Stockholm [Sweden], 19 November (ANI): Researchers at Karolinska Institutet, Umeå University and the University of Bonn have identified a new group of molecules that have an antibacterial effect against many antibiotic-resistant bacteria.
The discovery could help develop new, effective antibiotics with few side effects.
The results of the study have been published in the scientific journal ‘PNAS’.
The increasing resistance to antibiotics in the world is alarming, while few new types of antibiotics have been developed in the last 50 years. There is therefore a great need to find new antibacterial substances.
The majority of antibiotics in clinical use work by inhibiting the bacteria’s ability to form a protective cell wall, which causes the bacteria to burst (cell lysis). In addition to the well-known penicillin, which inhibits wall-building enzymes, newer antibiotics such as daptomycin or the newly discovered teixobactin bind to a special molecule, lipid II.
Lipid II is needed by all bacteria to build the cell wall. Antibiotics that bind to this cell wall building block are usually very large and complex molecules and therefore more difficult to improve with chemical methods. In addition, these molecules are mostly inactive against a group of problematic bacteria, which are surrounded by an additional layer, the outer membrane, which prevents the penetration of these antibacterial agents.
“Lipid II is a very attractive target for new antibiotics. We have identified the first small antibacterial compounds that work by binding to this lipid molecule, and in our study we found no resistant bacterial mutants, which is very promising,” says Birgitta Henriques Normark, professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and one of the article’s three corresponding authors.
In this study, researchers at Karolinska Institutet and Umeå University in Sweden tested a large number of chemical compounds for their ability to lyse pneumococci, bacteria that are the most common cause of community-acquired pneumonia.
The first tests were conducted in collaboration with the Chemical Biology Consortium Sweden (CBCS), a national research infrastructure at SciLifeLab. After a careful follow-up of active substances from this screening, the researchers, in collaboration with the University of Bonn in Germany, found that a group of molecules called THCz inhibits the formation of the bacterial cell wall by binding to lipid II.
The molecules could also prevent the formation of the sugar capsule that pneumococci need to escape the immune system and cause disease.
“The advantage of small molecules like these is that they are easier to change chemically. We hope to change THCz so that the antibacterial effect increases and any negative effects on human cells decrease,” says Fredrik Almqvist, professor at the Department of Chemistry at Umeå University and one of the corresponding authors.
In laboratory experiments, THCz has an antibacterial effect against many antibiotic-resistant bacteria, such as methicillin-resistant staphylococci (MRSA), vancomycin-resistant enterococci (VRE) and penicillin-resistant pneumococci (PNSP).
An antibacterial effect was also found against gonococci that cause gonorrhea and mycobacteria, bacteria that can cause serious diseases such as tuberculosis in humans. The researchers were unable to identify any bacteria that developed resistance to THCz in a laboratory setting.
“We will now also initiate attempts to alter the THCz molecule so that it can penetrate the outer cell membrane found in certain, especially difficult-to-treat, multi-resistant bacteria,” said Tanja Schneider, professor at the Institute of Pharmaceutical Microbiology at the University of Bonn and a by the corresponding author. (ANI)