Scientific American, January 1998.

For more information, at other Web sites...

The Alliance for the Prudent Use of Antibiotics (APUA) — official site with information for patients and health care professionals.
The Rise of Antibiotic-Resistant Infections — from FDA Consumer, September 1995, published by the U.S. Food and Drug Administration.

Back to:
Antibiotics in Action Directory | Site Map | Pharmaceutical Achievers Home

References

Devitt, Terry, ed. Microbes: What Doesn't Kill them Makes them Stronger, The Why Files, University of Wisconsin, May 1997.

Hawkey, Peter M. “The Origins and Molecular Basis of Antibiotic Resistance,” British Medical Journal, September 5, 1998, pp. 657-660.

Levy, S.B. "The Challenge of Antibiotic Resistance," Scientific American, March 1998; pp. 46-53.

Copyright ©2002 The Chemical Heritage Foundation