Metallodrug Effective in “Taming” Antibiotic Resistant Superbugs

Metallodrugs are pharmaceuticals that use metal as an active ingredient, and according to the research, this one is able to substantially reduce the dangerous advancement of antibiotic resistance. More hospitals and medical researchers should therefore know about this.

Antimicrobial resistance posed by “superbugs” has been a major public health issue of global concern. Drug-resistant infections kill around 700,000 people worldwide each year. The figure could increase up to ten million by 2050, exceeding the number of deaths caused by cancers, according to figures of the World Health Organization (WHO).

Current clinical options for treating antibiotic resistant infections include increasing the prescribed antibiotic dose or using a combination therapy of two or more antibiotics. This might potentially lead to overuse of antibiotics, producing superbugs more resistant to antibiotics. Nevertheless, the development of antibiotic resistance far outruns the approvals of new antibacterial agents. While it may take a decade and cost an unusual high investment of USD 1 billion in average to bring a new drug to market, generating resistance to a new drug only requires a short couple of years by bacteria. Scientists and clinicians are in desperate need to discover an economic, effective, safe alternative strategy to meet the global public health challenge of antimicrobial resistance.

A research team led by Professor Sun Hongzhe of the Department of Chemistry, Faculty of Science and Dr Richard Kao Yi-Tsun of the Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong (HKU) discovered an alternative strategy by repositioning colloidal bismuth subcitrate (CBS), an antimicrobial drug against Helicobacter pylori (H. pylori) -related ulcer.

They found the bismuth-based metallodrug to effectively paralyze multi-resistant superbugs, e.g. Carbapenem-resistant Enterobacteriaceae (CRE) and Carbapenem-resistant Klebsiella pneumoniae (CRKP) and significantly suppress the development of antibiotic resistance, allowing the lifespan of currently-used antibiotic to be largely extended. CRE and CRKP can cause deadly infections such as bacteremia, pneumonia, and wound infections.

The team is the first globally to link the “resistance-proof” ability of metallo-drug to the treatment of superbugs. This bismuth drug-based therapy looks set to become the last-line strategy against superbugs infections apart from development of new antibiotics. Since CBS is a US Food and Drug Administration (FDA)-approved drug, it will hopefully be rapidly ready for human clinical trials.

[…]

More importantly, the brand-new therapy allows the dose of antibiotics to be reduced by 90% to attain the same level of effectiveness, and the development of NDM-1 resistance to be significantly slowed down, which will largely extend the life cycle of currently used antibiotics.

In the mouse model of NDM-1 bacterial infection, combination therapy comprising CBS and Carbapenem significantly prolonged the life expectancy and raised the eventual survival rate of infected mice by more than 25 percentage points compared to Carbapenem monotherapy. The research team now concentrates on using CBS-based therapy in other animal infection models, e.g. urinary tract infection (UTI), hoping to offer a more extensive approach to combat with antibiotic resistant superbugs.

Dr Ho found the results very encouraging, he said: “There is currently no effective approach to overcome the NDM superbug. Bismuth has been used clinically for decades. Knowing that it can tame the NDM is like “a good rain after a long drought” for the scientific community.”

CDC Warning About Resistant “Nightmare Bacteria” Appearing in the U.S.

Antimicrobial resistance is among the most important issues facing society today, and it’s somewhat unnerving that there’s such a lack of focus on it. There needs to be a massive new funding effort to develop new ways to fight this threat.

You’ve probably read about antibiotic resistance at some point, but sometimes it’s hard to stress just how important this issue is, especially when it feels like a far off problem.

So how about this – each year, over 23,000 Americans die because of bacteria that is resistant to antibiotics.

According to a new study from the Centers for Disease Control and Prevention (CDC), last year, nationwide tests discovered 221 instances of ‘unusual’ germs – bugs resistant to all, or most antibiotics tested on it.

This is no longer a far-off problem – it’s something hospitals are fighting right now.

“Unusual resistance germs, which are resistant to all or most antibiotics tested and are uncommon or carry special resistance genes, are constantly developing and spreading,” the CDC team writes for their in-house journal, Vital Signs.

“Lab tests uncovered unusual resistance more than 200 times in 2017 in “nightmare bacteria” alone.”

Nightmare bacteria are bacteria that are either nearly, or fully untreatable.

The study found that one in four samples sent into the lab for testing had bacteria with special genes that allowed them to spread resistance to other bacteria.

Not only that, but in facilities that had these bacteria with unusual genes, about 1 in 10 symptomless people who were screened had at least one resistant bug.

These people can pass on the resistant bacteria, effectively becoming a silent carrier of an illness.

“CDC’s study found several dangerous pathogens, hiding in plain sight, that can cause infections that are difficult or impossible to treat,” said CDC Principal Deputy Director Anne Schuchat.

So, what can we do? Many researchers are working on developing more antibiotics, or ways of stopping bacteria without antibiotics, but the CDC is urging hospitals and healthcare providers to stay on top of the problem as well.

“As fast as we have run to slow [antibiotic] resistance, some germs have outpaced us,” Schuchat said to Kaiser Health News.

“We need to do more and we need to do it faster and earlier.”

The paper recommends rapid identification of bacteria to check for resistance, completing infection control assessments, and testing those without symptoms who may also carry and spread the germs.

This is on top of the advice already provided by the CDC to do with correct use to antibiotics, both in prescribing, and taking them – for example, not using antibiotics when you have a viral infection like the common cold or the flu.

But there is some good news as well – the CDC lab network “is working at an absolutely high level of effectiveness,” said William Schaffner, from the Vanderbilt University School of Medicine to Kaiser Health News.

Possible Biological Solution to Carbon Capture/Recycling

Carbon capture remains an important goal for fighting off climate change.

Scientists at the University of Dundee have discovered that E. coli bacteria could hold the key to an efficient method of capturing and storing or recycling carbon dioxide.

Cutting carbon dioxide (CO2) emissions to slow down and even reverse global warming has been posited as humankind’s greatest challenge. It is a goal that is subject to considerable political and societal hurdles, but it also remains a technological challenge.

New ways of capturing and storing CO2 will be needed. Now, normally harmless gut bacteria have been shown to have the ability to play a crucial role.

Professor Frank Sargent and colleagues at the University of Dundee’s School of Life Sciences, working with local industry partners Sasol UK and Ingenza Ltd, have developed a process that enables the E. coli bacterium to act as a very efficient carbon capture device.

Professor Sargent said, “Reducing carbon dioxide emissions will require a basket of different solutions and nature offers some exciting options. Microscopic, single-celled bacteria are used to living in extreme environments and often perform chemical reactions that plants and animals cannot do.

“For example, the E. coli bacterium can grow in the complete absence of oxygen. When it does this it makes a special metal-containing enzyme, called ‘FHL’, which can interconvert gaseous carbon dioxide with liquid formic acid. This could provide an opportunity to capture carbon dioxide into a manageable product that is easily stored, controlled or even used to make other things. The trouble is, the normal conversion process is slow and sometime unreliable.

“What we have done is develop a process that enables the E. coli bacterium to operate as a very efficient biological carbon capture device. When the bacteria containing the FHL enzyme are placed under pressurised carbon dioxide and hydrogen gas mixtures — up to 10 atmospheres of pressure — then 100 per cent conversion of the carbon dioxide to formic acid is observed. The reaction happens quickly, over a few hours, and at ambient temperatures.

“This could be an important breakthrough in biotechnology. It should be possible to optimise the system still further and finally develop a `microbial cell factory’ that could be used to mop up carbon dioxide from many different types of industry.

“Not all bacteria are bad. Some might even save the planet.”

Not only capturing carbon dioxide but storing or recycling it is a major issue. There are millions of tonnes of CO2 being pumped into the atmosphere every year. For the UK alone, the net emission of C02 in 2015 was 404 million tonnes. There is a significant question of where can we put it all even if we capture it, with current suggestions including pumping it underground in to empty oil and gas fields.

“The E. coli solution we have found isn’t only attractive as a carbon capture technology, it converts it into a liquid that is stable and comparatively easily stored,” said Professor Sargent.

“Formic acid also has industrial uses, from a preservative and antibacterial agent in livestock feed, a coagulant in the production of rubber, and, in salt form, a de-icer for airport runways. It could also be potentially recycled into biological processes that produce CO2, forming a virtuous loop.”

Bacteria Can Acquire Antibiotic Resistance from Rival Bacteria, New Research Proves

It seems as though this is really important research into antibiotic resistance, as new metrics based on this research will need to be used to evaluate the dangerousness of antibiotic resistant bacteria in the future. The World Health Organization has said that “antimicrobial resistance is a global health emergency,” and reports for years have warned of the trillions of dollars and millions of lives that could be lost if this antibiotic resistance problem isn’t addressed.

Bacteria not only develop resistance to antibiotics, they also can pick it up from their rivals. Researchers have demonstrated that some bacteria inject a toxic cocktail into their competitors causing cell lysis and death. Then, by integrating the released genetic material, which may also carry drug resistance genes, the predator cell can acquire antibiotic resistance.

The frequent and sometimes careless use of antibiotics leads to an increasingly rapid spread of resistance. Hospitals are a particular hot spot for this. Patients not only introduce a wide variety of pathogens, which may already be resistant but also, due to the use of antibiotics to combat infections, hospitals may be a place where anti-microbial resistance can develop and be transferred from pathogen to pathogen. One of these typical hospital germs is the bacterium Acinetobacter baumannii. It is also known as the “Iraq bug” because multidrug-resistant bacteria of this species caused severe wound infections in American soldiers during the Iraq war.

Multidrug-resistant bacteria due to gene exchange

The emergence and spread of multidrug resistance could be attributed, among other things, to the special skills of certain bacteria: Firstly, they combat their competitors by injecting them with a cocktail of toxic proteins, so-called effectors, using the type VI secretion system (T6SS), a poison syringe. And secondly, they are able to uptake and reuse the released genetic material. In the model organism Acinetobacter baylyi, a close relative of the Iraq bug, Prof. Marek Basler’s team at the Biozentrum of the University of Basel, has now identified five differently acting effectors. “Some of these toxic proteins kill the bacterial competition very effectively, but do not destroy the cells,” explains Basler. “Others severely damage the cell envelope, which leads to lysis of the attacked bacterium and hence the release of its genetic material.”

The predator bacteria take up the released DNA fragments. If these fragments carry certain drug resistance genes, the specific resistance can be conferred upon the new owner. As a result, the antibiotic is no longer effective and the bacterium can reproduce largely undisturbed.

Pathogens with such abilities are a major problem in hospitals, as through contact with other resistant bacteria they may accumulate resistance to many antibiotics — the bacteria become multidrug-resistant. In the worst case, antibiotic treatments are no longer effective, thus nosocomial infections with multidrug-resistant pathogens become a deadly threat to patients.

Toxic proteins and antitoxins

“The T6SS, as well as a set of different effectors, can also be found in other pathogens such as those which cause pneumonia or cholera,” says Basler. Interestingly, not all effectors are sufficient to kill the target cell, as many bacteria have developed or acquired antitoxins — so-called immunity proteins. “We have also been able to identify the corresponding immunity proteins of the five toxic effectors in the predator cells. For the bacteria it makes absolute sense to produce not only a single toxin, but a cocktail of various toxins with different effects,” says Basler. “This increases the likelihood that the rivals can be successfully eliminated and in some cases also lysed to release their DNA.”

Conquest of new environmental niches

Antibiotics and anti-microbial resistance have existed for a long time. They developed through the coexistence of microorganisms and enabled bacteria to defend themselves against enemies or to eliminate competitors. This is one of the ways in which bacteria can conquer and colonize new environmental niches. With the use of antibiotics in medicine, however, the natural ability to develop resistance has become a problem. This faces researchers with the challenge of continually developing new antibiotics and slowing down the spread of drug resistance.

Baby Formula Made by French Corporation Lactalis Recalled Worldwide Over Possible Salmonella Contamination

Salmonella affects millions of people every year.

Nearly 7,000 tons” of baby milk formula made by the French company Lactalis has been recalled over fear of salmonella contamination.

The recall affects all products made at a factory in Craon in northwest France since February 15, 2017, including some meant for export to Britain, China, Greece, Haiti, Colombia, and Peru, among other countries.

After 20 cases of salmonella were reported in early December among French children younger than six months old, 12 Lactalis products were recalled in the country. Upon the discovery of five additional cases of salmonella, the DGCCRF, a consumer-protection agency in France, ordered the expansion of the recall. The full list of recalled products, which includes brand names such as Milumel, Celia, and Picot, is available from DGCCRF’s website.

Though the recall does not appear to affect U.S. consumers, it may affect American businesses. A melamine contamination that killed six children in China led to improved business for American baby food exporters as consumers lost faith in domestic producers.

Lactalis is the world’s largest dairy company with global sales of 17 billion euros ($20 billion) in 2015. Its American subsidiary, Lactalis American Group, produces a number of popular cheese brands, including Président, Sorrento, Precious, Rondelé, and Galbani. These brands are not part of the recall.

Scientists Discover Flies Carry More Diseases Than Suspected

The diseases linked to the several hundred bacteria flies were found to carry include pneumonia and stomach bugs. Be careful clicking the link if you’d rather not look at closer images of flies.

An important point here though is to remember this when there are flies buzzing around someone precious to you with fragile health. Losing someone close to you can truly be a very unfortunate experience.

The house fly and the blowfly together harbour more than 600 different bacteria, according to a DNA analysis.

Many are linked with human infections, including stomach bugs, blood poisoning and pneumonia.

Flies can spread bacteria from place-to-place on their legs, feet and wings, experiments show. In fact, every step taken by a fly can transfer live bacteria, researchers said.

”People had some notion that there were pathogens that were carried by flies but had no idea of the extent to which this is true and the extent to which they are transferred,” Prof Donald Bryant of Penn State University, a co-researcher on the study, told BBC News.

DNA sequencing techniques were used to study the collection of microbes found in and on the bodies of the house fly (Musca domestica) and the blowfly (Chrysomya megacephala).

The house fly, which is ubiquitous around the world, was found to harbour 351 types of bacteria. The blowfly, which is found in warmer climates, carried 316. A large number of these bacteria were carried by both types of fly.

The researchers, who published their study in the journal Scientific Reports, say flies may have been overlooked by public health officials as a source of disease outbreaks.

“We believe that this may show a mechanism for pathogen transmission that has been overlooked by public health officials, and flies may contribute to the rapid transmission of pathogens in outbreak situations,” said Prof Bryant.

Treatment Against Antibiotic-Resistant Superbugs Can be Increased Through Nanoparticles

The effectiveness of antibiotic treatments for antibiotic-resistant superbugs can be increased through nanoparticles activated by light, which are also known as quantum dots. This research represents an important development in the fight against antibiotic resistance.

Multi-drug resistant pathogens, which evolve their defenses faster than new antibiotic treatments can be developed to treat them, cost the United States an estimated $20 billion in direct healthcare costs and an additional $35 billion in lost productivity in 2013.

CU Boulder researchers, however, were able to re-potentiate existing antibiotics for certain clinical isolate infections by introducing nano-engineered quantum dots, which can be deployed selectively and activated or de-activated using specific wavelengths of light.

Rather than attacking the infecting bacteria conventionally, the dots release superoxide, a chemical species that interferes with the bacteria’s metabolic and cellular processes, triggering a fight response that makes it more susceptible to the original antibiotic.

“We’ve developed a one-two knockout punch,” said Prashant Nagpal, an assistant professor in CU Boulder’s Department of Chemical and Biological Engineering (CHBE) and the co-lead author of the study. “The bacteria’s natural fight reaction [to the dots] actually leaves it more vulnerable.”

The findings, which were published today in the journal Science Advances, show that the dots reduced the effective antibiotic resistance of the clinical isolate infections by a factor of 1,000 without producing adverse side effects.

“We are thinking more like the bug,” said Anushree Chatterjee, an assistant professor in CHBE and the co-lead author of the study. “This is a novel strategy that plays against the infection’s normal strength and catalyzes the antibiotic instead.”

While other previous antibiotic treatments have proven too indiscriminate in their attack, the quantum dots have the advantage of being able to work selectively on an intracellular level. Salmonella, for example, can grow and reproduce inside host cells. The dots, however, are small enough to slip inside and help clear the infection from within.

“These super-resistant bugs already exist right now, especially in hospitals,” said Nagpal. “It’s just a matter of not contracting them. But they are one mutation away from becoming much more widespread infections.”

Overall, Chatterjee said, the most important advantage of the quantum dot technology is that it offers clinicians an adaptable multifaceted approach to fighting infections that are already straining the limits of current treatments.

“Disease works much faster than we do,” she said. “Medicine needs to evolve as well.”

Going forward, the researchers envision quantum dots as a kind of platform technology that can be scaled and modified to combat a wide range of infections and potentially expand to other therapeutic applications.