New class of antibiotic synthesized from the microbiome.
Antibiotics are medicines used to prevent and treat bacterial infections. Antibiotic resistance occurs when bacteria adapt in response to the use of these medicines and become immune to their mode of action. The infections these bacteria cause in humans or animals are harder to treat than those caused by bacteria which are not antibiotic resistant. There is an urgent need for behavioural changes such as actions to reduce the spread of infections through vaccination, hand washing, practising safer sex, and good food hygiene, as well as newer classes of antibiotics. Now, a study from researchers at the University of Tübingen synthesizes a new class of antibiotic from the microbiome. The team state the newly discovered fibupeptides impair the energy supply to the bacterial cell consequently causing their death. The study is published in the journal Angewandte Chemie.
Previous studies show infections caused by antibiotic-resistant bacteria, such as Staphylococcus aureus (MRSA) whose natural habitat is the human nasal cavity, are among the leading causes of death worldwide. Recent studies from the lab discovered that Staphylococcus lugdunensis which colonizes in the human nose produces a previously unknown antibiotic. The researchers observed that MRSA is rarely found when Staphylococcus lugdunensisis is present in the nose. Tests in mice showed, the substance dubbed lugdunin was able to combat multiresistant pathogens, where many classic antibiotics have become ineffective. The current study synthesizes lugdunin and determines the chemical properties responsible for its effects, and the antibiotic’s mode of action.
The current study synthesizes numerous lugdunin derivatives, altering parts of the chemical structure to identify the structures responsible for lugdunin’s antibiotic effect. Results show lugdunin consists of a ring of amino acid building blocks, a peptide structure, with a built-in characteristic sulphur-nitrogen bond, termed thiazolidine. The new class of agents have been named fibupeptides. Data findings show the thiazolidine ring is one of the structures which are essential for the antibacterial effect.
The group explain that fibupeptides such as lugdunin are able to transport positively charged hydrogen ions across the membrane and consequently dissipate this membrane potential, resulting in an energy standstill, which kills the bacterial cell. They go on to add that as the antibiotic effect remained unchanged in a chemically synthesized mirror image structure of lugdunin, the antibiotic effect based on spatial interactions could be ruled out. They conclude that this lack of spatial interactions is advantageous for avoiding resistance.
The team surmise they have synthesized an antibiotic produced by the microbiome which kills bacteria by disturbing energy metabolism. For the future, the researchers state preclinical and clinical trials are required to evaluate whether fibupeptides can be used as therapeutic candidate agents in future.
Source: University of Tübingen