"Game-changing" synthesized antibiotic successfully treats infections for the first time

Authored by newatlas.com and submitted by mvea

A synthesized version of a new antibiotic is proving successful in early animal trials, bringing researchers one step closer to producing a useful new antibiotic to help in the war against superbugs(Credit: katerynakon/Depositphotos )

Back in 2015, a team of scientists discovered an exciting new antibiotic called teixobactin. Now an international team of researchers has, for the first time, successfully synthesized the compound and used it to treat a bacterial infection in mice. This is an important milestone in the quest to develop a new antibiotic in the war against antibiotic-resistant superbugs.

"When teixobactin was discovered it was groundbreaking in itself as a new antibiotic which kills bacteria without detectable resistance including superbugs such as MRSA, but natural teixobactin was not created for human use," explains Ishwar Singh, one of the scientists involved in the new research.

Late last year, a University of Lincoln team revealed it had successfully developed a synthesized version of teixobactin, with an easier synthesis process speeding up a single coupling step from 30 hours to just 10 minutes. At the time, the potency of the new synthesized drug was only demonstrated in vitro.

Now researchers from the Singapore Eye Research Institute have shown the synthetic version of the drug can successfully kill Staphylococcus aureus keratitis in live mouse models. The drug also reduced the severity of the infection in the animals, which was unexpected as the conventional clinically used alternative, moxifloxacin, does not display that extra effect.

"Translating our success with these simplified synthetic versions from test tubes to real cases is a quantum jump in the development of new antibiotics, and brings us closer to realizing the therapeutic potential of simplified teixobactins," says Singh.

Teixobactins represent an exciting new class of antibiotics, the first novel antibiotic isolated from bacteria in over 30 years. Since its 2015 discovery another new family of antibiotics called malacidins were revealed in early 2018. This discovery is still in its early stages, and not nearly as developed as the latest research on teixobactin, which is still are a few years away from reaching our medical clinics.

"A significant amount of work remains in the development of teixobactin as a therapeutic antibiotic for human use – we are probably around six to 10 years off a drug that doctors can prescribe to patients – but this is a real step in the right direction and now opens the door for improving our in vivo analogs," says Singh.

KrapXela on March 26th, 2018 at 14:19 UTC »

What's even more interesting is the method they used to isolate the microorganism that produced teixobactin. If I remember correctly, they use something they called the iChip, which allowed them to grow the organisms in their natural environments and slowly transition them to standard petri dishes. The main idea behind this is that out of all the microorganisms available less than 1% is actually cultivatable in lab setting which is why the production of new antibiotics has been stinted.

Found it:

The nature paper in 2015 that characterizes Teixobactin

The paper published in 2010 detailing how the iChip works

cr0ft on March 26th, 2018 at 12:29 UTC »

Hopeful news. The antibiotic crisis is a pretty major sword of Damocles hanging over us.

Of course part of the fix is to get people to be responsible about using antibiotics in the first place.

mvea on March 26th, 2018 at 10:37 UTC »

The post title is a copy and paste from the following sections of the linked popular press article here :

First paragraph:

Back in 2015, a team of scientists discovered an exciting new antibiotic called teixobactin. Now an international team of researchers has, for the first time, successfully synthesized the compound and used it to treat a bacterial infection in mice.

And sixth paragraph:

Teixobactins represent an exciting new class of antibiotics, the first novel antibiotic isolated from bacteria in over 30 years.

Journal Reference:

Design and Syntheses of Highly Potent Teixobactin Analogues against Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA), and Vancomycin-Resistant Enterococci (VRE) in Vitro and in Vivo

Anish Parmar†¶, Rajamani Lakshminarayanan‡¶, Abhishek Iyer†§, Venkatesh Mayandi‡, Eunice Tze Leng Goh‡, Daniel G. Lloyd∥, Madhavi Latha S. Chalasani⊥, Navin K. Verma⊥‡, Stephen H. Prior#, Roger W. Beuerman‡, Annemieke Madder§, Edward J. Taylor∥ and Ishwar Singh†

Journal of Medicinal Chemistry, Vol. 61: , Issue. 5, : Pages. 2009-2017

DOI: https://doi.org/10.1021/acs.jmedchem.7b01634

Link: https://pubs.acs.org/doi/10.1021/acs.jmedchem.7b01634#/doi/full/10.1021/acs.jmedchem.7b01634

Abstract:

The cyclic depsipeptide, teixobactin, kills a number of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium tuberculosis without detectable resistance. To date, teixobactin is the only molecule in its class that has shown in vivo antibacterial efficacy. In this work, we designed and synthesized 10 new in vivo ready teixobactin analogues. These analogues showed highly potent antibacterial activities against Staphylococcus aureus, MRSA, and vancomycin-resistant enterococci (VRE) in vitro. One analogue, d-Arg4-Leu10-teixobactin, 2, was found to be noncytotoxic in vitro and in vivo. Moreover, topical instillation of peptide 2 in a mouse model of S. aureus keratitis decreased the bacterial bioburden (>99.0% reduction) and corneal edema significantly as compared to untreated mouse corneas. Collectively, our results have established the high therapeutic potential of a teixobactin analogue in attenuating bacterial infections and associated severities in vivo.