New antibiotics to kill drug-resistant bacteria are coming soon

Scientists may be approaching a new era of antibiotics.

According to the CDC, antibiotic resistance is "one of the world's most pressing public health problems."

In the US alone, 2 million people are infected with drug-resistant bacteria each year, resulting in more than 23,000 deaths.

The threat of antibiotic-resistant pathogens is particularly high in healthcare facilities.

A 2016 CDC report found that one-quarter of healthcare-associated infections occurring in long-term care settings were caused by one of the following six types of drug-resistant bacteria:

• 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 may have the ability to kill MRSA and VRE.

Now, a team of researchers has created a synthetic version of the drug for the first time and successfully used it to treat infections in mice.

The new antibiotic is seen as a landmark and the findings could “lead to the first new class of antibiotics in 30 years”.

Ishwar Singh, a drug discovery expert and senior lecturer in biochemistry at the University of Lincoln's School of Pharmacy, UK, is a co-author of the new study.

New drug clears infection in mice

Singh and colleagues studied the structure of teixobactin and found key amino acid substitutions that, when substituted, made the antibiotic more amenable to cloning into 10 synthetic analogues.

The team then tested these synthetic versions in test tubes. “These analogues exhibited potent antibacterial activity against Staphylococcus aureus, MRSA, and VRE,” the authors write.

Additionally, one of these analogues was found to be non-cytotoxic both in vitro and in vivo.

Further tests on mice – carried out by a team at the Singapore Eye Research Institute in Bukit Merah – showed that one of the analogues successfully treated a case of Staphylococcus aureus keratitis.

Specifically, use of the synthetic drug "reduced bacterial bioburden by more than 99% and significantly reduced corneal edema compared with untreated mouse corneas."

"Overall, our results established the high therapeutic potential of a teixobactin analogue in attenuating bacterial infections and associated severity in vivo," the researchers wrote.

“Leap Forward” in New Antibiotics

The significance of these findings is that when teixobactin was discovered, it was a breakthrough in itself as a new antibiotic that kills bacteria without causing resistance, including “superbugs” like MRSA, but natural teixobactin was not created for human use.

“There is still a significant amount of work to be done,” Singh says, “in developing teixobactin into a therapeutic antibiotic for humans. We are probably six to 10 years away from a drug that doctors can prescribe to patients.”

However, “this is a real step in the right direction and now opens the door to improving analogues in our bodies,” he said.

“The successful application of this simple synthetic version from the test tube to real-world cases is a qualitative leap forward in the development of new antibiotics and brings us closer to realizing the therapeutic potential of simple teixobactins.”

“Drugs that target the fundamental mechanisms of bacterial survival and also reduce the host inflammatory response are urgently needed,” concluded Rajamani Lakshminarayanan, of the Singapore Eye Research Institute.