Malacidine
Malacidins are a group of lipopeptides that experimentally show antibiotic activity. The name is derived from Malacidin m etagenomic a cidic l ipopeptide a ntibiotic (= "metagenomes acidic lipopeptide antibiotic") and the suffix "-cidin".
Occurrence
Malacidins are produced by bacteria found in soil .
Chemical structure
Malacidins are macrocyclic lipopeptides that differ in the chain length of the lipid side chain. The peptide unit consists of four non-proteinogenic amino acids . Malacidin A has a methyl group on the acyl group (a lipid), while malacidin B has an ethyl group.
effect
Malacidins are effective against Gram-positive , but not against Gram-negative bacteria. Their effect depends on the presence of calcium ions .
In laboratory tests, resistant pathogens could be combated with the substances, for example vancomycin- resistant bacteria and the methicillin- resistant bacterial strain Staphylococcus aureus ( MRSA ) in skin infections of wounds.
By binding to calcium, the malacidins take on their active form. The resulting complex binds to a lipid and becomes the bacterial precursor of a cell membrane, which leads to the destruction of the cell membrane and ultimately to the death of the bacterium. The malacidins therefore belong to the class of calcium-dependent antibiotics . The discovery of malacidins supports the thesis that the substance class of calcium-dependent antibiotics is larger than previously assumed.
It is currently still uncertain whether the properties of the malacidins can lead to new antibiotic drugs .
history
Various soil samples were screened for potentially useful active substances , a suitable method to study primary and secondary metabolites of microorganisms.
The discovery of malacidins was published in 2018 by Rockefeller University scientists from the group of Brad Hover and Sean Brady. The group had studied antibiotics containing the calcium-dependent drug daptomycin , but they found that variations in cell culture were unfavorable under laboratory conditions. Instead, the research team used a genetic approach that was more workable. They focused on finding new biosynthetic gene clusters (BGCs), and used bacteria to produce secondary metabolites . To do this, they extracted DNA from over 2,000 soil samples in order to create a gene library that reflects the genetic diversity of the microbiome 's environment . They produced a primer to amplify (replicate) the genes and synthetically created gene clusters similar to the antibiotic daptomycin using the polymerase chain reaction . They then metagenomically tested that these genes actually correspond to the expected BGCs. One of the new BGCs was present in 19% of the soil samples examined, but not often in microbiological collections. Meanwhile BGC were in a different bacterial strain transformed and cultured. The secondary metabolites were isolated from this and analyzed.
Individual evidence
- ↑ a b c Melissa Healy: In soil-dwelling bacteria, scientists find a new weapon to fight drug-resistant superbugs . In: Los Angeles Times . February 13, 2018. Retrieved February 13, 2018.
- ↑ a b c d e f g h i Bradley M. Hover et al .: Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens . In: Nature Microbiology . February 12, 2018. doi : 10.1038 / s41564-018-0110-1 . PMID 29434326 .
- ^ A b New antibiotic family discovered in dirt . In: BBC . February 13, 2018. Retrieved February 13, 2018.
- ^ Soil search unearths new class of antibiotics . In: Chemistry World , February 14, 2018.
- ↑ a b c Sarah Kaplan: A potentially powerful new antibiotic is discovered in dirt . In: The Washington Post . February 13, 2018. Retrieved February 13, 2018.
- ^ Scientists Unearth Hope for New Antibiotics . In: Wall Street Journal , February 12, 2018.