May 20, 2022

This is how the Pseudomonas aeruginosa superbug responds to antibiotics – sciencedaily

The bacteria Pseudomonas aeruginosa is resistant to all the antibiotics on the market. Therefore, there is a great need for new therapeutic approaches. To find them, it helps to understand how the germ reacts to the active substances.

Researchers at the Ruhr-Universität Bochum (RUB) investigated how different drugs affect the hard-to-treat bacteria Pseudomonas aeruginosa. New treatment options for the pathogen are urgently needed, according to the World Health Organization, as some strains are already resistant to all currently approved antibiotics. The Bochum-based team led by Professor Julia Bandow revealed P. aeruginosa to various substances and observed their effects on the protein constitution of the bacteria, also known as the proteome. The results allow researchers to conclude what makes P. aeruginosa resistant; in addition, new approaches for the treatment of the priority pathogen have been investigated. Together with Prof. Pei Zhou’s group at Duke University in the United States, the RUB team describes the analyzes in “Antimicrobial Agents and Chemotherapy,” a journal of the American Society for Microbiology, published online November 8, 2021.

Bacteria are often classified as Gram-positive or Gram-negative depending on how they react in a certain staining procedure, namely the Gram stain. “Gram-negative pathogen infections Pseudomonas aeruginosa are feared as being difficult to treat, ”explains Julia Bandow, head of the applied microbiology research group at RUB. Patients can be infected with the germ in hospitals, for example; it causes pneumonia or sepsis, which can be fatal.

Specific properties could become targets for drugs

Gram-negative bacteria have a number of different properties than Gram-positive bacteria. For example, they produce sugar-lipid compounds characteristic of their outer membranes. “Some of the specific properties of Gram-negative bacteria could provide attractive targets for antibiotics,” explains Bandow. “This is what we are looking to exploit.

First, the researchers investigated why P. aeruginosa is resistant to so many common antibiotics. They treated the germ with twelve different approved antibiotics and documented the resulting changes in the proteome. This allowed them to deduce how cells defend themselves against antibiotics. The team also divided the individual substances into groups based on the similarity of the effects triggered. This correlated with similarities in the modes of action of the compounds.

In addition, scientists tested the test substance CHIR-090. Compared to the effects of approved antibiotics, CHIR-090 produced a unique proteomic response. CHIR-090 blocks the production of sugar-lipid compounds addressing a target that has not yet been exploited clinically. No drug resistance was observed in clinically relevant bacterial strains. “Resistance to new classes of substances should emerge more slowly than by derivatives of conventional antibiotics”, explains Julia Bandow.

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