|The iChip culture method. |
Al Granberg. https://www.the-scientist.com/
In 2017, another new class of antibiotics was discovered at Rockefeller University using just bioinformatic analysis of DNA extracted from the environment; this group didn’t even have to grow the bacteria in the lab. They based their strategy on the knowledge that there is a family of calcium-dependent antibiotics. By isolating DNA directly from environmental samples and searching for sequences that featured the known calcium-binding signature, they could identify genes that potentially encoded new calcium-dependent antibiotics. They then transferred these DNA sequences into bacteria that can be cultured for further study. The new antibiotic class they found, the malacidins, also interferes with the ability of bacteria to properly form cell walls. Malacidins were shown to clear MRSA infections in the cut wounds of rats. Importantly, even after 3 weeks of exposure to the drug, there was no sign of resistant bacteria. This finding suggests that the mechanism of action for the malacidins is one that cannot be circumvented easily by the bacteria, which bodes well for their use against multidrug-resistant pathogens.
A third novel class of antibiotics was just described earlier this month in the journal Molecular Cell by researchers from the University of Illinois at Chicago and the biotech company Nosopharm. This class, called the odilorhabdins, was isolated from a bacterium that lives in a symbiotic relationship with a nematode worm in soil. This bacterium secretes a number of compounds that help the nematode colonize and kill insects and keep the insect carcass from being invaded by other bacteria or fungi. The odilorhabdins exert their antimicrobial activity by interfering with bacterial protein production. While several other antibiotics also target this process, the odilorhabdins bind to a unique site on the bacterial ribosome (the part of the cell responsible for making proteins); this means that bacteria that are resistant to other antibiotics that interfere with protein production will not be resistant to the odilorhabdins. When tested for their ability to kill several pathogenic bacteria in culture, the odilorhabdins were highly effective. One of the odilorhabdins, NOSO-95179, was also tested in mice and could significantly reduce Klebsiella pneumoniae septicemia and lung infection.
|MRSA (green) being enveloped|
by a white blood cell.
CDC's Public Health Image Library.
Image # 18126; photo credit: NIAID.