“A post-antibiotic era means, in effect, an end to modern medicine as we know it. Things as common as strep throat or a child’s scratched knee could once again kill. Some sophisticated interventions, like hip replacements, organ transplants, cancer chemotherapy, and care of preterm infants, would become far more difficult or even too dangerous to undertake.”

The former Director-General of the World Health Organization, Dr. Margaret Chan, stated this in 2012. She was referring to the growing crisis of antibiotic resistance, which is slowly resulting in the loss of treatment options for certain bacterial infections that are currently treatable. The unsettling fact is that the Centers for Disease Control and Prevention (CDC) estimates that approximately 2 million people per year develop an antibiotic-resistant infection and at least 23,000 die as a result.

This growing crisis is due to a number of factors including overuse of antibiotics, large-scale agricultural use of antibiotics and the lack of new antibiotics to overcome microbial resistance to current options. Improper prescribing of antibiotics is also a significant factor that contributes to the problem. Shockingly, the CDC estimates that at least 47 million antibiotic prescriptions per year are unnecessary.

What are antibiotics?

Antibiotics are compounds that kill bacteria.

Our bodies contain trillions of harmless bacteria that co-exist in our bodies, many of which contribute to our health and are referred to as the “microbiome”. However, there are many types of bacteria that cause infections and are deleterious to our health. Some of these bacteria include those that cause pneumonia, strep throat, tuberculosis and gonorrhea. These harmful bacterial infections are largely treated with antibiotics, which were pioneered by the discovery of penicillin in 1928 by Alexander Fleming.

Antibiotics can work by inhibiting cell wall synthesis. This ruptures bacterial cell walls.
Antibiotics can work by inhibiting cell wall synthesis. This ruptures bacterial cell walls.

How do antibiotics work?

Antibiotics work by selectively killing bacterial cells while avoiding the normal cells of our organs. To do this, they target certain structural parts of bacteria or cellular processes that are unique to bacteria.

Unlike the cells in our bodies, which are surrounded by a cell membrane, bacterial cells have an additional outer layer, a more rigid cell wall. The bacterial cell wall is composed of a protein called peptidoglycan and because of its uniqueness to bacterial cells, it is one of the major targets of antibiotics.

There are two broad types of bacterial cells, termed gram-positive and gram-negative, each of which have slightly different cell wall compositions. Gram-positive bacterial cell walls are thicker than those of gram-negative bacteria. However, gram-negative bacteria also possess an outer membrane that can exclude particular molecules, including antibiotics, from entering the bacterial cell.

Bacterium cell model.
Bacterium cell model.

Some antibiotics, like penicillin, act by binding to molecules called penicillin-binding proteins that are important for synthesizing and building peptidoglycan for the cell wall. The binding of penicillin to penicillin-binding proteins inhibits the function of these proteins, preventing formation of the peptidoglycan structure. This results in the death of the bacterial cell. Antibiotics that act in this way are termed β-lactams because of their chemical structure.

Other types of antibiotics act by disrupting crucial bacterial processes. Like human cells, bacterial cells synthesize new cellular proteins in a process called translation that utilizes organelles called ribosomes. However, bacterial and human ribosomes are different enough that certain antibiotics can target bacterial ribosome components while disregarding the ribosomes of human cells. Antibiotics called aminoglycosides, like streptomycin, enter the bacterial cell through pores in the outer membrane and target the bacterial ribosome, disrupting protein translation.

What is antibiotic resistance?

Bacteria become resistant to antibiotics when the targets of antibiotics become less critical for survival. In other words, if bacteria can utilize secondary pathways to overcome sensitivity to antibiotics, they become resistant. For example, as a β-lactam antibiotic, penicillin interferes with the formation of bacterial cell walls by binding to penicillin-binding proteins and preventing their activity. To develop resistance against penicillin, a bacterium must develop an alternative mechanism to circumvent the activity of penicillin-binding proteins.

This can be achieved in multiple ways by different types of bacteria. Gram-negative bacteria can produce mutant penicillin-binding proteins that are modified to bind penicillin less well. Gram-positive bacteria can make enzymes called β-lactamases that break down β-lactam antibiotics, rendering them inactive and preventing them from being effective.

In addition to modifying the targets of antibiotics, bacteria can also develop antibiotic resistance by preventing antibiotics from entering the cell or by increasing the activity of efflux pumps that ship antibiotics back out.

For example, to kill bacteria, aminoglycosides enter bacterial cells through pores in the outer membranes of gram-negative bacteria. Bacteria can develop resistance against aminoglycosides by decreasing the number of pores on their outer membrane, making it more difficult for aminoglycosides to enter and have an effect. Additionally, bacterial cells also have efflux pumps that are able to pump antibiotic molecules out of the bacterial cell, preventing them from having an effect.

The antibiotic resistant bacteria.
The antibiotic resistant bacteria.

How do bacteria become resistant to antibiotics?

Antibiotic resistance is in a way a form of evolution via natural selection. The overuse of antibiotics selects for bacteria that are resistant, creating larger populations of resistant bacteria.

An antibiotic regimen will kill all bacteria that are sensitive to a given antibiotic. Some bacteria may have a random genetic mutation that confers resistance and allows them to escape the effects of the antibiotic, demonstrating resistance. This mutation may change the shape of penicillin-binding proteins or increase the production of β-lactamases.

Randomly resistant bacteria will survive the antibiotic regimen and continue to multiply, generating many more bacteria that are similarly resistant to that antibiotic. Continual treatment of a bacterial population with the same antibiotic will continue to kill the sensitive population but leave the resistant population to thrive. In fact, this process actually removes competition, making it more likely that the resistant bacteria will continue to grow, survive and multiply.

When an antibiotic resistant bacterium multiplies, it produces more bacteria that are resistant to the same antibiotic. Antibiotic resistant bacteria can also transfer genetic material containing resistance genes to each other in a process called horizontal gene transfer. In this way, they can produce resistant populations without having to multiply.

What can I do about antibiotic resistance?

In practice, the more an antibiotic is used, the greater the chances that resistance will occur. In fact, overuse of antibiotics is one of the most common causes of antibiotic resistance. Additionally, the fact that very few new antibiotics have been developed in recent years remains a large concern. Following the discovery of penicillin, there was an antibiotic boom. However, very few new antibiotics have been developed since the early 2000s, leaving us with fewer and fewer options as more bacterial populations develop resistance to existing antibiotics.

Therefore, limiting the use of antibiotics for when they are truly needed and protecting ourselves and those around us against germs of all kinds are some of the major things we can do to combat this crisis.

Although we are all at risk for developing antibiotic-resistant infections, some are more at risk than others. At risk individuals include young children, the elderly and others with weakened immune systems. One of the most simple things we can do is consistently wash our hands. We might reach for the antibacterial soap thinking that it will “work better”, but in fact, the Food and Drug Administration (FDA) has found that there is not enough proof to demonstrate that antibacterial soap is more effective at preventing infections than regular soap.

Another area where we may be unknowingly exposed to antibiotics is through the meat we eat. According to the US Department of Agriculture (USDA), “The terms ‘no antibiotics added’ may be used on labels for meat or poultry products if sufficient documentation is provided by the producer to the Agency demonstrating that the animals were raised without antibiotics.” 

Although an animal must be free of antibiotics before slaughter, without a label to indicate otherwise, it may have been treated with low doses of antibiotics to improve growth and reduce disease. Any long-term use of antibiotics can increase the chances that antibiotic resistance may occur and there is no way to determine whether the meat you buy at the store does not contain antibiotic-resistance bacteria. Therefore, it is critical that we practice food safety at home and consider buying meat from responsibly labeled sources if possible and available. Look for no antibiotics added” labeled meat at your local grocery store or farmer’s market.

Remember that the best thing we can do to combat any germs is wash our hands – and maybe think twice about overusing the antibacterial soap.

For more information, check out the CDC’s recommendations for protecting yourself and your family against antibiotic resistance here.