Scientists Inspect Superbugs to Find out Their Reaction to Antibiotics

Researchers have found how single-celled organisms have outplayed us. Namely, it would seem that the tiny bacteria in our guts have adopted a clever method which helps them resist our antibiotics. According to a report, the two-part system is beneficial for them in that it keeps them alive. Additionally, they are able to withstand everything as another bacterium brings them a lifeline. This one is located in one part of DNA. So we can say that microbes have won this round!

The study leader Christian Lesterlin said that these findings worked in favor of bacterial cells. Admittedly, he and his colleagues were already aware that these superbugs could fight off our medicine. But they did not understand how they succeeded in doing that. The scientists were impressed by their abilities. Mainly because these microbes could survive and adapt in a severe environment with antibiotics. Yet the researchers feel hopeful, as they believe that these results can help them do more for human health.

The History of Our Battle with Bacteria

For a bigger part of our history, bacteria have prevailed over us. Of course, some are helpful, while others lead to diseases such as cholera, pneumonia, and meningitis. For instance, Yersinia pestis decreased the world’s population by 20% during the mid-1300s. This was when the pandemic Black Death spread across the globe.

And for a while, humans were successful in their fight against bacteria when scientists released antibiotics. A number of medicines focus on the machinery that carries the vital cell wall of a bacterium. Others strip bacteria from the important proteins which they use to perform necessary functions. Alternatively, they can utilize them to harm the DNA. 

What’s more, the first drug-resistant strains became visible only after a few decades. And every creation of a new antibiotic led to a fierce reply from the bacteria. So physicians would deal with this by prescribing a different antibiotic. Then they would combine two or three medicines. We still have some resources to combat them. But it would seem that certain diseases, such as Acinetobacter, Klebsiella pneumoniae, Escherichia coli, and Enterococcus, are not easy to overcome. And we are yet to discover medicine that could fight them off.

Understanding the Tactics

Scientists are pulling out all the stops in order to understand bacteria’s tactics. There are many burning questions. At this time, they want to discover how antibiotic resistance develops within bacterial cells. Especially when antibiotics which aim to eliminate them altogether kick in. Also, bacteria are clever enough to know that they should not wait for a random mutation in their DNA to save them from an antibiotic. Namely, these mutations are rare. To be specific, around 1 in 10,000 bacteria are able to develop resistance to some medicines.

And for other drugs, one in a billion are able to do this. So as you can tell, this is not exactly efficient. But they can always rely on plasmids. In essence, they are circular snippets of DNA. And they can come in handy because they have genes that include instructions on how to combat a certain antibiotic. Additionally, bacteria can exchange helpful plasmids with each other.

Furthermore, the team of researchers wanted to see how this exchange occurred. Thus, they placed a strain of Escherichia coli bacteria in a petri dish. In another dish, they put a strain that was impervious to the antibiotic tetracycline. After this, they poured tetracycline in both plates and examined them closely. Of course, they expected that those cells which were not resistant to the medicine would perish. But this did not happen — they only went to sleep. 

After a couple of hours, they decided to merge the contents of the two plates. And then they relied on live-cell microscopy that would help them watch what would transpire. So they saw that it took only two minutes for plasmids to transfer from tetracycline-resistant bacteria cells to tetracycline-sensitive ones. And they did not stop there. Namely, about two hours later, they created a protein TetA resistance factor. With it, they were finally resistant to tetracycline.

Further Implications

According to Lesterlin, they did not anticipate this to happen. So now they had to find out how bacteria were able to produce drug-resistance proteins while a protein-inhibiting medicine was present. It seems that there is no such thing as too many accessories for bacteria! For instance, the AcrAB-TolC multidrug efflux pump rests on the outer membrane of the cell. While there, it expels many toxic antibiotics that permeate the interior of the cell.

Even though it sounds fancy, this pump is not sufficient, as the cell will not continue to thrive in the presence of antibiotics. Nevertheless, the cell has enough time to develop a plasmid which will have a resistance gene. During this research, the pump maintained low levels of tetracycline. So the cell was able to transform the aforementioned gene into a TetA protein that was unsusceptible to the antibiotic. This protein kept the drug-resistant cell alive; thus, it multiplied and grew. 

Moreover, Lesterlin stated that, because of the multidrug efflux pump, bacteria remained asleep. They were neither dead nor alive — they were waiting for some assistance from its neighbor. These rudimentary microbiology findings might seem not to focus on the actual war on the superbugs. However, it is paramount to study your enemy first. And getting to the bottom of how basic cells operate might tell us what we are missing when fighting against antibiotic resistance.

Other Reactions

Vanessa Povolo of the Swiss Federal Institute of Technology said that the scientists came across a key piece of the puzzle. In other words, their results suggest that there is collateral damage because of our approach to combating bacterial infections. As per their belief, it is not a good thing to overuse drugs, as it has encouraged bacteria to create resistant strains in our digestive tracts. As they now understand how plasmid transfers work, they can try to come up with new treatments that will assault the multidrug efflux pumps.

In addition, Shaun Yang, assistant medical director of the Clinical Microbiology Laboratory at UCLA, states that bacteria resort to many weapons. So it is not plausible for us to remove one weapon and believe that we’ll succeed in our battle. 

For the time being, scientists are in a race that could determine the fate of all organisms. One reports states that antibiotic-resistant bacteria are the cause of death for about 23,000 people in the United States each year. Furthermore, the United Nations remind that drug-resistant infections could end up killing 10 million people per year by 2050 if we do not take any actions. This hardly comes as a surprise mainly because bacteria possess a few billion years of experience in this long war.