What Is Antibiotic Resistance?

iStock
iStock

The news is full of terms like "superbug," "post-antibiotic era," and an alphabet soup of abbreviations including NDM-1, MCR-1 (both antibiotic resistance genes), MRSA (a type of antibiotic-resistant bacteria), and others. These all refer to various aspects of antibiotic resistance—the ability of bacteria to out-maneuver the drugs which are supposed to kill them and stop an infection.

Now, there is concern that we could move back into a situation like that which existed in the early 20th century—a post-antibiotic era. Mental Floss spoke to Meghan Davis, a veterinarian and assistant professor of epidemiology at Johns Hopkins University, about some of the potential outcomes of losing antibiotics. "We have generations of recorded history that identify the risks to human society from infectious diseases that we are unable to treat or prevent," Davis warns.

WHY IS ANTIBIOTIC RESISTANCE DANGEROUS?

If an individual becomes ill due to a bacterial infection, they typically see their physician for treatment. But in the years before antibiotics were discovered, people frequently died from scenarios we find difficult to fathom, including mere cuts or scratches that led to untreatable infections. Ear infections or urinary tract infections could lead to sepsis (bacteria in the blood). Arms or legs were surgically removed before an infected wound could lead to death.

When antibiotics were discovered, it's no surprise they were referred to as a "magic bullet" (or Zauberkugel in German, as conceived by medical pioneer Paul Ehrlich [PDF]). The drugs could wipe out an infection but not harm the host. They allowed people to recover from even the most serious of infections, and heralded a new era in medicine where people no longer feared bacteria.

Davis says the existence of antibiotics themselves has changed how we use medicine. Many medical procedures now rely on antibiotics to treat infections that may result from the intervention. "What is different about a post-antibiotic modern world is that we have established new patterns of behavior and medical norms that rely on the success of antimicrobial treatments," she says. "Imagine transplant or other major surgeries without the ability to control opportunistic infections with antibiotics. Loss of antibiotics would challenge many of our medical innovations."

WHERE DOES ANTIBIOTIC RESISTANCE COME FROM?

One reason antibiotic resistance is difficult to control is that our antibiotics are derivatives of natural products. Our first antibiotic, penicillin, came from a common mold. Fungi, bacteria, parasites, and viruses all produce products to protect themselves as they battle each other in their microbial environments. We've taken advantage of the fruits of millions of years' worth of these invisible wars to harness antibiotics for our use. (This is also why we can find antibiotic resistance genes even in ancient bacteria that have never seen modern antibiotic drugs—because we've exploited the chemicals they use to protect themselves).

These microbes have evolved ways to evade their enemies—antibiotic resistance genes. Sometimes the products of these genes will render the antibiotic useless by chopping it into pieces or pumping it out of the bacterial cell. Importantly, these resistance genes can be swapped among different bacterial species like playing cards. Sometimes the genes will be useless because the bacteria aren't being exposed to a particular drug, but sometimes they'll be dealt an ace and survive while others die from antibiotic exposure.

And many of these resistance genes are already out there in the bacterial populations. Imagine just one in a million bacterial cells that are growing in a human gut have a resistance gene already in their DNA. When a person takes a dose of antibiotics, all the susceptible bacteria will die off—but that one-in-a-million bacterium that can withstand the antibiotic suddenly has a lot of room to replicate, and the population of bacteria carrying that resistance gene will dramatically increase.

If the person then transfers those resistant gut bacteria to others, resistance can spread as well. This is why it's important to keep control over antibiotic use in all populations—because someone else's use of the drugs can potentially make your own bacteria resistant to antibiotics. This is also why hand washing is important: You can unknowingly pick up new bacteria all the time from other people, animals, or surfaces. Washing your hands will send most of these passenger bacteria down the sink drain, instead of allowing them to live on your body.

WHAT CAN YOU DO ABOUT IT?

Most importantly, never ask for antibiotics from your doctor; if you have a bacterial infection that can be treated by antibiotics, your doctor will prescribe them. Many illnesses are due to viruses (such as the common cold), but antibiotics only work against bacteria. It is useless to take antibiotics for a virus, and doing so will only breed resistance in the other bacteria living in your body, which can predispose you or others in your household and community to developing an antibiotic-resistant infection. Remember, those resistant bacteria can linger in your body—in your gut, on your skin, in your mouth and elsewhere, and can swap resistance genes from the mostly harmless bacteria you live with to the nasty pathogens you may encounter, further spreading resistance in the population.

Antibiotics are also used in animals, including livestock. Purchasing meat that is labeled "raised without antibiotics" will reduce your chance of acquiring antibiotic-resistant bacteria that are generated on the farm and can be spread via meat products.

Davis notes clients often requested antibiotics for their pets as well, even when it was an issue that did not require them. She explained to them why antibiotics were not necessary. She counsels, "Individuals can partner with their physician and veterinarian to promote good antimicrobial stewardship. Use of antibiotics carries risks, and these risks are related both to side effects and to promotion of resistance. Therefore, decisions to use antibiotics should be treated with caution and deliberation."

Keep Your Cat Busy With a Board Game That Doubles as a Scratch Pad

Cheerble
Cheerble

No matter how much you love playing with your cat, waving a feather toy in front of its face can get monotonous after a while (for the both of you). To shake up playtime, the Cheerble three-in-one board game looks to provide your feline housemate with hours of hands-free entertainment.

Cheerble's board game, which is currently raising money on Kickstarter, is designed to keep even the most restless cats stimulated. The first component of the game is the electronic Cheerble ball, which rolls on its own when your cat touches it with their paw or nose—no remote control required. And on days when your cat is especially energetic, you can adjust the ball's settings to roll and bounce in a way that matches their stamina.

Cheerable cat toy on Kickstarter.
Cheerble

The Cheerble balls are meant to pair with the Cheerble game board, which consists of a box that has plenty of room for balls to roll around. The board is also covered on one side with a platform that has holes big enough for your cat to fit their paws through, so they can hunt the balls like a game of Whack-a-Mole. And if your cat ever loses interest in chasing the ball, the board also includes a built-in scratch pad and fluffy wand toy to slap around. A simplified version of the board game includes the scratch pad without the wand or hole maze, so you can tailor your purchase for your cat's interests.

Cheerble cat board game.
Cheerble

Since launching its campaign on Kickstarter on April 23, Cheerble has raised over $128,000, already blowing past its initial goal of $6416. You can back the Kickstarter today to claim a Cheerble product, with $32 getting you a ball and $58 getting you the board game. You can make your pledge here, with shipping estimated for July 2020.

At Mental Floss, we only write about the products we love and want to share with our readers, so all products are chosen independently by our editors. Mental Floss has affiliate relationships with certain retailers and may receive a percentage of any sale made from the links on this page. Prices and availability are accurate as of the time of publication.

How Are Vaccines Made?

Eugeneonline/iStock via Getty Images
Eugeneonline/iStock via Getty Images

Vaccines have long been hailed as one of our greatest public health achievements. They can be made to protect us from infections with either viral or bacterial microbes. Measles and smallpox, for example, are viruses; Streptococcus pneumoniae is a bacterium that causes a range of diseases, including pneumonia, ear and sinus infections, and meningitis. Hundreds of millions of illnesses and deaths have been prevented due to vaccines that eradicated smallpox and significantly reduced polio and measles infections. However, some misunderstanding remains regarding how vaccines are made, and why some scary-sounding ingredients [PDF] are included in the manufacturing process.

The production of our vaccines has evolved a lot since the early days, when vaccination was potentially dangerous. Inoculating an individual with ground-up smallpox scabs usually led to a mild infection (called "variolation"), and protected them from acquiring the disease the "regular" way (via the air). But there was always a chance the infection could still be severe. When Edward Jenner introduced the first true vaccination with cowpox, protection from smallpox became safer, but there were still issues: The cowpox material could be contaminated with other germs, and sometimes was transmitted from one vaccinated person to another, leading to the inadvertent spread of blood-borne pathogens. We’ve come far in the last 200 years.

There are different kinds of vaccines, and each requires different processes to move from the laboratory to your physician's office. The key to all of them is production of one or more antigens—the portion of the microbe that triggers a host immune response.

Live Attenuated Vaccines and Dead, "Inactivated" Vaccines

There are several methods to produce antigens. One common technique is to grow a virus in a cell culture. Typically grown in large vats called bioreactors, living cells are inoculated with a virus and placed in a liquid growth medium that contains nutrients—proteins, amino acids, carbohydrates, essential minerals—that help the virus grow in the cells, producing thousands of copies of itself in each infected cell. At this stage the virus is also getting its own dose of protective medicine: antibiotics like neomycin or polymyxin B, which prevent bacterial and fungal contamination that could kill the cells serving as hosts for the virus.

Once a virus completes its life cycle in the host cell, the viruses are purified by separating them from the host cells and growth media, which are discarded. This is often done using several types of filters; the viruses are small and can pass through holes in the filter that trap larger host cells and cell debris.

This is how "live attenuated vaccines" are created. These vaccines contain viruses that have been modified so that they are no longer harmful to humans. Some of them are grown for many generations in cells that aren't human, such as chicken cells, so that they have mutated to no longer cause harm to humans. Others, like the influenza nasal mist, were grown at low temperatures until they lost the ability to replicate in the warmer temperatures of the lungs. Many of these vaccines you were probably given as a child: measles, mumps, rubella, and chickenpox.

Live attenuated vaccines replicate briefly in the body, triggering a strong—and long-lasting—response from your immune system. Because your immune system kicks into high gear at what it perceives to be a major threat, you need fewer doses of the vaccine for protection against these diseases. And unlike the harmful form of the virus, it is extremely unlikely (because they only replicate at low levels) that these vaccines will cause the host to develop the actual disease, or to spread it to other contacts. One exception is the live polio vaccine, which could spread to others and, extremely rarely, caused polio disease (approximately one case of polio from 3 million doses of the virus). For this reason, the live polio virus was discontinued in the United States in 2000.

Scientists use the same growth technique for "killed" or "inactivated" vaccines, but they add an extra step: viral death. Inactivated viruses are killed, typically via heat treatment or use of a chemical such as formaldehyde, which modifies the virus's proteins and nucleic acids and renders the virus unable to replicate. Inactivated vaccines include Hepatitis A, the injected polio virus, and the flu shot.

A dead virus can't replicate in your body, obviously. This means that the immune response to inactivated vaccines isn't as robust as it is with live attenuated vaccines; replication by the live viruses alerts many types of your immune cells of a potential invader, while killed vaccines primarily alert only one part of your immune system (your B cells, which produce antibodies). That's why you need more doses to achieve and maintain immunity.

While live attenuated vaccines were the primary way to make vaccines until the 1960s, concerns about potential safety issues, and the difficulty of making them, mean that few are attempting to develop new live attenuated vaccines today.

Combination, Bacterial, and Genetically Engineered Vaccines

Other vaccines aren't made of whole organisms at all, but rather bits and pieces of a microbe. The combination vaccine that protects against diphtheria, pertussis, and tetanus—all at once—is one example. This vaccine is called the DTaP for children, and Tdap for adults. It contains toxins (the proteins that cause disease) from diphtheria, pertussis, and tetanus bacteria that have been inactivated by chemicals. (The toxins are called "toxoids" once inactivated.) This protects the host—a.k.a. you, potentially—from developing clinical diphtheria and tetanus disease, even if you are exposed to the microorganisms. (Some viruses have toxins—Ebola appears to, for example—but they're not the key antigens, so they're not used for our current vaccines.)

As they do when developing live attenuated or inactivated vaccines, scientists who create these bacterial vaccines need some target bacteria to culture. But because the bacteria don't need a host cell to grow, they can be produced in simple nutrient broths by vaccine manufacturers. The toxins are then separated from the rest of the bacteria and growth media and inactivated for use as vaccines.

Similarly, some vaccines contain just a few antigens from a bacterial species. Vaccines for Streptococcus pneumoniae, Haemophilus influenzae type B, and Neisseria meningitidis all use sugars that are found on the outer part of the bacteria as antigens. These sugars are purified from the bacteria and then bound to another protein to enhance the immune response. The protein helps to recruit T cells in addition to B cells and create a more robust reaction.

Finally, we can also use genetic engineering to produce vaccines. We do this for Hepatitis B, a virus that can cause severe liver disease and liver cancer. The vaccine for it consists of a single antigen: the hepatitis B surface antigen, which is a protein on the outside of the virus. The gene that makes this antigen is inserted into yeast cells; these cells can then be grown in a medium similar to bacteria and without the need for cell culture. The hepatitis B surface antigen is then separated from the yeast and serves as the primary vaccine component.

Other Ingredients in Vaccines (and Why They're There)

Once you have the live or killed viruses, or purified antigens, sometimes chemicals need to be added to protect the vaccine or to make it work better. Adjuvants, such as aluminum salts, are a common additive; they help enhance the immune response to some antigens by keeping the antigen in contact with the cells of the immune system for a longer period of time. Vaccines for DTaP/Tdap, meningitis, pneumococcus, and hepatitis B all use aluminum salts as an adjuvant.

Other chemicals may be added as stabilizers, to help keep the vaccine working effectively even in extreme conditions (such as hot temperatures). Stabilizers can include sugars or monosodium glutamate (MSG). Preservatives can be added to prevent microbial growth in the finished product.

For many years, the most common preservative was a compound called thimerosal, which is 50 percent ethylmercury by weight. Ethylmercury doesn't stick around; your body quickly eliminates it via the gut and feces. (This is different from methylmercury, which accumulates in fish and can, at high doses, cause long-lasting damage in humans.) In 2001, thimerosal was removed from the vaccines given in childhood due to consumer concerns, but many studies have demonstrated its safety.

Finally, the vaccine is divided into vials for shipping to physicians, hospitals, public health departments, and some pharmacies. These can be single-dose or multi-dose vials, which can be used for multiple patients as long as they're prepared and stored away from patient treatment areas. Preservatives are important for multi-dose vials: bacteria and fungi are very opportunistic, and multiple uses increase the potential for contamination of the vaccine. This is why thimerosal is still used in some multi-dose influenza vaccines.

Though some of the vaccine ingredients sound worrisome, most of these chemicals are removed during multiple purification steps, and those that remain (such as adjuvants) are necessary for the vaccine's effectiveness, are present in very low levels, and have an excellent track record of safety.