Malacidine
Vorlage:Chembox Malacidins are a class of chemicals made by bacteria found in soil microbiomes but not reported in microbiological culture-based studies. The discovery of malacidins was published in 2018.[1] At the time of the publication it was not certain if the discovery would lead to any new antibiotic drugs; it takes many years and millions of dollars to determine if a drug is safe and effective.[2]
Chemical structure
The malacidins are cyclic lipopeptides differing only by a methylene at their lipid tails.[1] Their peptide cores include four non-proteinogenic amino acids.[1] The name "malacidin" is a shortening of the full name "metagenomic acidic lipopeptide antibiotic-cidins."[3]
Discovery
Malacidins were discovered by researchers at Rockefeller University, led by Brad Hover and Sean Brady. The group had been looking into antibiotics related to daptomycin and their calcium-dependent nature, but determined that it would be impractical to culture variations in lab conditions.[3] Instead, the team used metagenomics and gene sequencing to study micro-organisms from nearly two thousand soil samples taken across the United States, as to evaluate the types of secondary metabolites these micro-organisms generate to sustain themselves within the harsh soil conditions. Their analysis showed the malacidins appearing in more than 19% of the samples. They were able to determine the relevant DNA from organisms that produced these antibiotics, insert these into a host, and generate sufficient quantities of malacidins for further testing.[3] The work was published in Nature Microbiology in February 2018.[1][4]
Only one other class of antibiotics (teixobactin) had been discovered in the preceding 33 years.[5]
Mechanism of action
Malacidins act by a calcium-dependent interaction with lipid II, a bacterial cell wall precursor molecule; such interactions should not affect the cells of a host body and make the antibiotics non-toxic to the host.[1][2] At the time of the publication, Brady's team believed that the calcium dependence for malacidins helps prevent microbes from evolving resistance to the antibiotic.[2]
They are therefore a member of the class of calcium-dependent antibiotics.[1][2] The discovery of the malacidins supported the view that the calcium-dependent antibiotics are a larger than previously thought class.[1]
Research directions
The approach of "mining" the soil for antibiotics has the potential to discover further classes of antibiotics that otherwise cannot be developed under laboratory conditions.[2]
At the time of the discovery it was unknown whether the discovery would lead to any actual new antibiotic drugs; showing that a potential drug is safe and effective takes years of work and millions of dollars.[2] In the 2018 paper, malacidins were shown to treat only Gram-positive infections,[1] but were able to kill multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) skin infections in an animal wound model.[1]
References
- ↑ a b c d e f g h i Bradley M. Hover, Seong-Hwan Kim, Micah Katz, Zachary Charlop-Powers, Jeremy G. Owen, Melinda A. Ternei, Jeffrey Maniko, Andreia B. Estrela, Henrik Molina, Steven Park, David S. Perlin, Sean F. Brady: Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens. In: Nature Microbiology. 12. Februar 2018, doi:10.1038/s41564-018-0110-1.
- ↑ a b c d e f Sarah Kaplan: A potentially powerful new antibiotic is discovered in dirt. In: The Washington Post. 13. Februar 2018, abgerufen am 13. Februar 2018.
- ↑ a b c Melissa Healy: In soil-dwelling bacteria, scientists find a new weapon to fight drug-resistant superbugs. In: Los Angeles Times. 13. Februar 2018, abgerufen am 13. Februar 2018.
- ↑ New antibiotic family discovered in dirt. In: BBC. 13. Februar 2018, abgerufen am 13. Februar 2018.
- ↑ Alex Matthews-King: A whole new class of antibiotics has been discovered in soil In: The Independent, 13 February 2018. Abgerufen im 14 February 2018