Bacteriophages, Superbugs and the U.S. Soldier

Antibiotic resistance is one of the most pressing public health problems worldwide. Army scientists have developed a new weapon to combat superbugs that can protect soldiers and fight resistance.

Bacteriophages, a virus that infects and replicates within bacteria, kill bacteria through mechanisms different from antibiotics and can be targeted against specific strains. This makes them an attractive option for overcoming multidrug resistance. However, rapidly identifying and optimizing well-defined bacteriophages for use against a bacterial target is challenging.

Researchers at the MIT Institute for Soldier Nanotechnologies have found a way to achieve this. The U.S. Army established the Institute in 2002 as an interdisciplinary research center to dramatically improve the protection, survivability, and mission capabilities of soldiers and the platforms and systems that support them.

“This is a critical development in the fight against these superbugs,” said Dr. James Burgess, Program Manager, Institute for Soldier Nanotechnologies, Army Research Office, a member of the U.S. Army Combat Capabilities Development Command’s Army Research Laboratory. “The search for a cure for antibiotic-resistant bacteria is particularly important for soldiers deployed to parts of the world where they encounter unknown pathogens or even antibiotic-resistant bacteria. Wounded soldiers are even more vulnerable to infections, and they could bring these drug-resistant bugs home.”

In this study published in Cell, MIT bioengineers demonstrated that they can rapidly program bacteriophages to kill different E. coli strains by introducing mutations in a viral protein that binds to host cells. The results showed that these engineered bacteriophages are also less likely to induce resistance in bacteria.

“As we see more and more in the news, bacterial resistance continues to evolve and is becoming increasingly problematic for public health,” said Timothy Lu, MIT professor of electrical engineering and computer science and biological engineering and senior author of the study. “Phages represent an entirely different way of killing bacteria than antibiotics, which is complementary to antibiotics rather than trying to replace them.”

The researchers developed several genetically engineered phages that could kill laboratory-grown E. coli. One of the newly created phages was also able to eliminate two E. coli strains resistant to naturally occurring phages in a skin infection in mice.

The Food and Drug Administration has approved a handful of bacteriophages for killing harmful bacteria in food. However, they have not been widely used to treat infections to date, as it can be difficult and time-consuming to find naturally occurring phages that target the right type of bacteria.

To simplify the development of such treatments, Lu’s laboratory has been working on engineered viral scaffolds that can be easily adapted for different bacterial strains or different resistance mechanisms.

“We believe that phages are a good tool for killing and degrading bacteria in a complex ecosystem, but in a targeted manner,” Lu said.

The researchers wanted to find a way to accelerate the process of adapting phages to a specific type of bacteria. They developed a strategy that allows them to create and test a much larger number of tail fiber variants in a short time.

They generated phages with approximately 10 million different tail fibers and tested them against several E. coli strains that had proven resistant to the non-genetically modified bacteriophage. One way E. coli can become resistant to bacteriophages is by mutating LPS receptors so that they are truncated or absent. However, the MIT team found that some of its engineered phages can even kill E. coli strains with mutated or missing LPS receptors.

The researchers plan to apply this approach to other resistance mechanisms used by E. coli and to develop phages that can kill other types of harmful bacteria.

“The ability to selectively target these non-beneficial strains could provide us with many advantages in terms of clinical outcomes in humans,” Lu said.

Translation of source: http://outbreaknewstoday.com/bacteriophages-superbugs-and-the-us-soldier-29164/