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Discovering the Unseen Menace of Antibiotic Resistance!

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Have you ever had a severe infection that didn’t seem to go away? Or a recurring runny nose? Perhaps you are dealing with bacteria that are resistant to antibiotics, although not yet resistant to them.

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

Tolerance to antibiotics occurs when bacteria can survive for a long time after being exposed to an antibiotic. While antibiotic-resistant bacteria thrive even in the presence of an antibiotic, tolerant bacteria often dormant, do not grow or die, but co-exist with the antibiotic so they can “wake up” after the stress has passed.

Megan Keller, a microbiologist at Cornell University, studies antibiotic tolerance in an effort to find out what causes resistant bacteria to go into protective sleep. By understanding why bacteria are so hardy, researchers hope to develop ways to prevent this ability from spreading.

The exact mechanism that differentiates endurance from resistance has been 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 bacteria’s outer defenses.

Bacteria that can survive can remove their entire wall and avoid damage entirely. And if the threat disappears soon, the bacteria can rebuild their wall to protect it from other environmental threats and resume normal functions.

However, it remains unknown how the bacteria know that the antibiotic threat is over, and what exactly triggers their resurgence.

Researchers at Dörr’s lab at Cornell University are trying to understand the activation and awakening of the bacterium Vibrio cholerae, which causes cholera. Vibrio resistance is rapidly developing to various types of antibiotics, which causes concern among doctors.

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

To study how Vibrio develops resistance, a strain was chosen that is resistant to a class of antibiotics called beta-lactams, a cannonball sent to destroy the strength of the bacteria. Vibrio adapts by activating two genes that temporarily remove its cell wall.

After removing the cell wall, the bacteria activate more genes that turn them into fragile balls that can survive the impact of the antibiotic. Once the antibiotic is removed or dissolved, the vibrio returns to its normal penis shape and continues to grow.

In humans, this process of tolerance occurs when a doctor prescribes an antibiotic, usually doxycycline, to a cholera patient. The antibiotic temporarily stops the infection. But then the symptoms start to reappear because the antibiotics don’t completely remove the bacteria.

The ability to return to normal and grow after the antibiotic wears off is the key to survival. Long enough exposure of the vibrio to the antibiotic will eventually kill it. But standard antibiotic treatment is often not enough to get rid of all bacteria, even in their fragile state.

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

Other bacteria develop tolerance

Vibrios aren’t the only species showing hardiness. In fact, researchers have recently identified several infectious bacteria that have developed tolerance. And the family of bacteria called Enterobacteriaceae, which includes the major foodborne pathogens of Salmonella, are just a few of the many bacterial species that can tolerate antibiotics.

And since each bacterium is unique, the way resistance develops is unique. Some bacteria, such as Vibrio, wear out their cell walls. Others may change their energy sources, increase mobility, or simply administer an antibiotic.

It has recently been discovered that the metabolism of bacteria, or how they break down “food” for 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.

Blocking the bacteria’s ability to create these parts weakens their wall, making them more likely to be exposed to environmental damage before they can break down the wall.

While there is a wealth of research into how bacteria develop resistance, a major piece of the neglected puzzle is how this leads to resistance.

And in 2016, researchers figured out how to make bacteria resistant in the lab. After repeated exposure to various antibiotics, E. coli cells were able to adapt and survive. And DNA, the genetic material that contains the instructions for how cells function, is a fragile molecule.

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

Because E. coli is similar to many other types of bacteria, these researchers’ results showed that, ironically, virtually any bacteria can develop tolerance when pushed to the limit with antibiotics designed to kill them.

The last important discovery was that the longer bacteria were tolerant, the more likely they were to develop mutations leading to resistance. Tolerance allows bacteria to develop a resistance mutation that reduces their chances of dying during antibiotic treatment. This is especially important for bacterial communities that often appear in biofilms that tend to cover frequently touched surfaces in hospitals.

The researchers are calling for more antibiotic tolerance research in the hope that it will lead to more effective treatments for both infectious diseases and cancer.

Source: Science Alert

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