Finding new drugs to treat life-threatening antibiotic-resistant infections is critical to human health, but only one new class – teixobactin – has been discovered in the last 33 years. The World Health Organization has labeled development of such drugs a high priority and in 2015, the Obama administration released an action plan to combat antibiotic-resistant bacteria.
Scientists trawling through thousands of soil samples have discovered a whole new class of antibiotics capable of killing drug-resistant bacteria. The chemical, which has been named malacidin, appears to be non-toxic in humans and is effective in tackling several multidrug-resistant bacteria such as Meticillin-resistant Staphylococcus aureus (MRSA), raising hopes that it could be used to develop new lines of treatment in the never-ending war against antibiotic-resistant pathogens.
The most effective antibiotic drugs so far have come from organisms in the environment that produce antibiotics naturally to defend against bacteria. For instance, penicillin was discovered from a fungus and vancomycin was found in bacteria that lives in dirt. Soil is a good place to look for antibiotics as it is an environment where multiple types of bacteria naturally compete for resources and use a range of exotic chemical compounds to kill each other.
“Environmental microbes are in a continuous antibiotic arms race that is likely to select for antibiotic variants capable of circumventing existing resistance mechanisms,” the authors wrote.
The malacidin chemical, identified by Dr Sean Brady and his laboratory at Rockefeller University, New York, works by attacking a fundamental step in bacterial growth, essentially interfering with a major building block that the bacteria use to build and repair their outer membrane. Initial tests showed that malacidin was not toxic to human cells, and did not induce resistance in S. aureus bacteria, even after 20 days. By comparison, bacteria in the lab have developed antibiotic resistance to the drug rifamycin in a single day.
In their study, published in the journal Nature Microbiology, the authors cautioned that it is only effective against gram-positive bacteria, species that have a very thick cell wall, and therefore, would not be effective against gram-negative bacteria. Nonetheless, the breakthrough suggests there may be more similar compounds like malacidin yet to be discovered in our natural environment.
Research on malacidin has just begun and bringing them to pharmacies will require years of additional research and clinical trials. “The ability to tap into the world’s microbiome in a systematic way could lead to the discovery of new natural products, which historically have been the most productive source of antibiotics so far,” said Brady.
It is also a promising sign that this new class follows closely after the 2015 discovery of teixobactin. Prior to that there had been a 30-year drought, prompting dire warnings of a post-antibiotic apocalypse if bacteria continued to adapt and develop resistance to antibiotics.
Asthma is a common inflammatory disease of the airways of the lungs, which varies largely in its severity and duration from person to person.
When exposed to certain asthma triggers (such as cold air, exercise, pollen and viruses), the sensitive airways of asthmatic individuals react. They can become red and inflamed, which causes the muscles to tighten and produce excess mucus. This causes the airways to get constricted and thereby severely reduce breath flow, thus triggering asthma.
Asthma is thought to be caused by a combination of genetic and environmental factors. Environmental factors include exposure to air pollution and allergens.
Common asthma symptoms include shortness of breath, wheezing, coughing, and a feeling of tightness in the chest. These episodes may occur a few times a day or a few times per week.
On one end, sufferers experience what is euphemistically termed as’ wheezing’, a milder cousin of asthma which can often be relieved by prescription beta-2 agonists such as salbutamol and corticosteroids taken via inhalation.
On the other extreme, full-blown asthma attacks can be life-threatening as severe shortness of breath restricts oxygen supply to the brain and other vital organs. Treatment in this case invariably involves hospitalization and intravenous administration of corticosteroids, in addition to nebulization until symptoms subside, and the patient is able to breathe well enough on his own.
Currently, there is no cure for asthma, and medical research into asthma has been largely focused on treatment rather than discovering means to cure or prevent it from occurring in the first place. Asthma was always known as a disease that can be largely controlled, but never cured.
New research led by Dr Pawan Sharma from the UTS School of Life Sciences and The Woolcock Institute of Medical Research, Australia seems set to create a precedent in the hitherto poorly researched field of asthma prevention.
Dr Sharma and a team of American researchers investigated whether the activation of bitter taste receptors could thwart the symptoms of asthma in mice.
They found that bitter substances not only reduced common symptoms of the disease in mice, but also prevented allergic inflammation and structural changes to the airways. This could be a game-changer for the 300 million people worldwide that live with asthma.
The research team induced mice with allergic asthma and tested the effects of chloroquine and quinine on various features of the disease. Chloroquine and quinine are substances that stimulate bitter taste receptors owing to their bitter taste. Both are used as anti-malaria drugs and as ingredients for tonic water, lending the latter its characteristic bitter taste.
When inhaled, these two compounds activated the taste-2 receptor protein (TAS2R). In doing so, they also block the allergic reaction in the lungs, thereby preventing asthma from occurring in the first place.
Past research has already shown that TAS2R agonists, compounds that activate the receptors, lead to relaxation in the airway of the lungs. But researchers hadn’t been able to test whether it was able to prevent the airway inflammation associated with asthma.
Excitingly, the spray didn’t just stop airway inflammation in the mice- it was also able to limit other characteristics of asthma, including mucus accumulation and associated structural changes to the airway.
The researchers confirmed these findings on human lung cells, finding that both chloroquine and quinine blocked the immune cells from reaching the airway, thereby limiting inflammation that could lead to an asthma attack.
“We used both in vitro and in vivo approaches using human airway cells and mouse models of asthma to study the effectiveness of novel bitter compounds. We do not have an effective anti-asthma therapy that targets disease progression. Our current research on taste receptors is crucial in identifying new classes of drugs that can be an effective asthma treatment option in future,” Dr Sharma said.
Dr Sharma is now preparing to collaborate with US researchers to synthesize new bitter compounds that may be developed as inhaled therapy for humans.
The possibility of a superbug spelling mankind’s doom, once the realm of gory science fiction, is fast becoming a horrifying reality with the rise of mankind’s worst nightmare: antibiotic-resistant superbugs.
Superbugs are bacteria or fungi that are resistant to two or more types of antibiotics, and consequently tougher to get rid off. Scientists warn that the day is not far off that one or more strains of superbugs might acquire immunity against even the most powerful of antibiotics in mankind’s arsenal. The threat is so dire that recently the United Nations declared superbugs a “fundamental threat” to global health.
The lethal Methicillin-resistant Staphylococcus aureus (MRSA) (Photo: Getty)
The misuse of antibiotics (such as taking them when you don’t need them or not completing a full prescribed course of antibiotic medicine) is the single leading factor contributing to this problem. The U.S. Centers for Disease Control and Prevention has released released a list of drug-resistant bacterial and fungal infections, labeling each as “urgent,” “serious” or “concerning,” on the basis of how dangerous they are, their prevalence, and difficulty of treatment.
Until now, the tried and tested method to combat superbugs was to develop even more powerful antibiotics, research into which has considerably slowed down since the 1980s.
However, while scientific research continued to explore how humans could stay ahead of bacteria, interest from drug companies dwindled because antibiotics, like all other drugs, are expensive to develop.
On average, pharmaceutical companies spend $5 billion in research and testing for each new drug they bring to the market. Because about 80 percent of the drugs emerging from labs fail in safety or efficacy testing, pharmaceutical companies need to recoup billions from each new drug that makes it to the market.
Unlike antibiotic drugs, which are increasingly losing their effectiveness in the long run with the rise of superbugs, pharmaceutical companies can make greater profits on drugs that can be used regularly without losing effectiveness- such as antidepressants, statins, and anti-inflammatory medications.
It is in light of this bleak scenario that the science world was caught unawares when a 25 year old PhD student just came up with a way to fight drug-resistant superbugs- withoutantibiotics.
Shu Lam, a Malaysian Chinese PhD student at the University of Melbourne in Australia, has developed a star-shaped polymer that can kill six different superbug strains without antibiotics, simply by ripping apart their cell walls.
“We’ve discovered that the polymers actually target the bacteria and kill it in multiple ways,” Lam told Nicola Smith from The Telegraph. “One method is by physically disrupting or breaking apart the cell wall of the bacteria. This creates a lot of stress on the bacteria and causes it to start killing itself.”
“Nowadays we already see a lot of people admitted to hospital or dying from bacterial infections that used to be quite easy to treat but aren’t anymore. What I’ve discovered is a class of new antimicrobial agents. We hope that these will be replacements for antibiotics,” says Shu Lam.
She believes her method of killing bacteria using tiny star-shaped molecules, built with short chains of protein units called peptide polymers, is a ground-breaking alternative to failing antibiotics.
Lam builds the star-shaped molecules at Melbourne’s prestigious school of engineering. Each star has 16 or 32 “arms” made from peptide polymers, a process she likens to putting together small blocks of Lego.
When unleashed, the polymers attack the superbugs directly, unlike antibiotics, which create a toxic swamp that also destroys nearby healthy cells.
Not only are they really good at killing superbugs, so far they’ve been relatively non-toxic to the body.
“Well, obviously we need to do more research to assess if these molecules have any other side-effects on the body, but currently, the preliminary results are showing that they kill the bacteria but not the healthy cells of the body,” Shu says.
Is this a game-changer?
Shu’s discovery is significant because it’s an alternative to antibiotics, not a new version of the same treatment.
So far, Lam has tested her star-shaped polymers on six strains of drug-resistant bacteria in the lab, and on one superbug in live mice.
In all experiments, they’ve been able to kill their targeted bacteria – and more significantly, unlike with conventional antibiotics, generation after generation of antibiotic-resistant bacteriadon’t seem to develop resistance to the polymers.
The polymers – which they call SNAPPs, or structurally nanoengineered antimicrobial peptide polymers – work by directly attacking, penetrating, and then destabilizing the cell membrane of bacteria.
Unlike antibiotics, which ‘poison’ bacteria, and can also affect healthy cells in the area, the SNAPPs that Lam has designed are so large that they can’t enter or affect healthy cells at all.
Lam hopes her “innovative” research will encourage pharmaceutical companies to invest. “I hope it will attract some interest, because what we have discovered is quite different from antibiotics,” she says.
“Some people have been telling me ‘Please work harder, so that we can have a solution and put it out on the market.’ But with research, you need to have a lot of patience because we still have quite a long way to go.”
Professor Greg Qiao, her PhD supervisor, says that Lam’s project is one of the biggest scientific breakthroughs he had seen in his 20 years at Melbourne university. But he cautions that it is still in its early stages, and will need at least another five years to develop, unless millions of pounds of investment can be found to speed the process. Cross-discipline work is still required to further reduce toxicity and work out the best way to administer the treatment, whether by tablet or injection.
Prof Qiao says: “The really good news about this is that, at the moment, if you have a superbug and you run out of antibiotics, there’s not much you can do. At least now, you can do something.”