Once the research community succeeds in developing a new antibiotic to deal with bacteria, after a period of time the bacteria develop resistance to this drug, in what resembles a game of “cat and mouse” between the two parties.
But an international research team led by researchers from Texas A&M University is one step away from settling this game in favor of the patient, thanks to a new family of polymers that target the membrane of these microorganisms, killing bacteria without causing drug resistance.
Antibiotic-resistant bacteria have become an increasing threat to public health, as they directly cause 1.27 million deaths each year, in addition to indirectly causing 4.95 million deaths, according to study The famous journal The Lancet was published on November 21, 2023.
Bacteria develop resistance to antibiotics in several ways:
- Edit target: They modify their genetic material, changing the target site, where the antibiotic usually binds to and disrupts cellular processes. This change prevents the antibiotic from interacting effectively with its intended target, rendering it ineffective.
- Flow pumps: Some bacteria develop specialized proteins called efflux pumps that effectively pump antibiotics out of the bacterial cell, reducing the concentration of the drug inside the cell and reducing its effect.
- Resistance gene transfer: Bacteria can transfer genetic material – including genes that confer resistance to antibiotics – to other bacteria through mechanisms such as conjugation, and this process allows resistance genes to spread quickly among bacterial populations.
- Enzymatic hydrolysis: Bacteria may produce enzymes that chemically modify or destroy antibiotics before they can do their job. For example, beta-lactamase enzymes break down penicillin-type antibiotics, rendering them ineffective.
- Biofilm formation: Bacteria can form protective biofilms that act as shields against antibiotics, making it difficult for drugs to penetrate and reach bacterial cells.
- Dormancy or slow growth: Bacteria can enter a state of dormancy or slow growth, where they become less susceptible to antibiotics, because the drugs are more effective against cells that are actively dividing.
Targeting the bacterial membrane…a foolproof mechanism
Targeting the bacterial membrane using specific polymers is effective against bacteria while reducing the possibility of antibiotic resistance for several reasons, including:
- Somatoform disorder: The polymers work by physically disrupting the bacterial cell membrane, rather than targeting specific internal processes or molecules within the bacteria as traditional antibiotics do.
- Non-specific interaction: The polymers interact with the lipid membranes that envelop bacterial cells, causing damage to the structural integrity. This disruption leads to leakage of cell contents and ultimately cell death.
- Complex nature: The bacterial membrane is a critical and complex structure for the survival of bacteria, and targeting this structure with polymers affects multiple aspects of the cell rather than one specific target, making it difficult for bacteria to develop resistance.
- Low mutation rate: The mechanism of membrane disruption does not inherently cause bacteria to mutate at a high rate compared to conventional antibiotics, and mutations in antibiotic target sites often lead to resistance. However, altering the membrane in a way that bypasses the action of these polymers is more complex and less likely to occur quickly.
Previous attempts…a common problem
Although polymers show effectiveness in resolving the “cat and mouse” game between drugs and bacteria, a common problem has prevented them from being used in drug production until now. The researchers claim the study What’s new, published in the Proceedings of the National Academy of Sciences journal, is that they have succeeded in overcoming it.
The common method for manufacturing polymers used in medicines is based on the “multiple condensation” method, which limits precise control over their design in a way that allows for selectivity. This selectivity makes them differentiate between bacteria and human cells when targeting the cell membrane, which is a problem that researchers succeeded in solving by designing polymers in a way New.
Polycondensation is a method of manufacturing polymers by joining monomers (a molecule that forms the basic unit of polymers) through a condensation reaction, which usually involves the removal of small molecules such as water, alcohol, or hydrogen chloride. This process occurs in steps, in which monomers with functional groups (for example, hydroxyl and carboxyl groups) react to form polymer chains.
The manufacturing process begins with monomer activation, where monomers with reactive functional groups undergo activation, often through heating or the presence of a catalyst. Then the activated monomers interact with each other and form covalent bonds between their functional groups. When bonds are formed, small molecules such as water or compounds are eliminated. others as byproducts, and the polymer chains continue to grow as more monomers react, until the desired chain length is achieved.
However, the most notable disadvantage of this method is the “lack of control.” Polycondensation often lacks precise control over chain length, which leads to a wide distribution of molecular weight and varying polymer properties, a problem that researchers addressed using the “controlled polymerization” technique.
Controlled polymerization refers to a set of techniques used in polymer chemistry to precisely control the growth of polymer chains, resulting in species with well-defined structures, controllable molecular weights, and specific functions.
Greater effectiveness…a new polymer
If we imagine the process of building polymer chains as being similar to “building a toy train with special cubes,” then using “controlled polymerization” the researchers created a new type of train tracks by designing a special block that can be easily linked together several times to create a long track, and each block has a special charge that attracts They attracted each other like a magnet, making the entire path of one type of charge, and a unique and new catalyst called “Aquamate” – which is like magic glue – was used to glue these blocks together.
Quentin Michaudel, assistant professor in the Department of Chemistry at Texas A&M University, said: statement A journalist published on the university’s website: “This glue is very important, because it tolerates a high concentration of charges, and it is also soluble in water, which is an uncommon feature in this type of operation.”
Michaudel and his research team tested the new polymer against two main types of antibiotic-resistant bacteria, namely, “Escherichia coli” and “Staphylococcus aureus,” and proved effective in targeting them. The researchers also tested the toxicity of the polymer against human red blood cells, and gave very encouraging results.
The research team aims to enhance the activity of these polymers against bacteria while improving their selectivity for bacterial cells. They are currently assembling different versions of the polymers to achieve these goals, and are planning to conduct in vivo experiments in the near future.
Long term tests
For his part, Mohamed Mansour, professor at the Faculty of Pharmacy at the Egyptian University of Beni Suef, praises the results achieved in this study on a laboratory scale, but stresses that the new polymer needs long-term tests to ensure that bacteria will not develop resistance against it.
Mansour said in a telephone interview with Al Jazeera Net: “Confirming this fact requires long-term tests to ensure that resistance does not develop over time. We must also verify the accuracy of the polymers in distinguishing between bacterial cells and human cells, and this will also need to be done.” “Long time to prove.”
He adds, “If these two matters are resolved, we will have an important breakthrough in resolving the ongoing battle between drugs and bacteria.”