What the Heck is Antibiotic Resistance?

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What the Heck is Antibiotic Resistance?

Online article

By: John C. Brown

Date: January 2002

Source: University of Kansas, Department of Molecular Sciences. "What the Heck is Antibiotic Resistance?" 〈http://people.ku.edu/∼jbrown/resistance.htm〉 (accessed October 6, 2005).

About the Author: John C. Brown is an immunologist and professor of microbiology at the University of Kansas. Brown's current research involves the molecular and genetic mechanisms involved in the disease systemic lupus erythematosus.

INTRODUCTION

The ability to adapt is a crucial aspect to the survival of bacteria. Bacteria can adapt to challenges by altering their structure and metabolism. Some of these alterations occur only as long as the challenge is imposed. Other adaptations require changes in the genetic material of the bacteria that can be passed on to succeeding generations. Such heritable changes are the basis of the emergence of bacterial resistance to antibiotics.

The first known antibiotic, penicillin, was discovered in 1929. Since then many more naturally produced antibiotics have been discovered or chemically synthesized. When these agents were first used, the prospect of complete control of troublesome bacteria was readily envisioned. However, within a few decades of the introduction of penicillin, bacterial resistance to the antibiotic appeared.

Once resistance appears, its spread can be rapid. For example, by the mid 1990s, almost 80 percent of all strains of Staphylococcus aureus had acquired resistance to penicillin.

Bacterial antibiotic resistance can occur in two ways. One is inherent (or natural) resistance. Gramnegative bacteria such as Escherichia coli are often naturally resistant to penicillin, for example. This is because these bacteria are surrounded by two membranes. The outer membrane makes it more difficult for an antibiotic like penicillin to reach its target inside the cell. In addition, enzymes located in the gap between the outer and inner membranes can dissolve some antibiotics as they reach the gap. Sometimes, bacterial resistance to an antibacterial agent arises when a change in the outer membrane restricts the inward movement of the antibiotic. Such a change represents adaptation.

Resistance can also be acquired, and is almost always due to a change in the genetic make-up of the bacterial genome. The genomic change can occur because of a random mutation or as a directed response by the bacteria to the selective pressure imposed by the antibacterial agent. Once the genetic alteration that confers resistance is present, it can be passed on to subsequent generations. In this way, the resistance can quickly spread as succeeding generations of bacteria develop.

PRIMARY SOURCE

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SIGNIFICANCE

Acquired adaptation of bacteria to many antibiotics has become a problem since the early 1990s. For example, many hospitals now must cope with the presence of methicillin-resistant Staphylococcus aureus (MRSA), which displays resistance to almost all currently used antibiotics. Dealing with infections caused by MRSA and other resistant organisms requires increased hospital staff hours, increased supplies, and can restrict the availability of hospital beds when cohorting (grouping together patients with the same disease) or isolation is necessary.

The few antibiotics to which antibiotic-resistant bacteria do respond tend to be expensive, with few options for delivery. For example, the drug meropenum is sometimes prescribed for persons with pneumonia, meningitis, or serious skin infections that are caused by organisms that are resistant to common antibiotics. Meropenum can be delivered by intravenous injection or infusion only, and is two to three times more expensive than the commonly prescribed antibiotics for these conditions.

Additionally, disease-causing organisms can sometimes adapt so that they are able grow and multiply on solid surfaces. This mode of growth is called a biofilm. A biofilm environment induces many changes in growing bacteria, many involving the expression of previously unexpressed genes and deactivation of actively expressing genes. The structure of the biofilm and these genetic changes often make the bacteria extraordinarily resistant to many antibiotics. Biofilms sometimes occur on some hospital surfaces, and in implanted devices such as artificial joints and long-term intravenous access catheters.

Complicating the picture, the pattern of gene expression may not be uniform throughout the biofilm. Evidence from studies where intact and undisturbed biofilms have been studied has shown that the bacteria living near the top of the biofilm, and so closer to the outside environment, are very different from their counterparts located deeper in the biofilm. This arrangement functions to make the bacterial population very hardy when confronted with antibiotics and other threats to their survival.