A new study, published in the Journal of Medicinal Chemistry, offers the first proof that a new synthetic form of the antibiotic teixobactin can neutralize drug-resistant bacteria.
The Centers for Disease Control and Prevention (CDC)
In the United States alone,
The threat of antibiotic-resistant pathogens is particularly high in healthcare facilities.
In fact, a 2016 report by the CDC shows that
- Carbapenem-resistant Enterobacteriaceae
- Methicillin-resistant Staphylococcus aureus (MRSA)
- ESBL-producing Enterobacteriaceae
- Vancomycin-resistant Enterococcus (VRE)
- Multidrug-resistant Pseudomonas aeruginosa
- Multidrug-resistant Acinetobacter
Three years ago, scientists discovered that a natural antibiotic called teixobactin might have the potential to kill off MRSA and VRE.
Now, a team of researchers has created, for the first time, a synthetic version of the drug, which was used successfully to treat an infection in mice.
The new antibiotic has been called “game-changing,” and the findings may “lead to the first new class of antibiotic drug in 30 years.”
Ishwar Singh, a drug design specialist and senior lecturer in biological chemistry at the University of Lincoln’s School of Pharmacy in the United Kingdom, is the corresponding author of the new study.
Singh and colleagues studied the structure of teixobactin and found key amino acids that, when replaced, made the antibiotic easier to replicate into 10 synthetic analogs.
The team then tested these synthetic versions in vitro. “These [analogs],” write the authors, “showed highly potent antibacterial activities against Staphylococcus aureus, MRSA, and [VRE].”
Also, one of these analogs was found to be noncytotoxic both in vitro and in vivo, report the scientists.
Further tests in mouse models — carried out by a team at the Singapore Eye Research Institute in Bukit Merah — revealed that one of the analogs successfully treated a case of Staphylococcus aureus keratitis.
Specifically, using the synthetic drug “decreased the bacterial bioburden [by more than 99 percent] and corneal edema significantly as compared to untreated mouse corneas.”
The researchers write, “Collectively, our results have established the high therapeutic potential of a teixobactin [analog] in attenuating bacterial infections and associated severities in vivo.”
Singh explains the significance of the findings, saying, “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.”
“A significant amount of work remains,” continues Singh, “in the development of teixobactin as a therapeutic antibiotic for human use,” adding that “we are probably around six to ten years off a drug that doctors can prescribe to patients.”
Still, “this is a real step in the right direction and now opens the door for improving our in vivo [analogs],” he says.
“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.”
Ishwar Singh
“Drugs that target the fundamental mechanism of bacterial survival, and also reduce the host’s inflammatory responses are the need of the hour,” concludes study co-author Rajamani Lakshminarayanan, of the Singapore Eye Research Institute.