Our Latest Weapon Against Antibiotic Resistance? Platypus Milk

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The platypus is, frankly, a weirdo. It’s one of the last surviving species of egg-laying mammals. It has venomous flippers. And that furry body combined with the duck bill? Looks like it belongs on evolution’s blooper reel.

And now another strange element of its biology is intriguing scientists: platypus milk contains a one-of-a-kind protein that could help us fight antibiotic resistance.

For nearly 70 years, antibiotics have been our go-to treatment option for a number of conditions, from gonorrhea to pneumonia. The more we’ve used them, the more resistant to antibiotics these bugs have become, resulting in some “superbugs” that don’t respond to several types of antibiotics.

That simple fact is putting millions of lives at risk every year in the U.S. alone. In 2016, the United Nations (UN) elevated the issue to “crisis level.” UN Secretary General Ban Ki-moon called it a “fundamental, long-term threat to human health, sustainable food production, and development.”

Scientists have gotten increasingly creative in their search for anything that might help humanity fight against antibiotic-resistant bacteria. In 2010, that led to the discovery that platypus milk contains antibacterial properties.

Unlike other mammals, which deliver milk to their young through teats, platypus “sweat” their milk, secreting it through the skin on their bellies for their young to drink. That leaves the offspring pretty exposed to the outside world, which may explain why platypus milk needs to contain antibacterial characteristics.

To find out exactly what makes the milk that way, a team of researchers from Australia’s Commonwealth Scientific and Industrial Research Organization (CSIRO) and Deakin University set out to replicate one of its proteins in a lab setting.

Once they got a closer look at the protein’s structure, they were surprised to see something completely unique. The three-dimensional fold made the protein look like a ringlet. So naturally the team dubbed the protein “Shirley Temple,” a reference to the actress’ curly hair.

The researchers believe this unique structure could help develop new drugs to take down superbugs. They’re looking for collaborators to help them do more research with the intention of hastening a new antibiotic to market.

And truly, we have no time to lose.

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A Synthetic Microbe Could Be the Next Antibiotic

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Drug-Resistant Superbugs

Antibiotic resistance is one of the main threats to public health of our time. While superbugs are emerging all over the world thanks to an overuse of existing antibiotics, particularly in agriculture and farming, new drugs able to fight increasingly potent infections are hard to come by.

To break this deadlock, researchers have been turning to synthetic molecules, which unlike common antibiotics can fight off infections without leading to drug resistance. Scientists at IBM Research, the world’s largest industrial research organization, have come up with a synthetic molecule that works as a last ditch effort against superbugs that have already spread to every organ in the body, travelling through the blood. Their findings are detailed in a new study published in the journal Nature Communications. 

Synthetic molecules, as the name implies, are lab designed and developed polymers, chemicals made of large molecules comprising smaller, simpler molecules. To be used as an antibiotic, a synthetic molecule has to meet certain conditions: It has to be biodegradable and able to effectively attack bacteria without endangering other organs in the body.

Usually, the immune system attacks bacteria by destroying their protective membranes, and IBM’s synthetic molecule had been designed to work the same way. “We are trying to emulate the exact way that our innate immune system works,” lead author James Hedrick explained to Popular Science. “When you get an infection, right away your body secretes antimicrobial peptides, which is simply a fancy word for a polymer.”

Works Better Than the Real Thing

The IBM research isn’t the first to explore the potential of synthetic molecules in fighting antibiotic resistance. One previous study focused on using synthetic molecules to prevent the genes carrying resistance properties from being transmitted between bacteria. Others use synthetic molecules as antibiotics that cause bacteria to explode, but researchers acknowledge that this is dangerous because it would help spread toxins in the bloodstream.

To minimize these side effects, IBM’s synthetic molecule works by killing the bacteria from the inside out. “First, the polymer binds specifically to the bacterial cell,” Hedrick wrote in an IBM Research blog. “Then, the polymer is transported across the bacterial cell membrane into the cytoplasm, where it causes precipitation of the cell contents (proteins and genes), resulting in cell death.”

How it kills superbugs. Image credit: Institute of Bioengineering and Nanotechnology

How it kills superbugs. Image credit: Institute of Bioengineering and Nanotechnology.

The molecules latch on to the bacteria using electrostatic charges to attach to various parts of their surface. So, even when a bacterium undergoes changes in its internal make-up, the synthetic polymers is still able to identify it.

The molecule is also able to completely degrade after three days. “It basically just comes in, kills the bacteria, degrades, and leaves,” Hedrick told Popular Science, adding that this approach could also mitigate antibiotic resistance or work against extremely resistant strains even when the bacteria has evolved.

So far, the IBM researchers have successfully tested their synthetic molecule on mice infected with five difficult-to-treat, multi-drug resistant superbugs that can be commonly acquired in hospitals and often lead to sepsis or even death. The plan is to eventually have the synthetic molecule ready for human clinical tests.

This research adds to the range of creative ideas scientists have come up with to stave off the worst impacts of the drug resistance crisis, including developing “super enzymes” to synthetic nanobots. Unfortunately, lab-produced molecules don’t come by as cheap as natural ones. For now, our best bet remains to always follow the doctor’s instructions and only use antibiotics only when we truly need them.

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Antibiotic Resistance Has Made Another Dangerous “Jump” Between Species

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Scientists are warning that the antibiotic resistance army has been joined by a new powerful enemy. For the first time, a team of researchers discovered that the gene responsible for drug resistance has spread to the bacteria Shigella flexneri, a main cause of potentially fatal diarrhea around the world.

In 2015, researchers discovered that the mcr-1 gene, which confers resistance to a “last resort” antibiotic called colistin, was spreading among pigs in Chinese farms via the gut bacteria Escherichia coli. Similar signs of resistance also emerged in farms in Denmark, France, the Netherlands and Thailand. For decades, antibiotics have been widely used in farming because they lessen disease risk, boosting animal growth and maximizing profits. Yet this practice has also made an increasing number of bacterial strains resistant to the agents designed to kill them off.

The latest research, published in the journal Applied and Environmental Microbiology, screened a sample of more than 2000 bacteria taken from animal feces on a farm, from patients, and from the environment in China. The team identified the mcr-1 gene on a transferable plasmid, a genetic element that can jump between bacterial species, carrying drug resistance with them — in this case, from S. flexneri to E. coli and potentially other bacterial strains too.

Already, the world is running out of effective antibiotics. Infections that were easily treatable just a few years ago might soon become deadly again, rolling back decades of medical progress and costing the lives of millions, particularly in developing countries.

To make things worse, developing new antibiotics is not a profitable business for pharma companies. The research pipeline is long and the final product is cheap and short-lived, as new antibiotics quickly become obsolete.

Pneumonia and tuberculosis are already spreading in a drug resistant form. Now diarrheal disease could add to the threat.

“This is concerning, as S. flexneri is the main cause of Shigella infections in low and middle income countries,” said coauthor Adam P. Roberts, a lecturer in Antimicrobial Chemotherapy and Resistance with the Liverpool School of Tropical Medicine, in a statement. Like drug-resistant tuberculosis, diarrhea caused by Shigella infections hits the developing world the most; annually, these infections already cause an estimated 1.1 million deaths, primarily in developing countries. Even so, antibiotic resistance can spread fast across the globe, including into wealthy countries like the United States.

“In order to try and control antimicrobial resistance, we need to understand the epidemiology of the resistance genes and how they move around,” Roberts said in the statement. “This work is part of that overall effort. Now that we know mcr-1 is functional and can transfer in Shigella we can monitor this situation to see if Shigella is responsible for transfer of this gene to other species.”

The study will help researchers understand new patterns of antibiotic resistance. But without developing new, more effective medicine, doctors won’t be able to stave off one of the biggest threats to public health of our time.

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Antibiotic Considered Obsolete May Find New Use Against Superbugs

Repurposing Antibiotics

The global public health threat of antibiotic resistance has made many existing antibiotic treatments ineffective, but a new study could provide a creative solution to the growing problem. In a study published in the journal Cell Chemical Biology, researchers from the University of Queensland in Australia re-analyzed an old and largely forgotten antibiotic. Discovered 40 years ago, the drug could potentially take on resilient superbugs.

Octapeptin has long been considered an obsolete antibiotic by medical science, but the researchers believe it could potentially replace a so-called “drug of last resort” called colistin. These are drugs given to patients only when all other treatment options have been exhausted without success. Over time, however, the bacteria colistin is meant to treat have developed increasing resistance to it, rendering the last resort ineffective. Researchers hope that octapeptin, a relic of past medicine though it may be, could be revived and reworked as a new drug.

In discussing the re-analysis of octapeptin, Matt Cooper from the University of Queensland in Australia said to Science Alert that “Given the very few researchers left in this field now, and the sparse pipeline for new antibiotics, we’ve used modern drug discovery procedures to re-evaluate its effectiveness against superbugs.”

Unique Solutions

Octapeptin is uniquely capable of serving as a replacement for colistin, primarily because the two drugs are structurally similar. Octapeptin has also been shown to be especially effective against gram-negative bacteria, a type of bacteria that are notoriously difficult to treat. In addition to its structural similarities and relative effectiveness, researchers believe octapeptin may prove to be superior to colistin, and even less toxic.

Over the last 30 years, antibiotic resistance has been of growing concern, reaching public health crisis levels in many parts of the world. Despite these urgent circumstances, only one new class of antibiotic has emerged. As such, the University of Queensland researchers are hoping that by re-analyzing the older antibiotic and introducing it as a superior alternative once colistin fails, they will at least have provided another weapon in our arsenal; potentially, a very powerful one. The team’s creative solution could also inspire other research that looks to repurpose old, forgotten about drugs — or even create brand new ones — that could be stockpiled for the ongoing fight against antibiotic resistance.

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Antibiotic Algorithm Will Fast-Track the Search for New Medicine

Hunting for Antibiotics

Antibiotic resistance is a growing issue in which harmful bacteria in the body are no longer receptive to the effects of antibiotics. Because of this issue, more and more patients struggle with everything from common illnesses to much more severe bacterial infections that could cause life-threatening harm.

One technique that could combat antibiotic resistance is finding variants of known antibiotics, or peptidic natural products (PNPs). Unfortunately, finding these variants has been an arduous and time-consuming process. Until now: a group of American and Russian computer scientists has created an antibiotic algorithm that, by rapidly sorting through databases, can discover 10 times more new variants of PNPs than all previous efforts combined.

The algorithm, known as VarQuest, is described in the latest issue of the journal Nature Microbiology. Hosein Mohimani, an assistant professor in Carnegie Mellon University’s Computational Biology Departmen, said in a press release that VarQuest completed a search that could have taken hundreds of years of computations traditionally.

Two packs of white circular pills, and two loose pills, on a rose-pink background. A new antibiotic algorithm will hopefully reduce resistance to traditional drugs like these.
Image Credit: padrinan / pixabay

Mohimani also said that the study expanded their understanding of the microbial world. Not only does finding more variants quickly increase researchers’ ability to formulate alternative antibiotics; it can also provide vital information to microbiologists.

“Our results show that the antibiotics produced by microbes are much more diverse than had been assumed,” said Mohimani in a press release.

Mohimani noted that, because VarQuest was able to find over one thousand variants and in such a short amount of time, it could give microbiologists a larger perspective, perhaps alerting them to trends or patterns that wouldn’t otherwise be noticeable.

Fighting Resistance

VarQuest’s success stands on the shoulders of computing progress made within the past few years. High-throughput methods have advanced, allowing samples to be processed in batches instead of one at a time, making the process much faster. Additionally, the effort has been supported by the Global Natural Products Social (GNPS) molecular network, launched in 2016. This is a database in which researchers from around the world collect data on natural products based on their mass spectra, the chemical analysis of how charge is distributed through a substance’s mass. Using this database alongside VarQuest could drastically enhance drug discovery abilities.

“Natural product discovery is turning into a Big Data territory, and the field has to prepare for this transformation in terms of collecting, storing and making sense of Big Data,” Mohimani said of this growing data and scientists’ ability to access it. “VarQuest is the first step toward digesting the Big Data already collected by the community.” 

What Are Algorithms?
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Every time a person consumes an antibiotic, evolution pushes bacterial species to develop resistance and multiply. Children and elderly adults have the highest rates of antibiotic use, but are also higher-risk groups to begin with, making this a particularly concerning issue with them. Many partially attribute the drastic growth of the resistance problem to the needless prescription of antibiotics to patients with viral illnesses, for whom antibiotics would have no effect but to create resistance.

This issue is only going to get worse if steps are not taken to prevent resistance in the first place. However, as solutions are crafted, working antibiotics are still needed for those facing both resistance and infection. This antibiotic algorithm will be a critical tool in mitigating the effects of resistance while also giving microbiologists a big-picture view, hopefully propelling research forward.

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Scientists Created a Synthetic Molecule, and It Could End Antibiotic Resistance

Transfer Prevention

Antibiotic resistance in bacteria, which includes both common bugs and so-called superbugs, is a serious and globally recognized problem. In fact, the United Nations elevated the issue to a crisis level almost a year ago now, and the World Health Organization (WHO) has stated that it’s rapidly worsening.

There are a multitude of possible responses to antibiotic resistance, and researchers from the Université de Montréal (UdeM) in Canada may have found another potential solution. In a study published in the journal Scientific Reports earlier this November, this team of researchers from UdeM’s Department of Biochemistry and Molecular Medicine explored a method that could block the transfer of antibiotic resistance genes.

The researchers focused on preventing a mechanism that allows for antibiotic resistance genes to be coded onto plasmids —which are DNA fragments that can carry genes that encode the proteins that render bacteria drug-resistant. Concretely, they found the exact binding sites for these proteins, which are essential in plasmid transfer. This allowed them to design more potent chemical molecules which reduce the transfer of gene-carrying, antibiotic-resistant plasmids.

“You want to be able to find the ‘soft spot’ on a protein, and target it and poke it so that the protein cannot function,” Christian Baron, the vice-dean of R&D at UdeM’s faculty of medicine, said in a press release. “Other plasmids have similar proteins, some have different proteins, but I think the value of our study on TraE is that by knowing the molecular structure of these proteins we can devise methods to inhibit their function.”

A Deadly Problem

The effects of antibiotic resistant bacteria are pretty much self-explanatory. Antibiotics remain a critical piece of modern medicine, and when they become ineffective, what we’re left with are disease-causing superbugs that are much more difficult to treat and manage. Antibiotics are also used as prophylactic treatment during surgeries as well as in cancer therapies.

According to a report by a special commission set up in the United Kingdom in 2014 called the Review on Antimicrobial Resistance, drug-resistant bacteria could take the lives of some 10 million people by 2050. This isn’t particularly difficult to imagine since antibiotic-resistant bacteria infect 2 million people in the U.S. alone every year, according to the Centers for Disease Control and Prevention (CDC), and at least 23,000 of these cases are fatal. Additionally, the WHO reports that there are about 480,000 of multi-drug resistant tuberculosis cases around the world every year.

In short, antibiotic resistance is a problem we need to solve as soon as possible, starting now. Thankfully, there are a number of groups working on the issue, with a variety of approaches. Some have used CRISPR gene-editing to engineer synthetic nanobots that specifically target antibiotic-resistant bacteria and there are even efforts to employ “super enzymes” to fight off superbugs. Meanwhile, others like the UdeM researchers are focusing on a better understanding of how bacteria work to develop methods to render them more susceptible to antibiotics.

The CDC has already invested more than $ 14 million to fund research into antibiotic resistance, and we might soon see these efforts come to fruition. This will take time, obviously, but it could help to liven up the pace by which new drugs are produced. As Baron said, “[p]eople should have hope. Science will bring new ideas and new solutions to this problem. There’s a big mobilization now going on in the world on this issue. I wouldn’t say I feel safe, but it’s clear we’re making progress.”

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New Research Shows Asymmetry in Bacteria Might Help Us Fight Antibiotic Resistance

Membrane Vacuum Cleaner

In the ongoing war to defeat antibiotic resistance, a new study has identified a protein that acts as a “membrane vacuum cleaner” — an attribute that means it could serve as a new target for antibiotics. The research indicates that the process of purging the outer membrane of gram-negative bacteria of specific lipids (which requires a particular protein) might be a vulnerability drugs could target. More specifically, antibiotics could possibly enhance their existing effectiveness by using the protein researchers identified, or even decrease the virulence of many common bacteria such as E coli.

Gram-negative bacteria have two membranes — one inner and one outer. This new research implicates the outer rather than the inner membrane. The outer membrane is an asymmetrical bilayer composed of inner and outer leaflets. The inner leaflet is made up of phospholipids, and the outer leaflet is made up of mostly lipopolysaccharides, which create a sugar-coated surface that efficiently excludes hydrophobic molecules and resists antibiotics — as well as other compounds that might endanger the bacteria.

However, the outer leaflet requires a cleaning system, because phospholipids from the inner leaflet accumulate inside it creating “islands” that render the outer membrane more permeable to toxic compounds. This, in turn, makes the entire bacterium more vulnerable.

The asymmetry and permeability barrier of the outer membrane must be restored in order to keep the bacterium healthy, which means those phospholipid molecules must be removed. This is the job of the maintenance of lipid asymmetry (Mla) system, which most Gram-negative bacteria have. The focus of the recent research is the MlaA protein, a component of the Mla system.

Newcastle University Professor of Membrane Protein Structural Biology and lead author Bert van den Berg explained in a press release: “Our three-dimensional structures and functional data show that MlaA forms a donut in the inner leaflet of the outer membrane. This binds phospholipids from the outer leaflet and removes these via the central channel, somewhat similar to a vacuum cleaner.”

Image Credit: Bert van den Berg/Newcastle University

The Threat of Antibiotic Resistance

The researchers plan to continue to study the MlaA protein as a target for antibiotics. This work is essential, as the development of new drugs is being outpaced by antibiotic resistance. As such, many researchers have pivoted to focusing bacteria themselves; in space, in nature, and even at the nanoscale for quantum effects. Researchers are also working to attack antibiotic resistance at the chemical and molecular level, searching for the genetic roots of resistance, using CRISPR and otherwise preventing expression of genes that enable resistance. The issue itself is at a crisis point, according to authorities like the World Health Organization, the Centers for Disease Control, and the United Nations.

This new research will aid in our ongoing fight against this critical issue. Professor van den Berg commented in the release, “Our study illuminates a fundamental and important process in Gram-negative bacteria and is a starting point to determine whether the Mla system of Gram-negative pathogens could be targeted by drugs to decrease bacterial virulence, and to make various antibiotics more effective.”

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The Development of New Drugs Isn’t Matching the Pace of Antibiotic Resistance

Dwindling Resources

Last year, the United Nations raised the issue of antibiotic-resistant bacteria to crisis level, calling the situation “a fundamental, long-term threat to human health, sustainable food production, and development.” Now, the World Health Organization (WHO) is reporting that not nearly enough new antibiotics are in development to replace those that are now ineffective.

Bioprinting: How 3D Printing is Changing Medicine
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In their newly published report, the organization notes that only 51 new antibiotics and 11 biologicals are in clinical development. Only 33 of those target the “priority pathogens” identified by the WHO last year. These pathogens are showing an increased immunity against current drugs, and they can be deadly — tuberculosis alone is responsible for more than 250,000 deaths each year.

Of those 33 antibiotics in development, only eight are said to be innovative in a way that will be beneficial. The other 25 are tweaks to existing treatments that are, ultimately, short-term solutions. Additionally, the WHO reports that very few oral antibiotics, which are vital to treating infections outside of hospitals in low- or middle-income nations, are in development.

Fighting Back

Dr. Tedros Adhanom Ghebreyesus, Director-General of WHO, laid out the situation in a statement: “There is an urgent need for more investment in research and development for antibiotic-resistant infections including [tuberculosis], otherwise we will be forced back to a time when people feared common infections and risked their lives from minor surgery.”

Thankfully, the WHO is doing something to combat this issue. They’ve partnered with the Drugs for Neglected Diseases Initiative (DNDi) to set up the Global Antibiotic Research and Development Partnership (GARDP). The goal of that collaboration is to gather funding for the research and development of new antibiotics that bacteria and other diseases have yet to build an immunity to.

According to Dr. Mario Raviglione, Director of the WHO Global Tuberculosis Program, new tuberculosis treatments are particularly needed. “Research for tuberculosis is seriously underfunded, with only two new antibiotics for treatment of drug-resistant tuberculosis having reached the market in over 70 years,” said Raviglione. “If we are to end tuberculosis, more than US$ 800 million per year is urgently needed to fund research for new antituberculosis medicines.”

New medicines alone won’t be enough, however — we also need to improve infection prevention and control. To that end, the WHO is creating a series of guidelines that will hopefully ensure better use of antibiotics in the human, animal, and agricultural sectors. When combined, these various efforts, and others like them, are our best hope for fighting the superbugs currently plaguing the world’s population.

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