Antimicrobial resistance occurs when pathogens such as bacteria develop the ability to resist drugs designed to kill them. British researchers are now uncovering the underlying mechanisms of antibiotic resistance and hope that their knowledge will be used to develop new drug therapies.
Misuse and overuse of antibiotics contribute to the development of drug-resistant bacteria. Antibiotic resistance is a serious public health problem, increasing the likelihood that bacteria will spread more easily from person to person.
Gut bacteria have thin filamentous appendages called F-pilus that allow them to connect to each other and transfer antimicrobial resistance (AMR) gene packets. This is a process called conjugation. Initially, it was thought that the harsh conditions of the intestine (acidity, heat, and turbulence) adversely affected the F fimbriae, making gene transfer more difficult. found the opposite to be true: the ability of F pilus and AMR gene transfer is not affected by intestinal conditions and is enhanced by its molecular structure.
“Antimicrobial resistance is expected to kill as many people as cancer by 2050, which means that new strategies are urgently needed to combat this trend.” said Jonasz Patkowski, lead author of the study. “Much of the spread of resistant bacteria is driven by genetic exchange in bacteria, so a detailed understanding of this process could lead to new ways to stop it.
The researchers tested the existing hypothesis that F pili are fragile when excited by performing a simple experiment. Escherichia coli (Escherichia coli), a bacterium commonly found in the large intestine, where the F fimbriae are conjugated. They found that agitation actually increased the efficiency of gene transfer between bacteria. Importantly, they found that shaken bacteria agglomerate to form a biofilm, a kind of “fence” that protects the bacteria inside from surrounding antibiotic molecules.
Researchers keen to test the elasticity of the F fimbriae used “molecular tweezers” to pull on the ends of the structure and found that it was so elastic that it bounced back without breaking. The F fimbriae also withstood application of sodium hydroxide (caustic soda), urea, and temperatures of 212°F (100°C).
It is already known that F fimbriae are made up of subunits of linked phospholipid molecules, but researchers wanted to better understand their molecular composition. After creating the hair, the researchers repeated the pull test. Phospholipid-free F fimbriae readily collapsed, demonstrating how important these subunits are for structural strength and elasticity.
This study highlights how F fimbriae have adapted to spread AMR genes more efficiently and effectively, enhancing our understanding of antibiotic resistance and how the process is disrupted It is very helpful for
“Making F-piles is very costly for bacteria in terms of resources and energy, so it is not surprising that they are worth the effort.” have shown that they accelerate the rate of antibiotic resistance and biofilm formation, but the challenge now is to find ways to counteract this highly efficient process.”
Now that researchers have a better understanding of the strengths and weaknesses of the F fimbriae, they believe that their structure can be used to develop new drug delivery systems.
“It’s hard to find tubular appendages with properties that strong,” says Patkowski. “Bacteria use it to transfer genes, and if we could mimic these properties, we could use similar structures to deliver drugs exactly where they are needed in the body.”
The study was published in a journal Nature Communications.
Source: Imperial College London
