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.

WHO Issues Guidelines on Antibiotic Use to Fight Antibiotic Resistance

The WHO notes that the costs of losing antibiotic effectiveness will be literally worth tens of trillions of dollars.

To address the major and growing global threat that stems from rampant overuse and misuse of antibiotics in agriculture, the World Health Organization (WHO) this week issued its first-ever formal guidelines instructing farmers to stop using so many antimicrobials in healthy livestock.

“If no action is taken today, by 2050, almost all current antibiotics will be ineffective in preventing and treating human disease, and the costs of losing these drugs will exceed U.S. $100 trillion in terms of national productivity,” the U.N. agency predicts in a related policy brief (pdf).

David Wallinga, a senior health officer at the Natural Resources Defense Council (NRDC), said the guidelines “may be a game-changer in this fight,” because they call for “fairly significant changes to how many of the world’s biggest food-animal producers now operate, including the U.S.”—but “as important as these guidelines are, they are just that—guidelines. To help curb resistance, individual companies and/or countries actually have to take action on them.”

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The WHO guidelines reflect growing concerns about the amount of antibiotics used in agriculture, and what that means for both humans and animals in the long term.

As Kazuaki Miyagishima, director of the WHO’s Department of Food Safety and Zoonosesn, explains: “the volume of antibiotics used in animals is continuing to increase worldwide, driven by a growing demand for foods of animal origin,” and “scientific evidence demonstrates that overuse of antibiotics in animals can contribute to the emergence of antibiotic resistance.”

WHO Director-General Tedros Adhanom Ghebreyesus warns that “a lack of effective antibiotics is as serious a security threat as a sudden and deadly disease outbreak.”

“Driven by the need to mitigate the adverse human health consequences of use of medically important antimicrobials in food-producing animals,” the guidelines (pdf) include four recommendations:

  • An overall reduction in use of all classes of medically important antimicrobials in food-producing animals;
  • Complete restriction of use of these antimicrobials in food-producing animals for growth promotions;
  • Complete restriction of use for prevention of infectious diseases that have not yet been clinically diagnosed; and
  • Antimicrobials classified by the WHO as “highest priority critically important” for human medicine should not ever be used to treat food-producing animals, while antimicrobials classified as “critically important” should not be used to control the dissemination of an infection within a group of food-producing animals.

Since 2005, WHO has published a list of antimicrobials categorized as “important,” “highly important,” or “critically important” to human medicine, with the goal of preserving the effectiveness of available antibiotics. The latest revision (pdf) was published in April 2017.

The guidelines also feature two best practice statements. In the first, the WHO declares that “any new class of antimicrobials or new antimicrobial combination developed for use in humans will be considered critically important for human medicine unless otherwise categorized by WHO.”

The second statement advises that “medically important antimicrobials that are not currently used in food production should not be used in future production including food-producing animals or plants,” acknowledging that although the guidelines focus on livestock rather than plants, using antibiotics on plants also contributes to antimicrobial resistance that can be transferred to humans.

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The guidelines were released just ahead of U.S. Antibiotic Awareness Week—an annual effort by the Centers for Disease Control and Prevention (CDC) to raise awareness about antibiotic resistance—which begins November 13. The CDC found that as of 2013, more than 2 million Americans are infected with antibiotic-resistant bacteria each year, and about 23,000 of those people die because of the infection.

Antibiotic Resistant Gonorrhea Spreading Around the World

This gonorrhea development is disturbing and warrants a massive investment for a program against antibiotic resistance. As in, several hundred billion dollars more aimed at this problem today would be a useful start. I say that because the problem of antibiotic resistance should be prevented from becoming worse, as the costs to solve it a few decades from now will be higher and carry more consequences than solving it today will.

As drug-resistant gonorrhea rapidly spreads around the world, one team of researchers may have a strategy to combat it, according to a new study.

Gonorrhea is becoming a superbug, meaning the drugs typically used to treat it are no longer reliably effective. Should gonorrhea’s antibiotic resistance continue to increase, the results could be bleak, given that the sexually transmitted disease can cause long-term complications like infertility if left untreated.

In July, the World Health Organization (WHO) reported that around the globe, about 78 million people are infected with gonorrhea each year, and that 97% of 77 countries surveyed from 2009 to 2014 reported the presence of drug-resistant gonorrhea strains. Sixty-six percent of the countries reported the emergence of resistance to last resort drug treatments for the infection.

If a person gets a resistant strain of gonorrhea today, it doesn’t necessarily mean that they won’t ever clear the infection. “At the moment, all cases of gonorrhea are still treatable using some combination of available antibiotics,” says Dr. Xavier Didelot, senior lecturer in the department of infectious disease and epidemiology at Imperial College London. “But at the current rate at which resistance is developing, we could find ourselves facing a situation where no antibiotic works, which would mean a return to the pre-antibiotic era.”

To prevent that from happening, researchers are working to figure out new treatment strategies for gonorrhea. In a new study published Tuesday in the journal PLOS Medicine, Didelot and his colleagues report that relying more on an older drug for the disease may stop it from becoming more resistant to antibiotics.

To deal with gonorrhea infections, health experts in the United States currently recommend a combined therapy of the antibiotics ceftriaxone (and injection) azithromycin (taken orally). Dr. Bob Kirkcaldy, an epidemiologist at the U.S. Centers for Disease Control and Prevention’s (CDC) Division of STD Prevention, says that researchers have noticed that gonorrhea strains are becoming less responsive to both antibiotics. But he adds that if a person’s gonorrhea strain is resistant to one drug, it typically responds to the other. Kirkcaldy says it is still “unusual” for a gonorrhea strain in the U.S. to not respond at all to antibiotics.

“Currently recommended therapy is still highly effective,” says Kirkcaldy. “But given the history and what we’ve seen, that may not always be the case.”

Previously Unknown Antibiotic Resistance Genes Found

This discovery is beneficial, as it’s necessary to examine a difficult problem well to solve it effectively.

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have found several previously unknown genes that make bacteria resistant to last-resort antibiotics. The genes were found by searching large volumes of bacterial DNA and the results are published in the scientific journal Microbiome.

The increasing number of infections caused by antibiotic-resistant bacteria is a rapidly growing global problem. Disease-causing bacteria become resistant through mutations of their own DNA or by acquiring resistance genes from other, often harmless, bacteria.

By analysing large volumes of DNA data, the researchers found 76 new types of resistance genes. Several of these genes can provide bacteria with the ability to degrade carbapenems, our most powerful class of antibiotics used to treat multi-resistant bacteria.

“Our study shows that there are lots of unknown resistance genes. Knowledge about these genes makes it possible to more effectively find and hopefully tackle new forms of multi-resistant bacteria,” says Erik Kristiansson, Professor in biostatistics at Chalmers University of Technology and principal investigator of the study.

“The more we know about how bacteria can defend themselves against antibiotics, the better are our odds for developing effective, new drugs,” explains co-author Joakim Larsson, Professor in environmental pharmacology and Director of the Centre for Antibiotic Resistance Research at the University of Gothenburg.

The researchers identified the novel genes by analysing DNA sequences from bacteria collected from humans and various environments from all over the world.

“Resistance genes are often very rare, and a lot of DNA data needs to be examined before a new gene can be found,” Kristiansson says.

Identifying a resistance gene is also challenging if it has not previously been encountered. The research group solved this by developing new computational methods to find patterns in DNA that are associated with antibiotic resistance. By testing the genes they identified in the laboratory, they could then prove that their predictions were correct.

“Our methods are very efficient and can search for the specific patterns of novel resistance genes in large volumes of DNA sequence data,” says Fanny Berglund, a PhD student in the research group.

The next step for the research groups is to search for genes that provide resistance to other forms of antibiotics.

“The novel genes we discovered are only the tip of the iceberg. There are still many unidentified antibiotic resistance genes that could become major global health problems in the future,” Kristiansson says.

England’s Chief Medical Officer: Antibiotic Resistance Could Spell End of Modern Medicine

It’s worth posting this warning about antibiotic resistance again. The suggestions I have are to invest in a massive international research effort against antibiotic resistance, seek an end to factory farming, and to convince medical doctors to stop prescribing too many antibiotics. There would also be benefit in trying to prevent people from becoming ill in the first place too.

England’s chief medical officer has repeated her warning of a “post-antibiotic apocalypse” as she urged world leaders to address the growing threat of antibiotic resistance.

Prof Dame Sally Davies said that if antibiotics lose their effectiveness it would spell “the end of modern medicine”. Without the drugs used to fight infections, common medical interventions such as caesarean sections, cancer treatments and hip replacements would become incredibly risky and transplant medicine would be a thing of the past, she said.

“We really are facing – if we don’t take action now – a dreadful post-antibiotic apocalypse. I don’t want to say to my children that I didn’t do my best to protect them and their children,” Davies said.

Health experts have previously said resistance to antimicrobial drugs could cause a bigger threat to mankind than cancer. In recent years, the UK has led a drive to raise global awareness of the threat posed to modern medicine by antimicrobial resistance (AMR).

Each year about 700,000 people around the world die due to drug-resistant infections including tuberculosis, HIV and malaria. If no action is taken, it has been estimated that drug-resistant infections will kill 10 million people a year by 2050.

The UK government and the Wellcome Trust, along with others, have organised a call to action meeting for health officials from around the world. At the meeting in Berlin, the government will announce a new project that will map the spread of death and disease caused by drug-resistant superbugs.

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“It does not really have a ‘face’ because most people who die of drug-resistant infections, their families just think they died of an uncontrolled infection. It will only get worse unless we take strong action everywhere across the globe. We need some real work on the ground to make a difference or we risk the end of modern medicine.”

She added: “Not to be able to effectively treat infections means that caesarean sections, hip replacements, modern surgery, is risky. Modern cancer treatment is risky and transplant medicine becomes a thing of the past.”

Davies said that if the global community did not act then the progress that had been made in Britain may be undermined.

She estimated that about one in three or one in four prescriptions in UK primary care were probably not needed. “But other countries use vastly more antibiotics in the community and they need to start doing as we are, which is reducing usage,” she said. “Our latest data shows that we have reduced human consumption by 4.3% in 2014-15 from the year before.”

Doctors “Sound Alarm Over Drug Resistance”

Antibiotic resistance is among the most serious problems in modern times. There needs to be a massive research effort where the science is kept open so that it advances most efficiently. Humans are risking another disaster similar to the 1918 influenza pandemic by failing to do so.

In only the several decades, the antibiotic problem has gotten a lot worse. I hope that a lot of these problems will be solved in the next few decades, as I think they are going to be key building blocks for a brighter future.

Scientists attending a recent meeting of the American Society for Microbiology reported they had uncovered a highly disturbing trend. They revealed that bacteria containing a gene known as mcr-1 – which confers resistance to the antibiotic colistin – had spread round the world at an alarming rate since its original discovery 18 months earlier. In one area of China, it was found that 25% of hospital patients now carried the gene.

Colistin is known as the “antibiotic of last resort”. In many parts of the world doctors have turned to its use because patients were no longer responding to any other antimicrobial agent. Now resistance to its use is spreading across the globe.

In the words of England’s chief medical officer, Sally Davies: “The world is facing an antibiotic apocalypse.” Unless action is taken to halt the practices that have allowed antimicrobial resistance to spread and ways are found to develop new types of antibiotics, we could return to the days when routine operations, simple wounds or straightforward infections could pose real threats to life, she warns.

That terrifying prospect will be the focus of a major international conference to be held in Berlin this week. Organised by the UK government, the Wellcome Trust, the UN and several other national governments, the meeting will be attended by scientists, health officers, pharmaceutical chiefs and politicians. Its task is to try to accelerate measures to halt the spread of drug resistance, which now threatens to remove many of the major weapons currently deployed by doctors in their war against disease.

The arithmetic is stark and disturbing, as the conference organisers make clear. At present about 700,000 people a year die from drug-resistant infections. However, this global figure is growing relentlessly and could reach 10 million a year by 2050.

The danger, say scientists, is one of the greatest that humanity has faced in recent times. In a drug-resistant world, many aspects of modern medicine would simply become impossible. An example is provided by transplant surgery. During operations, patients’ immune systems have to be suppressed to stop them rejecting a new organ, leaving them prey to infections. So doctors use immunosuppressant cancer drugs. In future, however, these may no longer be effective.

Or take the example of more standard operations, such as abdominal surgery or the removal of a patient’s appendix. Without antibiotics to protect them during these procedures, people will die of peritonitis or other infections. The world will face the same risks as it did before Alexander Fleming discovered penicillin in 1928.

“Routine surgery, joint replacements, caesarean sections, and chemotherapy also depend on antibiotics, and will also be at risk,” says Jonathan Pearce, head of infections and immunity at the UK Medical Research Council. “Common infections could kill again.”

As to the causes of this growing threat, scientists point to the widespread misuse and overuse of antibiotics and other drugs and to the failure of pharmaceutical companies to investigate and develop new sources of general medicines for the future. Western doctors are over-prescribing antibiotics to patients who expect to be given a drug for whatever complaint they have. In many countries, both land and fish farmers use antibiotics as growth promoters and indiscriminately pour them on to their livestock. In the latter case the end result is antibiotics leaching into streams and rivers with alarming results, particularly in Asia.

“In the Ganges during pilgrimage season, there are levels of antibiotics in the river that we try to achieve in the bloodstream of patients,” says Davies. “That is very, very disturbing.”

The creation of these soups of antibiotic-laden waters and banks of drug-soaked soils is ideal for the development of “superbugs”. Rare strains that are resistant to antibiotics start to thrive in farm animals that are raised in these artificial environments and emerge as highly potent infectious agents that then spread across the planet with startling speed. Examples of these include tuberculosis, which was once easily treated but which, in its modern multi-drug-resistant form, known as MDR-TB, now claims the lives of 190,000 people a year.

Another even more revealing example is provided by colistin. “Colistin was developed in the 50s,” says Matthew Avison, reader in molecular biology at Bristol University. “However, its toxic side-effects made it unpopular with doctors. So it was taken up by vets and used in animals. But as resistance – in humans – to other antibiotics has spread, doctors have returned to colistin on the grounds that it was better than nothing.”

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Then there is the issue of travel, one of the biggest problems we face over the spread of antimicrobial resistance, according to Davies, who has spearheaded Britain’s part in the battle to fight its spread around the world.

“One Swedish study followed a group of young backpackers who went off on holiday to different parts of the world. None had resistant bacteria in their guts when they left. When they returned a quarter of them had picked up resistant bugs. That shows the pervasive nature of the problem we face,” she said.

Tourism, personal hygiene, farming, medical practice – all are affected by the issue of antibiotic resistance, and it will be the task of the conference to highlight the most effective and speedy solutions to tackle the crisis.

“In the end, the problem posed to the planet by antimicrobial resistance is not that difficult,” says O’Neill. “All that is required is to get people to behave differently. How you achieve that is not so clear, of course.”

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.