Have you ever had a bad infection that just didn’t seem to go away? Or a runny nose that keeps coming back? You may have been dealing with bacteria that are tolerant of antibiotics, although not yet resistant to them.

Antibiotic resistance is a huge problem, contributing to nearly 1.27 million deaths worldwide in 2019. But antibiotic tolerance is a hidden threat that researchers have only recently begun to explore.

Antibiotic tolerance occurs when bacteria can survive for a long time after exposure to an antibiotic. While antibiotic-resistant bacteria thrive even in the presence of an antibiotic, tolerant bacteria are often found in a dormant state, neither growing nor dying but coexisting with the antibiotic so they can “wake up” once the stress is gone.

Tolerance has been linked to the spread of antibiotic resistance.

I am a microbiologist who studies antibiotic tolerance, seeking to uncover what triggers tolerant bacteria to enter a protective, dormant hibernation. By understanding why bacteria are so hardy, researchers hope to develop ways to avoid the spread of this ability.

The exact mechanism that differentiates tolerance from resistance was unclear. But one possible answer may lie in a process that has been ignored for decades: how bacteria create their energy.

Cholera and antibiotics

Many antibiotics are designed to penetrate the outer defenses of bacteria like a cannonball through a stone fortress. Resistant bacteria are immune to the cannonball because they can destroy them before they destroy their outer wall or alter their walls to be able to withstand the impact.

Tolerant bacteria can remove their entire wall and completely avoid damage. No wall, no target for a cannonball to smash through. If the threat disappears before long, the bacteria can rebuild their wall to protect it from other environmental dangers and resume normal functions.

However, it remains unknown how bacteria know the antibiotic threat is gone, and what exactly triggers their reawakening.

My colleagues and I in Dorr’s lab at Cornell University are trying to understand the activation and reawakening processes in the tolerant bacteria responsible for cholera, Vibrio cholera. Vibrio Resistance to various types of antibiotics is rapidly developing, and doctors are concerned.

As of 2010, Vibrio It is already resistant to 36 different antibiotics, and that number is expected to continue to rise.

to study how Vibrio develops resistance, we chose a strain that is tolerant to a class of antibiotics called beta-lactams. Beta-lactams are the cannonball sent to destroy the fortress of bacteria, and Vibrio It adapts by activating two genes that temporarily remove the cell wall. I witnessed this phenomenon with a microscope.

After removing the cell wall, the bacteria activate more genes that turn them into fragile balls that can survive the effects of the antibiotic. Once the antibiotic has been removed or hydrolyzed, Vibrio It returns to its normal penis shape and continues to grow.

border frame=”0″allow=”accelerometer; auto start; Clipboard write. gyroscope encoded media; picture in picture; web sharing “allowfullscreen>”.

In people, this tolerance process is seen when a doctor prescribes an antibiotic, usually doxycycline, to a patient with cholera. The antibiotic seems to stop the infection temporarily. But then the symptoms start to reappear because the antibiotics didn’t completely clear out the bacteria in the first place.

border frame=”0″allow=”accelerometer; auto start; Clipboard write. gyroscope encoded media; picture in picture; web sharing “allowfullscreen>”.

Being able to return to normal and grow after the antibiotic wears off is key to survival. expose Vibrio on an antibiotic long enough to finally kill him. But standard antibiotic treatment is often not long enough to get rid of all bacteria even in their fragile state.

However, taking the drug for a long time can harm healthy bacteria and cells, causing more discomfort and illness. In addition, misuse and prolonged exposure to antibiotics can increase the chances of resistance to other bacteria in the body.

Other bacteria develop tolerance

Vibrio They are not the only species that show tolerance. In fact, researchers recently identified several infectious bacteria that have evolved a tolerance. A family of bacteria called Enterobacteriaceae, which includes major foodborne pathogens salmonellaAnd Shigella And coliare just a few of the many types of bacteria that are able to tolerate antibiotics.

Since each bacterium is unique, so does the way one develops endurance. Some bacteria, eg Vibrio, erasing their cell walls. Others can change their energy sources, increase their mobility or simply inject an antibiotic.

I recently discovered that bacteria’s metabolism, or the way they break down “food” to produce energy, may play an important role in their endurance. Various structures within bacteria, including their outer wall, are made up of specific building blocks such as proteins.

Stopping the bacteria’s ability to make these pieces weakens their wall, making it more likely that they will be exposed to damage from the external environment before they can destroy the wall.

Tolerance and resistance are connected

Although there is a great deal of research on how bacteria develop tolerance, a key part of the puzzle that has been neglected is how tolerance leads to resistance.

In 2016, researchers discovered how to make bacteria tolerant in the lab. After repeated exposure to different antibiotics, coli The cells were able to adapt and survive. DNA, the genetic material that contains instructions for cell function, is a fragile molecule.

When DNA is rapidly damaged by stress, such as from exposure to antibiotics, the cell’s repair mechanisms tend to cause mutations that can create resistance and tolerance.

because coli Similar to many different types of bacteria, these researchers’ findings revealed that, ironically, basically any bacteria can develop a tolerance if pushed to their limits by antibiotics intended to kill them.

A recent major discovery was that the longer a bacterium persists, the more likely it is that it will develop mutations that lead to resistance. Tolerance allows bacteria to develop a resistant mutation that reduces their chances of being killed during antibiotic treatment. This is particularly important for bacterial communities that often appear in biofilms that tend to cover high-touch surfaces in hospitals.

Biofilms are sticky layers of bacteria that secrete a protective gel that makes antibiotic treatment difficult and DNA sharing between microbes easy. They can induce bacteria to develop resistance. These conditions are thought to mimic what can happen during antibiotic-treated infections, where many bacteria live side by side and share DNA.

The researchers are calling for more research into antibiotic tolerance in hopes that it will lead to more powerful treatments in both infectious diseases and cancers. And there is cause for optimism. In one promising development, a rat study found that reducing tolerance also reduces resistance.

Meanwhile, there are steps everyone can take to help in the battle against antibiotic tolerance and resistance. You can do this by taking the antibiotic exactly as prescribed by your doctor and finishing the entire bottle.

Brief, inconsistent exposure to the drug primes the bacteria to become tolerant and eventually resistant. Smarter use of antibiotics by all can stop the development of tolerant bacteria.Conversation

Megan Keeler, Ph.D. Candidate in Microbiology, Cornell University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

By admin

Leave a Reply

Your email address will not be published. Required fields are marked *