Widespread introduction of antibiotics began in the 1940s with penicillin and streptomycin, which transformed medicine and provided effective cures for the most common diseases of the time. However, resistance developed the limits of the lifespan of antibiotics and resulted in the requirement for constant introduction of new compounds. Researchers are desperately trying new tactics to find antibiotics that will not be resisted. For example tactics include using probiotics to stimulate our own defenses, to stop using broad-spectrum drugs and curb the virulence and save our healthy bacteria, chemically and synthetically modify existing antibiotics to prevent resistance, treatments like CIPRO that turn off the bodies’ SOS response and prevent resistance as well as many other tactics. Isolating bacteria from soil and fungi has been an idea for a while but scientist thought they had exhausted this idea until now. “Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was over mined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform.” In addition, “most antibiotics in clinical use were discovered by screening cultivable soil microorganisms, a much depleted resource that has not been adequately replaced by synthetic approaches. Hence the widespread alarm at the spread of antibiotic resistance.”
In the January issue of Nature Magazine, authors discussed how uncultured bacteria make up about 99% of all species in external environments and are and “untapped” source of new antibiotics. Developments of new methods to grow uncultured organisms that were previously uncultivable, by cultivation in situ or by using specific growth factors have lead to the new antibiotic, after identifying a β-proteobacterium, Eleftheria terraesp that produces a depsipeptide they call teixobactin. “Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid).” The drug is active in vivo and separately targets precursors in the biosynthetic pathways for each of two major components of the bacterial cells wall, peptidoglycan and teichoic acic. Most importantly, this drug is that it did not obtain any mutant of Staphylococcus aureus or Mycobacterium tuberculosis resistant to Teixobactin, perhaps a consequence of the novel two-target mechanism.
The name of the drug plays off the Greek word teixos, for wall, since it inhibited the building of the cell wall and explains how the drug works in the most simple of terms.
Lewis, who is a founder of NovoBiotic Pharmaceuticals, said that there is still work to be done to make teixobactin more soluble and test its safety, so clinical tests are several years away. However, more positively to conclude, “There’s maybe, potentially, two orders of magnitude or 100 times as many classes of antibiotics that we haven’t discovered yet,” said Dr. Michael Kurilla, director of the office of biodefense, research resources, and translational research at the National Institute of Allergy and Infectious Diseases, who was not involved in the study. “This is where everything has to start, and this is as promising and exciting as we’ve seen in awhile.” Though this is not the only drug that is not facing resistance, it is a new finding with lots of promise for itself and for many other soil samples to cultivate into drugs in the future.
Lewis, K.-University Distinguished Professor; Director, Antimicrobial Discovery Center.
Ling, L et. Al. A new antibiotic kills pathogens without detectable resistance in Nature Magazine. 22 January 2015. Macmillan Publishers Limited.
New Martin, G. A new antibiotic kills pathogens without detectable resistance. Originally published in news@northeastern. 7 January 2015.http://www.northeastern.edu/cos/2015/01/kim-lewis/