Biophysicists develop a computer model that shows the effect of antiseptics on bacterial membranes



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A team of biophysicists from leading Russian research and education institutions (MSU, RUDN University and the Federal Research and Clinical Center of the Federal Biological Medical Agency of Russia) has developed a computer model showing the effect of antiseptics on bacterial membranes .

Common concepts related to the mode of action of antiseptics have turned out to be wrong: instead of destroying bacterial membranes, they cause changes in their structure. These changes make the bacteria weaker and more susceptible to adverse external factors. The results of the study were published in The Journal of Physical Chemistry.

Antiseptics are chemical agents that affect the internal processes or external structures of harmful microorganisms by causing them to die. For example, alcohols break down important building and regulation blocks of bacteria and viruses.

Other antiseptics target the integrity of bacterial membranes. They are effectively used against a wide range of pathogens, but their mode of action remains elusive. Scientists are aware of some general patterns, such as the presence of electrically charged particles in the molecules of antiseptic agents.

The team developed a computer model of a bacterial membrane and discovered the mechanism of antiseptic activity. The results of the study can help fight bacterial resistance.

Some pathogens, particularly those associated with hospital infections, show resistance to antiseptics. It is important to understand the physics behind the interaction of antiseptics and microorganisms to use antiseptics more efficiently and to develop new agents. “

Ilya Kovalenko, PhD, Professor and Doctor of Science in Physics and Mathematics, Working Under Project 5-100, RUDN University

Scientists developed a bacterial membrane model and applied molecules of four antiseptics (miramistin, chlorhexidine, picloxydine and octenidine) to it. All these substances are cationic antiseptics, that is, their molecules are positively charged.

However, to the surprise of the researchers, the antiseptics failed to damage the membrane and only slightly changed its structure. Even when the ratio of membrane antiseptics to lipids was increased from 1/24 to 1/4, the membrane was not destroyed.

The destruction of the membrane occurred only when an external electric field (with intensity of 150 mV / nm) was added to the model. The membrane began to restructure and pores began to form around the antiseptic molecules.

Then the water entered them and enlarged them; and eventually, the membrane was torn apart. This is because the membrane thinned around positively charged molecules: the membrane molecules had no charge and were therefore pushed away. An irregular membrane became more susceptible to adverse external factors, which led to cell death.

“We investigated the reaction of the model membrane to different cationic antiseptics and found that structural changes in the membrane in the presence of an electric field play a key role in pore formation. We plan to use this model to predict the effect of existing and new antiseptics on various microorganisms, ”added Professor Ilya Kovalenko, Ph.D., Ph.D. in physics and mathematics, working under the 5-100 project at RUDN University.

Source:

Journal reference:

Kholina, EG, et al. (2020) Cationic antiseptics facilitate pore formation in model bacterial membranes. The Journal of Physical Chemistry B. doi.org/10.1021/acs.jpcb.0c07212.

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