We know that most of our antibiotics have come from nature- in particular, we find candidate microbes from soils around the world that produce these compounds. However, the compounds we have developed as our antibiotics were all “recoverable” from their environment.
Which means a great deal of new antibiotics findings may still be possible, if we can find ways to culture, to grow the microbes responsible for these compounds. These have now have been termed the ”unculturable microbes”. Creative scientists have developed procedures to recover and exploit these compounds.
(Note; This is similar to what was found with bicarbonate dialysates. A microbe that did not grow on conventional media- and took 7 days of incubation- could infect this critical medical component. Once the protocols were developed, it became possible to ensure it would never infect a patient.)
Two such creative scientists are Drs. Kim Lewis and Slava Epstein. These professors at Northeastern University (Boston, MA) have developed a library of techniques to discover and exploit these compounds. They founded NovoBiotic Pharmaceuticals in Cambridge, MA, so they could market the antibiotics they develop.
One such novel entity, Clovibactin, was found and isolated from the sandy soils of North Carolina. It’s internal code name is Novo29. It has been found to be effective against MRSA in laboratory testing. But, most interestingly, its mode of action is completely different from that of conventional antibiotics.
Conventional antibiotics target the cell wall (actually the enzymes that assemble the cell wall) that normally protects the microbe from the environment. This cell wall is a rigid, mesh-like structure that surrounds the cell membrane. Conventional antibiotics disrupt the cell wall, which means the cells then burst and die. (Note that animal cells do not have cell walls, so they are generally not affected by the antibiotics.)
What makes clovibactin different from these other antibiotics is its target and mode of action. It also targets gram positive microbes. Gram positive microbes have a thick layer of peptidoglycan. Gram negative microbes have a thin layer of peptidoglycan and an additional outer membrane. (They are identified by the way they stain when treated with a dye called the Gram stain. Gram positives are blue or purple under the dye while Gram negatives and pink or red.)
Clovibactin targets pyrophosphate that is a vital component of three different building blocks of the cell walls. (This does mean for the microbe to evade the clovibactin attack, it would have to modify all three building blocks; a far more difficult task than that taken when antibiotic resistance is developed by a cell, which only requires one protective mode to mutate.) Moreover, clovibactin employs a hydrophobic interface that it tightly wraps around pyrophosphate (the structural elements of its precursors).
It seems that clovibactin is about twice as effective (as determined by cell lysis) as vancomycin (our current prime drug of choice) against MRSA (methicillin resistant Staphylococcus aureus).
So, it wasn’t surprising that the researchers have yet to find any developed resistance to clovibactin. The drug is undergoing testing to determine the parameters of action and the dosage required to ensure successful termination of MRSA. As of now, there have been no adverse affects when tested in mice, but additional years of testing are contemplated.
Juneteenth (now a Federal holiday called the Juneteenth National Independence Day dates back to 19 June 1865, when Major General Gordon Granger posted the Emancipation Proclamation (2.5 y after first proclaimed by President Abraham Lincoln) and General Order 3 on the door of the Reedy Chapel AME Church in Galveston, TX. The general had taken control of Texas after the surrender and end of the Civil War and was to enforce Reconstruction in the area. It has been broadly celebrating African-American culture. Juneteenth was designated a federal holiday in 2021, when President Joe Biden signed the Juneteenth National Independence Day Act into law.
