Taming pathogens with mucus and phages

Millions of people are treated with antibiotics each year for infections or as a preventative measure. The Centers for Disease Control and Prevention reports that at least 2.8 million people are infected with antibiotic-resistant bacteria each year, meaning the germs have found ways to overpower antibiotics and continue to grow. Treating antibiotic-resistant infections is costly and time-intensive. Two teams of NIBIB-funded scientists have been working to find alternative solutions for treating bacterial infections, especially antibiotic-resistant bacteria.

How does your runny nose fight bacteria?

A runny nose isn't the only place mucus exists in our bodies; it also lines many passageways, like the digestive system, to keep them lubricated. Massachusetts Institute for Technology (MIT) researchers have found that sugars in mucus help control and disarm pesky microbes in our bodies. Most people think the slimy substance is a nuisance and gross, but it plays a vital role in many bodily systems.

Mucins, the gel-forming component in mucus, are coated in glycans, or sugars, and have been known to suppress the formation of biofilm, a microbial growth form that is often associated with infections and difficult to treat with antibiotics. This study, published in Nature Microbiology, finds a broader range of functions for the glycans attached to mucins. Researchers think they may not need to actually kill the pesky microbes, but instead, disarm them and render them less infectious.

Antibiotics are becoming less effective against fast-adapting bacteria. We need to leverage naturally--occurring defense mechanisms to protect ourselves from microbes."David Rampulla, Ph.D., director of the NIBIB Biomaterials and Biomolecular Constructs program

Mucus is densely packed with harmful microbes, so how does the body use this slimy substance to prevent infections? One would think something in mucus may kill the bacteria. The MIT team, led by Katharina Ribbeck, Ph.D., Professor in the Biological Engineering Department, has found that mucus tames pathogens contained in its sticky matrix so the immune system can kick in and fight when it needs to-;but mucus doesn't kill bacteria on its own.

Many used to think the structural network of mucus was purely for mechanical purposes, but we've learned it plays a critical role in the way it controls problematic pathogens as well. We are testing to see if this function is universal across many species."Katharina Ribbeck, Ph.D., Professor in the Biological Engineering Department, MIT 

The researchers dissected the different parts of mucus and found that the key ingredient that tamed bacteria was glycans. Glycans are chains of sugar molecules that form branched structures. The researchers questioned if the glycans would have the same power without the other components in mucus. Results confirmed that the glycans are robust at defusing pathogens on their own.

This study focused on the glycans' response to a specific bacterium, P. aeruginosa, that causes infections in people with a compromised immune system. Graduate student, Kelsey Wheeler, found the glycans made the bacteria less potent by suppressing genetic pathways responsible for bacterial communications and ones that allow clumping or toxin production. These pathways enable their infectious behavior.

Ribbeck said one of her greatest challenges has been convincing people that mucus is worth studying and not just a waste product. "We can create alternative therapeutic approaches that don't use antibiotics to kill microbes, but instead use nature's form of biological engineering – mucus," said Ribbeck.

Up next for Ribbeck is to break the glycan code and understand which glycans tame a specific pathogen and how they bind together. She also wants to learn more about if and how microbes can sense glycans and consequently try to escape them. Many different types of bacteria coexist in communities inside our bodies and, in part, make up a person's microbiome, which plays an essential role in digestion and immune health. Ribbeck thinks glycans play a significant part in maintaining and altering the microbiome in our bodies, and her lab is beginning to test the theory.

Manufacturing viruses to fight antibiotic-resistant bacteria

Timothy Lu, Ph.D., an MIT Associate Professor in the Department of Biological Engineering and Electrical Engineering and Computer Science, has been working on another alternative approach to treating antibiotic-resistant bacterial infections. Lu has been developing a way to engineer a special type of virus called a bacteriophage or phage to kill different strains of E. coli.

Antibiotics typically inhibit or regulate enzymes that are responsible for controlling the growth and spread of bacteria, giving the immune system time to fight infections. Phages kill bacteria through a different mechanism. Most commonly, phages recognize a specific receptor on a bacterium that allows them to bind and inject their virus into the bacteria. The virus will replicate and eventually kill the bacteria.

"Using phages to treat antibiotic-resistant infections is not a new concept," said Lu. He explained that one could perform an extensive, timely screen to identify naturally occurring phages that kill specific types of bacteria. "But at the end of the screen, you will likely be left with a diverse group of phages that will be difficult to manufacture and scale-up in a commercially reproducible, cost-effective way."

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Common foods alter gut bacteria by influencing viruses

In science today, food and gut bacteria are two topics that are guaranteed to fuel interest and debate. Both, of course, are interrelated, and a new study focuses on some subtleties of this relationship.

The lack of a healthy population of gut bacteria compromises our health; the same is true when we do not eat a healthful diet. However, scientists do not entirely understand the exact impact of specific foods on gut bacteria.

This knowledge gap is due, in part, to the unbelievable complexity of the microbiome. One factor that muddies the water is bacteriophages, or phages for short.

The phage

Phages are viruses that only attack bacteria. Within the gut, these viruses outnumber the dizzyingly numerous gut bacteria.

Each phage only attacks a specific type of bacterium, meaning that it can influence levels of gut bacteria. Phages need bacteria to live, so if bacteria are absent, the phages cannot survive.
This means that any foods that influence phages can influence gut bacteria and vice versa. For example, if the population of one type of phage increases, the bacteria that they consume will dwindle, potentially making room for another species of bacteria to multiply.

In this way, viruses can affect the overall microbiome — by pruning one species, they provide space for other species to fill.

Switching from prophage

Most phages in the gut are present in a dormant form — their DNA is integrated into the bacteria's genome. In this form, they are called prophages.

Scientists have identified certain compounds that trigger prophages to return to their active form. When this happens, hundreds of new phages burst out of the bacterial cell, killing the host and attacking other bacteria; these compounds include soy sauce, nicotine, and some antibiotics, such as ciprofloxacin. To date, the list of phage-promoting compounds is relatively short.

It is essential to uncover which chemicals fuel phage activity. Because phages attack and kill bacteria, if we understand how to manipulate them, they could work as powerful, natural antibiotics.

A recent study set out to expand the list of compounds that induce phage activity. The scientists from San Diego State University, CA, published their findings in the journal Gut Microbes. They hope that their results will introduce the "possibility of using diet to intentionally landscape the human gut microbiome via prophage induction."

"We could actually tackle certain conditions by adjusting the foods we consume that will affect microbial diversity, which in turn will influence health and diseases."  Research associate Lance Boling

To investigate, the researchers chose a wide range of compounds that might influence phage activity. They selected a range of bacteria from two phyla that are common in the gut: Bacteroidetes and Firmicutes. They included both beneficial and pathogenic strains of bacteria.

From 117 food compounds, they narrowed down their search to just 28. The researchers observed the growth of bacteria in the presence of each specific compound; they also observed its growth without the compound as a control. Next, they used flow cytometry, a process that is sensitive enough to detect unimaginably small virus particles.

Which foods influence phages?

Of the 28 candidates, 11 compounds produced levels of virus particles at a rate higher than the controls, which signifies that they influenced phage activity.

Some of the most significant phage boosts occurred in the presence of clove, propolis (a compound produced by bees), uva ursi (also known as kinnikinnick or bearberry), and aspartame.

Conversely, some foods reduced the number of virus particles; most notably, these included rhubarb, fernet (a type of Italian liquor), coffee, and oregano.

To complicate matters, some compounds boosted phage activity associated with some bacteria, but reduced phage activity related to others; these compounds include toothpaste, grapefruit seed extract, and pomegranate.

According to the authors, one of the most potent antibacterial foods was hot tabasco sauce, which "reduced the growth of all three [gastrointestinal] species, except the opportunistic pathogen P. aeruginosa, by an average of 92%."

Tabasco contains vinegar, but when they tested vinegar alone, it only reduced bacterial growth by 71%. They believe that capsaicin — the spicy compound in chilis — may explain the additional antibacterial capabilities. However, in the experiments with tabasco, no virus particles were found, so phages are unlikely to be involved.

The future

These findings are important. Scientists now know that the microbiome can influence our physical and mental health; it can also cause inflammation and increase cancer risk. If scientists can work out how to alter the microbiome in specific ways, they can, in theory, remove or reduce these risks.

As one of the authors, Forest Rohwer, explains, "The ability to kill specific bacteria, without affecting others, makes these compounds very interesting."

The new list of compounds is by no means exhaustive, of course, as Rohwer says, "There are probably thousands of compounds that would be useful for eliminating unwanted bacteria."

The authors hope that scientists will continue along these lines. They also explain that scientists will need to try to figure out the molecular mechanisms that switch the phage from inactivity to activity.

This is only for your information, kindly take the advice of your doctor for medicines, exercises and so on.     
https://gscrochetdesigns.blogspot.com. one can see my crochet creations  
https://gseasyrecipes.blogspot.com. feel free to view for easy, simple and healthy recipes    
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