With the rise of antibiotic-resistant "superbugs," the pressure is on for scientists to develop new molecules, materials and methods to keep us from returning to a dark age of medicine, where even the most basic of infections becomes potentially lethal. Now, researchers from Vanderbilt University have found a new class of antibiotic hiding in plain sight: human breast milk.

It's long been known that breastfeeding is a vital part of healthy development, with the milk providing a nutritious mix of proteins, fats and sugars. But it's not just about sustenance: since their immature immune systems leave infants vulnerable to infection, breast milk also serves to share the mother's immune function with her child. These antibacterial properties were mostly thought to come from the milk's proteins, but the Vanderbilt team set out to investigate if sugars also played a part.

"For most of the last century, biochemists have argued that proteins are most important and sugars are an afterthought," says Steven Townsend, director of the new study. "Most people have bought into that argument, even though there's no data to support it. Far less is known about the function of sugars and, as a trained glycoprotein chemist, I wanted to explore their role."

To test the antibacterial properties of the sugars, the team first extracted compounds called oligosaccharides from a few different samples of human breast milk. Using mass spectrometry, they created profiles of the compounds, and then introduced them to cultures of infectious bacteria – in this case, Group B Strep, a common culprit of infections in newborns.

On the left is a colony of strep bacteria, which clumps together to form a protective biofilm; on the right is a close up of that biofilm breaking down when exposed to human breast milk sugars(Credit: Steven Townsend/Vanderbilt)

In the first experiment, the team pitted five milk sugar samples against five strep colonies. While three of the samples didn't do a whole lot, one was moderately effective and one wiped out almost the whole bacterial colony. A second round of experiments is still ongoing, with the team testing more than two dozen samples. So far, two have been found to kill bacteria and destroy the biofilm that the bugs create to protect themselves, two more kill the bacteria without breaking down the biofilm and four others destroy the biofilm without killing the strep.

"Our results show that these sugars have a one-two punch," says Townsend. "First, they sensitize the target bacteria and then they kill them. Biologists sometimes call this 'synthetic lethality' and there is a major push to develop new antimicrobial drugs with this capability."

Even if the sugars aren't killing the bacteria, destroying the biofilm is still a useful strategy, allowing other antibacterial agents to come in and finish the job. To test this idea, the researchers combined the milk sugars with antimicrobial peptides found in human saliva, and then introduced that mix to strep cultures. Sure enough, the peptides had an easier time fighting the bugs when the milk sugars took down their defenses first.

Beyond strep, the researchers have found that the milk sugars were also effective against two of the six pathogens in the "ESKAPE" group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), a watchlist of the bacteria that are most rapidly evolving antibiotic resistance. The Vanderbilt research adds a new weapon to the arsenal against these superbugs, which should help infants and adults alike.

"This is the first example of generalized, antimicrobial activity on the part of the carbohydrates in human milk ," says Townsend. "One of the remarkable properties of these compounds is that they are clearly non-toxic, unlike most antibiotics."

The study was published in the journal Infectious Diseases, and the team describes the work in the video below.

Source: Vanderbilt University

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