What are the 3 different ways that bacteria become resistant to antibiotics?

In some cases, a type of bacteria will survive antibiotic treatment and multiply because it is intrinsically resistant. For example, although many types of bacteria have cell walls, some don’t. An antibiotic like penicillin that prevents cell-wall building can’t harm a bacterium that doesn’t build a cell wall in the first place.

Acquired Resistance

Bacteria can also acquire resistance. This happens when a type of bacteria changes in a way that protects it from the antibiotic. Bacteria can acquire resistance in two ways: either through a new genetic change that helps the bacterium survive, or by getting DNA from a bacterium that is already resistant.

Genetic Change

So how can a simple DNA change protect bacteria from antibiotics? Remember, DNA provides instructions to make proteins, so a change in DNA can cause a change in a protein. Sometimes this DNA change will affect the protein’s shape. If this happens at the place on the protein where an antibiotic acts, the antibiotic may no longer be able to recognize where it needs to do its job.

Changes like this can prevent an antibiotic from getting into the cell, or prevent the antibiotic from working once it’s inside. Once a change occurs, it can spread in a population of bacteria through processes like reproduction or DNA transfer.

DNA Transfer

Bacteria are very good at sharing genes, including genes for antibiotic resistance. They can share resistance genes that have been in the population, as well as new genetic changes that occur.

If you explored Agent Antibiotic, you saw a bacterium with an antibiotic resistance gene give a copy of that gene to another bacterium. This process is called lateral gene transfer.

There are other ways bacteria can transfer DNA. Did you know bacteria can get infected with a type of virus called a bacteriophage? As part of its life cycle, the bacteriophage packages DNA. When the bacterium dies, these packages of DNA (which sometimes include antibiotic resistance genes) are released and can be taken up and used by other bacteria.

Some resistance occurs without human action, as bacteria can produce and use antibiotics against other bacteria, leading to a low-level of natural selection for resistance to antibiotics. However, the current higher-levels of antibiotic-resistant bacteria are attributed to the overuse and abuse of antibiotics. In some countries and over the Internet, antibiotics can be purchased without a doctor's prescription. Patients sometimes take antibiotics unnecessarily, to treat viral illnesses like the common cold.

How do bacteria become resistant?
Some bacteria are naturally resistant to certain types of antibiotics. However, bacteria may also become resistant in two ways: 1) by a genetic mutation or 2) by acquiring resistance from another bacterium.

Mutations, rare spontaneous changes of the bacteria's genetic material, are thought to occur in about one in one million to one in ten million cells. Different genetic mutations yield different types of resistance. Some mutations enable the bacteria to produce potent chemicals (enzymes) that inactivate antibiotics, while other mutations eliminate the cell target that the antibiotic attacks. Still others close up the entry ports that allow antibiotics into the cell, and others manufacture pumping mechanisms that export the antibiotic back outside so it never reaches its target.

Bacteria can acquire antibiotic resistance genes from other bacteria in several ways. By undergoing a simple mating process called "conjugation," bacteria can transfer genetic material, including genes encoding resistance to antibiotics (found on plasmids and transposons) from one bacterium to another. Viruses are another mechanism for passing resistance traits between bacteria. The resistance traits from one bacterium are packaged into the head portion of the virus. The virus then injects the resistance traits into any new bacteria it attacks. Bacteria also have the ability to acquire naked, "free" DNA from their environment.

Any bacteria that acquire resistance genes, whether by spontaneous mutation or genetic exchange with other bacteria, have the ability to resist one or more antibiotics. Because bacteria can collect multiple resistance traits over time, they can become resistant to many different families of antibiotics.

Resistant bacteria spread via many routes. Different factors influence spread depending on the setting. Poor hygiene, poor sanitation, and poor infection control are three interconnected key factors contributing to the spread of resistant bacteria in health care facilities, in farms and in the community.

Bacteria know no boundaries and international traveling and trade help disseminate resistant bacteria across the world. Animals for food production are transported across borders and groceries are exported from most parts of the world, and the bacteria follow along. This contributes to the complexity of the antibiotic resistance problem and underpins the fact that it is a global issue. It does not matter where a resistant bacterium forms. If it is successful and increases in numbers it may quickly spread to other parts of the world in our globalized society.

Here follows an overview including an introductory video of some of the ways resistant bacteria can spread. For more information, see the selected resources at the bottom of the page, or read more in How did we end up here?

Person to person

Bacteria are everywhere, and we are exposed to them all the time. We all have our own unique bacterial “makeup”; some types of bacteria may be the same across populations while others differ, or the abundance of different types may vary. Bacteria can spread from one person to another through direct contacts between people. Transmission can also occur indirectly, for example when someone coughs. If a person contaminates a surface (such as a doorknob) with bacteria, these bacteria can be transferred to another person who touches the surface. That does not necessarily mean that this person will be infected or colonized by these bacteria. Good hand hygiene is important to limit the spread of pathogens and the risk of becoming a carrier of resistant bacteria. Still, even with good hygiene practices, bacteria are a normal part of our surroundings that we will be continuously exposed to.

Animals to humans and vice versa

Bacteria can spread from animals to humans, but also the other way around – from humans to animals. When animal pathogens become resistant to first line antibiotics, diseases become more difficult to treat, just as in humans. Many people come in close contact with animals in their daily life as we keep them as pets in our homes or raise animals for food. Wildlife encounters are also possible. Zoonotic diseases are infections that can be passed from animals to humans, either directly or by vectors such as ticks and mosquitoes.

Resistant bacteria can be common in livestock and there are several examples where farmers and their families carry the same resistant bacteria as their animals (for example). Likewise, livestock veterinarians are at risk of carrying livestock-associated resistant bacteria. The bacteria may then spread further in society.

Food

All animals have bacteria living in and on their bodies. In many animal farms, antibiotics are used to prevent and treat infections as well as for growth promotion. The animals on the farm can then become colonized with antibiotic resistant bacteria, that can spread among the animals. During slaughter or when processing the meat, these bacteria may also be transferred to the product. Crops that come in contact with animal manure may also be contaminated.

Eating food contaminated with bacteria may directly cause an infection, such as diarrhea caused by Salmonella, Campylobacter and enterohaemorrhagic E. coli (EHEC). Resistant bacterial strains, or genes encoding resistance, may also be transferred to the normal gut flora of the consumer without causing an infection. The resistant bacteria can potentially cause infections later on and spread to other people.

Resistant bacteria are frequently detected in chicken and meat and other produce. However, the exact impact of this is for human health is currently not known and may differ in different parts of the world. Some studies demonstrate similarities between the antibiotic resistance genes found in meat and those found in human pathogens, while other studies have not seen this connection, see for example.

Measures to reduce the risk of spreading antibiotic resistance via food includes the whole food chain such as disease prevention at farm, and appropriate hygiene from farm to fork. Proper cooking and handling of food helps to decrease the spread of infections as well as resistant bacteria.

Water

Bacteria can spread via drinking water or water supplies that are used for example for irrigation, washing cooking utensils or for hygienic purposes. Resistant bacteria have been found in many water sources such as drinking wells, rivers and effluents from wastewater treatment plants. Several bacterial diseases can spread via contaminated water, including typhoid fever and cholera. There are many ways resistant bacteria can end up in the water; release of untreated waste from animals and humans is one important source.

Spread within health care facilities

Health care facilities are hot spots for resistant bacteria since many sick people are in close vicinity of each other and antibiotic usage is high resulting in selection and spread of resistant strains. Poor hygiene practices may facilitate the spread of resistant bacteria via the hands or clothes of doctors, nurses and other health care staff, patients or visitors. Other risk factors include instruments that are not cleaned properly, improper cleaning of the facilities and insufficient sanitation. Crowded wards and few isolation rooms further facilitate spread. For more on this topic, see Health care-associated infections.

https://www.cdc.gov/infectioncontrol/projectfirstline/videos/HowGermsSpread-LowRes.mp4

Travel

International travelers spread resistant bacteria across the world. Any given day several million people will catch a flight, and if someone carries a resistant bacterium they will bring it along. Many studies have demonstrated that a large proportion of international travelers acquire resistant bacteria during visits in areas with a high prevalence of resistant bacteria (reviewed in). The risk is even higher for hospitalized patients, who are exposed to additional risk factors. Several hospital outbreaks have originated from patients transferred from another hospital with high prevalence of resistance.

Trade

Meat, fruits, vegetables, seeds, grain, and animals… the list of goods that are being imported and exported to and from different countries all over the world can be made long. Bacteria can potentially spread with any.

Selected Resources

ResourceDescriptionHow resistance happensInformation portal about how resistance develops, mechanisms and examples of how resistant bacteria spread. Also presents several infographics. US CDC.How does antibiotic resistance spread?Infographic about the spread of antibiotic resistance, developed by the European Centre for Disease Prevention and Control (ECDC), available in all EU/EEA official languages.What are the routes by which the infections are spread?Short animations on how bacteria spread. The first animation shows how infectious diseases can be spread by direct contact between animals in a pig herd while the three following videos the indirect mechanisms: the stable environment, through humans, and via vehicles. The last animation shows the general route for airborne transmission.

The text on the web pages is in Swedish, but you do not need to read the text to understand the context of the animation videos.

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