Tag: antibiotic resistance

Categories : AntibioticsTags :

Breathing New Life into Old Antibiotics

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Source: Pixabay CC0

Scientists may have hit upon a way to make frontline antibiotics once again effective against the deadly bacteria that cause pneumonia.

The international team originally developed this as a potential treatment for disorders such as Alzheimer’s, Parkinson’s and Huntington’s diseases to break bacterial resistance to commonly used frontline antibiotics.

Led by University of Melbourne Professor Christopher McDevitt, this discovery may see the comeback of readily available and cheap antibiotics, such as penicillin and ampicillin, as effective weapons in the fight against the rapidly rising threat of antibiotic resistance.

In a paper published in Cell Reports, Prof McDevitt and colleagues described how they discovered a way to break bacterial drug resistance and then developed a therapeutic approach to rescue the use of the antibiotic ampicillin to treat drug-resistant bacterial pneumonia caused by Streptococcus pneumoniae in a mouse model of infection.

The World Health Organization (WHO) last year named antibiotic resistance as one of the greatest threats to global health, food security, and development. Rising numbers of bacterial infections such as pneumonia, tuberculosis, gonorrhoea, and salmonellosis are becoming harder to treat as the antibiotics lose effectiveness against them.

Prof McDevitt’s prior work on bacterial antibiotic resistance using zinc ionophores led to collaborations with University of Queensland’s Professor Mark Walker and Griffith University’s Professor Mark von Itzstein from the Institute for Glycomics.

“We knew that some ionophores, such as PBT2, had been through clinical trials and shown to be safe for use in humans,” Prof von Itzstein said.

Prof Walker said that “as a group, we realised that if we could repurpose these safe molecules to break bacterial resistance and restore antibiotic efficacy, this would be a pathway to a therapeutic treatment. What we had to do was show whether PBT2 broke bacterial resistance to antibiotic treatment without leading to even greater drug resistance.”

“We focused on bacterial pneumonia and the most commonly used antibiotics. We thought that if we could rescue frontline antibiotics and restore their use for treating common infections, this would solve a global problem,” Prof McDevitt added.

An important component was the research from Prof McDevitt’s group that led to making the treatment effective.

“We knew from earlier research that the immune system uses zinc as an innate antimicrobial to fight off infection. So, we developed our therapeutic approach with PBT2 to use the body’s antimicrobial zinc to break antibiotic resistance in the invading bacteria,” he said.

“This rendered the drug-resistant bacteria susceptible to the antibiotic ampicillin, restoring the effectiveness of the antibiotic treatment in the infected animals.”

Collecting the data required for a clinical trial of PBT2 in combination with antibiotics is the next step, said Prof McDevitt.

“We also want to find other antibiotic-PBT2 combinations that have therapeutic potential for treatment of other bacterial infections,” he said.

“Our work shows that this simple combination therapy is safe, but the combinations require testing in clinical trials. What we need now is to move forward with further testing and pharmacology.”

Source: University of Melbourne

Categories : AntibioticsTags :

Hedgehog Discovery Shows MRSA Evolved Before the Advent of Antibiotics

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Photo by Alexas_Fotos on Unsplash

A surprising discovery in hedgehogs showed that a variant of the MRSA superbug appeared in nature well before antibiotics use in humans and livestock, which has traditionally been blamed for its emergence.

Staphylococcus aureus first developed resistance to the antibiotic methicillin around 200 years ago, according to a large international study which has traced the genetic history of the bacteria.

The finding comes from research showing that up to 60% of hedgehogs in Denmark and Sweden carry a type of MRSA called mecC-MRSA. The new study also found high levels of MRSA in swabs taken from hedgehogs across their range in Europe and New Zealand. Their findings were published in the journal Nature.

The researchers believe that antibiotic resistance evolved in S. aureus as an adaptation to having to exist on hedgehog skin next to the fungus Trichophyton erinacei, which produces its own antibiotics. The discovery of this centuries-old antibiotic resistance predates antibiotic use in medical and agricultural settings.

“Using sequencing technology we have traced the genes that give mecC-MRSA its antibiotic resistance all the way back to their first appearance, and found they were around in the nineteenth century,” said Dr Ewan Harrison, a senior author of the study.

He added: “Our study suggests that it wasn’t the use of penicillin that drove the initial emergence of MRSA, it was a natural biological process. We think MRSA evolved in a battle for survival on the skin of hedgehogs, and subsequently spread to livestock and humans through direct contact.”

Antibiotic resistance in human pathogens was previously thought to be a modern phenomenon, driven by the clinical use of antibiotics. Antibiotic misuse is now accelerating the process, with antibiotic resistance rising dangerously worldwide.

Since nearly all antibiotics used today arose in nature, the researchers say it is likely that resistance to them already exists in nature too. Overuse of any antibiotic in humans or livestock will favour resistant strains of the bacteria, causing it to lose effectiveness over time.

“This study is a stark warning that when we use antibiotics, we have to use them with care. There’s a very big wildlife ‘reservoir’ where antibiotic-resistant bacteria can survive – and from there it’s a short step for them to be picked up by livestock, and then to infect humans,” said Professor Mark Holmes, a senior author of the report.

In 2011, mecC -MRSA was identified in human and dairy cow populations, which was assumed to have arisen due to the large number of antibiotics cows are routinely given.

MRSA was first identified in patients in 1960, and around 1 in 200 of all MRSA infections are caused by mecC-MRSA. Due to its resistance to antibiotics, MRSA is much harder to treat than other bacterial infections. The World Health Organization now considers MRSA one of the world’s greatest threats to human health.

Human infections are rare with mecC-MRSA however, even though it has been present in hedgehogs for more than 200 years.

Source: University of Cambridge

Categories : Antibiotics Diseases, Syndromes and ConditionsTags :

Signs of Antibiotic ‘Pre-resistance’ Identified for the First Time

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Drug-resistant, Mycobacterium tuberculosis bacteria, the pathogen responsible for causing the disease tuberculosis (TB). A 3D computer-generated image. Credit: CDC

In a first of its kind study, researchers have spotted signs of antibiotic ‘pre-resistance’ in bacteria for the first time, indicating that they have the potential to develop drug resistance in the future.

The findings, published in Nature Communications, will allow doctors in the future to select the best treatments for bacterial infections.

Mycobacterium tuberculosis (TB) was the second leading infectious cause of death after COVID in 2020, killing 1.5m people. It can be cured if treated with the right antibiotics, but treatment is lengthy and many people most at risk lack access to adequate healthcare. Drug-resistant TB can develop when people do not finish their full course of treatment, or when drugs are not available or are of poor quality.

Multi-drug resistant TB represents a huge, unsustainable burden and totally drug resistant strains have been detected in a handful of countries. As health systems struggle to cope with the pandemic, progress on TB treatment globally has slowed.

To better understand TB for developing new drugs, this study has identified for the first time how to pre-empt drug resistance mutations before they have occurred. Dubbed ‘pre-resistance’ when a pathogen has a greater inherent risk of developing resistance to drugs in the future.

By analysing thousands of bacterial genomes, the study has potential application to other infectious diseases and paves the way towards personalised pathogen ‘genomic therapy’ – which chooses drugs according to the pathogen, preventing drug resistance.

The culmination of 17 years’ work, the study built up a TB bacterial ‘family tree’  from 3135 different tuberculosis samples. Computational analysis identified the ancestral genetic code of bacteria that then went on to develop drug resistance. The team identified the key changes associated with the development of resistance by looking through the ‘branches’ of the family tree to see which had the most potential for developing drug resistance.

Variations in the TB genome predicted that a particular branch would likely become drug resistant, and then validated their findings in an independent global TB data set.

Dr Grandjean, senior author of the study, said: “We’re running out of options in antibiotics and the options we have are often toxic – we have to get smarter at using what we have to prevent drug resistance.

“This is the first example of showing that we can get ahead of drug resistance. That will allow us in the future to use the pathogen genome to select the best treatments.”

Source: EurekAlert!

Categories : Medical Research & TechnologyTags :

Understanding Mechanisms of Antibiotic Resistance

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Source: NCI

If nothing is done, the problem of multidrug-resistant bacterial infections could be catastrophic by 2050, killing nearly 10 million people each year, according to experts’ predictions.

One person seeking solutions is Joseph Boll, assistant professor of biology at The University of Texas at Arlington, to identify and inhibit the defense mechanisms of Acinetobacter baumannii, a common pathogen in hospitals and clinical settings.

A. baumannii can cause infections in the blood, urinary tract and lungs, or in wounds in other parts of the body. Antibiotics are usually used to treat the infections, but many strains are resistant, including drugs of last resort, carbapenems.

“In previous research, we discovered that when A. baumannii experiences stress, such as antibiotic treatment, it modifies its cell envelope to tolerate the antibiotic for extended periods of time,” Prof Boll said. “Specific modifications allow the bacteria to survive long enough to acquire true antibiotic resistance, which can lead to antibiotic treatment failure. This can happen within 24 hours of antibiotic exposure.”

His team expects to identify what adaptations in the cell envelope allow the pathogen to survive in the presence of antibiotics and how survival contributes to the acquisition of true resistance.

In a recent study published in mBio, the team demonstrated that two LD-transpeptidase enzymes remodel A. baumannii’s cell envelope to promote its survival when under stress, such as the kind experienced during antibiotic treatment.

With this breakthrough, Hannah Bovermann, a senior double-major in biology and microbiology, is dissecting the genes that encode the bacteria’s LD-transpeptidases to learn what stress conditions induce their activation. She isolates the LD-transpeptidase promoters, the part of the DNA that controls when other parts of DNA are used, and glues it to a different gene whose function is to turn the bacterial cell blue. When the cell is in an environment where it wants to modify its cell envelope to protect itself, it turns blue, letting her observe the timing of the change.

To provoke this reaction, she administers antibiotics, experiments with various temperature changes, exposes the cell to pH gradients and subjects the cell to nutrient deprivations.

“Each response brings us closer to an understanding of how cell envelope modifications keep the bacterial cell intact in stress,” Bovermann said.

The researchers hope to find new targets on the cell surface for antibiotics to attack, strengthening existing medications’ potency against A. baumannii infections.

Clinicians have been pushed into using combinatorial therapies, where multiple drugs are employed to treat bacterial infections, but even those methods are becoming increasingly ineffective, Prof Boll said.

“It has become a game. Researchers discover a new antimicrobial, then bacteria become resistant to it. We are running out of options,” Prof Boll said. “Bacterial resistance is quickly outpacing new antibiotic development.”

Source: EurekAlert!

Categories : Antibiotics New Compounds and TreatmentsTags :

New Antibacterial Molecules Identified

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Source: National Cancer Institute on Unsplash

Researchers have identified a new group of molecules with an antibacterial effect against many antibiotic-resistant bacteria. Since the properties of the molecules can easily be altered chemically, the hope is to develop new, effective antibiotics with few side effects. The study appears in PNAS.

Increasing antibiotic resistance is a great concern as few new antibiotics have been developed in the past 50 years.

Most antibiotics work by inhibiting the bacteria’s ability to form a protective cell wall, causing the bacteria to crack (cell lysis). Besides the well-known penicillin, which inhibits enzymes building up the wall, newer antibiotics such as daptomycin or the recently discovered teixobactin bind to a special molecule, lipid II. All bacteria need lipid II as a building block for the cell wall. Antibiotics that bind to Lipid II are usually very large and complex molecules and therefore more difficult to improve with chemical methods. These molecules are in addition mostly inactive against a group of problematic bacteria, which are surrounded by an additional layer, the outer membrane, that hinders penetration of these antibacterials.

“Lipid II is a very attractive target for new antibiotics. We have identified the first small antibacterial compounds that work by binding to this lipid molecule, and in our study, we found no resistant bacterial mutants, which is very promising,” says Birgitta Henriques Normark, professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and one of the article’s three corresponding authors.

For this study, published in PNAS, researchers tested a large number of chemical compounds for their ability to lyse pneumococci – the most common cause of community-acquired pneumonia. After a careful follow-up of active compounds from this screening, the researchers found that a group of molecules called THCz inhibits the formation of the cell wall of the bacterium by binding to lipid II. The molecules could also prevent the formation of the sugar capsule that pneumococci need to escape the immune system and to cause disease.

Small molecules offer several benefits, noted Fredrik Almqvist, professor at Umeå University and one of the corresponding authors: “The advantage of small molecules like these is that they are more easy to change chemically. We hope to be able to change THCz so that the antibacterial effect increases and any negative effects on human cells decrease.”

Laboratory work with THCz showed it has an antibacterial effect against many antibiotic-resistant bacteria, such as methicillin-resistant staphylococci (MRSA), vancomycin-resistant enterococci (VRE), and penicillin-resistant pneumococci (PNSP). An antibacterial effect was also found against gonococci, which causes gonorrhoea, and mycobacteria, bacteria that can cause severe diseases such as tuberculosis in humans. None of the bacteria managed to develop resistance to THCz in a laboratory environment.

“We will now also initiate attempts to change the THCz molecule, allowing it to penetrate the outer cell membrane found in some, especially intractable, multi-resistant bacteria,” says Tanja Schneider, professor at the Institute of Pharmaceutical Microbiology at the University of Bonn and one of the corresponding authors.

Source: Karolinska Institutet

Categories : Antibiotics Diseases, Syndromes and ConditionsTags :

Insects Carry a Range of Antimicrobial-resistant Bacteria

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A study published in Nature Microbiology has for the first time provided compelling evidence of connections between antimicrobial-resistant bacteria causing surgical-site infections and insects and other arthropods. Among these bacteria are those with resistance to drug-of-last-resort. 

Antimicrobial resistance (AMR) could render many of the current mainstay and last-resort antibiotics useless, resulting in many more deaths from previously treatable infections. A UN report estimated in 2019 that AMR could lead to ten million deaths per year, and cost the world $100 trillion, by 2050.

“Similar to our experience over the last eighteen months with the pandemic, a problem currently seen from afar will quickly come into focus much closer to home” said Professor Tim Walsh at Oxford University

The report found that:

  • About 20% of the flies, cockroaches, spiders, moths, and ants were carrying carbapenem resistance.
  • Of these, 70-80% were carrying extended spectrum cephalosporin resistance, that is, enzymes that confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam.
  • Currently there are about 18 million flies to every human, but conservative global warming projections estimate insect and fly population will double if temperatures increase by 1.5 degrees.
  • By 2080 there could be around 50 000 trillion flies carrying carbapenem resistance and spreading AMR across the planet.

“Similar to our experience over the last eighteen months with the pandemic, a problem currently seen from afar will quickly come into focus much closer to home,” said Prof Walsh. “The clinical burden of AMR is most felt in low-middle income countries, but the increase in global temperatures, due to climate change, will result in a significant increase in flies and many other insects and a subsequent increase in the global velocity of antibiotic resistance.” Prof. Tim Walsh, Oxford University.

AMR is a pervasive issue, stretching from hospitals to farming and human waste processing. Resistance can spread within hospitals, communities, farms, and wastewater systems, and domestic animals can share AMR microorganisms with humans.

One tactic is to repurpose previously developed drugs that did not work for humans and use these for animals, buying time for us to develop new drugs.

Another is to rethink hospital prevention and infection control measures, especially in lower- and middle-income countries. Further research into how arthropods disseminate AMR and improving healthcare infrastructure to reduce the spread of AMR by arthropods.

“Most antibiotics currently used on animals are also the same that are used in humans, creating a pool where bacteria can evolve to evade drugs and then reinfect humans,” said Prof Tim Walsh of Oxford University.

“There is no silver bullet when it comes to tackling the worldwide threat of AMR,” he added. “The Ineos Oxford Institute for AMR Research is committed to finding non-human antibiotic therapies and feeds for animals, addressing the increase in AMR in human infections and raising awareness of this hidden threat to human health. But this is a global medical crisis that ultimately will only be resolved with a global response.”

Source: Oxford University

Categories : Antibiotics Medical Research & TechnologyTags :

Human Breast Milk Could Yield Antibiotic Secrets

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Researchers believe that antibacterial properties of sugars in human breast milk could be harnessed for new antimicrobial therapies.

Group B Streptococcus (GBS) bacteria are a common cause of blood infections, meningitis and stillbirth in newborns, and are becoming resistant to antibiotics. Researchers have now discovered that human milk oligosaccharides (HMOs), short strings of sugar molecules abundant in breast milk, can help prevent GBS infections in human cells and tissues and in mice. This might yield new antibiotic treatments, the researchers believe. 

“Our lab has previously shown that mixtures of HMOs isolated from the milk of several different donor mothers have antimicrobial and antibiofilm activity against GBS,” says Rebecca Moore, who is presenting the work at a meeting of the American Chemical Society (ACS). “We wanted to jump from these in vitro studies to see whether HMOs could prevent infections in cells and tissues from a pregnant woman, and in pregnant mice.” Moore is a graduate student in the labs of Steven Townsend, PhD, at Vanderbilt University and Jennifer Gaddy, PhD, at Vanderbilt University Medical Center.

According to the US Centers for Disease Control and Prevention, about 2000 babies in the U.S. get GBS each year, with 4-6% of them dying from it. The bacteria are often transferred from mother to baby during labour and delivery. An expectant mother who tests positive for GBS is usually given intravenous antibiotics during labor to help prevent early-onset infections, which occur during the first week of life. Notably, late-onset infections (which happen from one week to three months after birth) are more common in formula-fed than breastfed infants, suggesting breast milk has factors which could help protect against GBS. If so, the sugars could be a replacement for current antibiotics which are steadily becoming less effective.

The researchers studied the effects of combined HMOs from several mothers on GBS infection of placental macrophages and of the gestational membrane. “We found that HMOs were able to completely inhibit bacterial growth in both the macrophages and the membranes, so we very quickly turned to looking at a mouse model,” Moore says. They examined whether HMOs could prevent a GBS infection from spreading through the reproductive tract of pregnant mice. “In five different parts of the reproductive tract, we saw significantly decreased GBS infection with HMO treatment,” Moore notes.

To determine which HMOs and other oligosaccharides have these antimicrobial effects and why, the researchers made an artificial two-species microbiome with GBS and the beneficial Streptococcus salivarius species growing in a tissue culture plate, separated by a semi-permeable membrane. Then, the researchers added oligosaccharides that are commonly added to infant formula, called galacto-oligosaccharides (GOS), which are derived from plants. In the absence of the sugar, GBS suppressed the growth of the “good” bacteria, but GOS helped this beneficial species grow. “We concluded that GBS is producing lactic acid that inhibits growth, and then when we add the oligosaccharide, the beneficial species can use it as a food source to overcome this suppression,” Moore explained.
The first HMOs tested did not have this effect, but Townsend says it’s likely that one or more of the over 200 unique sugars in human milk will show activity in the artificial microbiome assay. There are likely two reasons why HMOs can treat and prevent GBS infection: they prevent pathogens from sticking to tissue surfaces and forming a biofilm, and they could also act as a prebiotic by promoting good bacteria growth.

“HMOs have been around as long as humans have, and bacteria have not figured them out. Presumably, that’s because there are so many in milk, and they’re constantly changing during a baby’s development,” Townsend said. “But if we could learn more about how they work, it’s possible that we could treat different types of infections with mixtures of HMOs, and maybe one day this could be a substitute for antibiotics in adults, as well as babies.”

Source: American Chemical Society

Categories : Diseases, Syndromes and ConditionsTags :

Human Transmission in Antibiotic-resistant Plague Outbreak

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Scanning electron micrograph of Yersinia pestis, which causes bubonic plague, on proventricular spines of a Xenopsylla cheopis flea.
 
Credit: National Institute of Allergy and Infectious Diseases/NIH


Analysing a recent outbreak of plague in Madagascar, a team of researchers uncovered evidence of human transmission of antimicrobial-resistant plague.

While COVID dominates the global awareness of infectious diseases, others are still out there, such as Yersinia pestis, which causes plague. Even though plague has been largely eradicated in the developed world, hundreds of people globally contract it each year.

When a human is infected with bubonic plague from a flea bite and it goes untreated, the infection can progress, spread to the lungs and resulting in pneumonic plague. Pneumonic plague is usually lethal if not treated quickly, and infected patients can transmit the disease to others via respiratory droplets. A team of scientists from Northern Arizona University’s Pathogen and Microbiome Institute, led by professor Dave Wagner, recently published their findings from a remarkable study involving antimicrobial resistant (AMR) plague.

Plague is considered to be a reemerging and neglected disease, particularly in the East African island country of Madagascar, which reports the majority of annual global cases. There is no vaccine for it, so preventing mortality from plague requires rapid diagnosis followed by antibiotic treatment. In Madagascar, the antibiotic streptomycin is usually the first-line treatment for plague. The researchers isolated a streptomycin-resistant AMR strain of Y. pestis from a pneumonic plague outbreak that occurred there in 2013, involving 22 cases, including three fatalities. The study was recently published in Clinical Infectious Diseases.

“By characterising the outbreak using epidemiology, clinical diagnostics and DNA-fingerprinting approaches,” Prof Wagner said, “we determined—for the first time—that AMR strains of Y. pestis can be transmitted person-to-person. The AMR strain from this outbreak is resistant to streptomycin due to a spontaneous point mutation, but is still susceptible to many other antibiotics, including co-trimoxazole. Luckily, the 19 cases that were treated all received co-trimoxazole in addition to streptomycin, and all of them survived.

“The point mutation, which also is the source of streptomycin resistance in other bacterial species, has occurred independently in Y. pestis at least three times and appears to have no negative effect on the AMR strain, suggesting that it could potentially persist in nature via the natural rodent-flea transmission cycle. However, AMR Y. pestis strains are exceedingly rare and the mutation has not been observed again in Madagascar since this outbreak.”

Source: North Arizona University

Categories : Antibiotics CancerTags :

Old Antibiotics as New Weapons against Melanoma

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Researchers may have hit upon a new weapon in the fight against melanoma: antibiotics that target a vulnerability in the ‘power plants’ of cancer cells when they try to survive cancer therapy.

“As the cancer evolves, some melanoma cells may escape the treatment and stop proliferating to ‘hide’ from the immune system. These are the cells that have the potential to form a new tumor mass at a later stage,” explains cancer researcher and RNA biologist Eleonora Leucci at KU Leuven, Belgium. “In order to survive the cancer treatment however, those inactive cells need to keep their ‘power plants’—the mitochondria—switched on at all times.” As mitochondria derive from bacteria that, over time, started living inside cells, they are very vulnerable to a specific class of antibiotics. This is what gave us the idea to use these antibiotics as anti-melanoma agents.”

The researchers implanted patient-derived tumors into mice, which were then treated with antibiotics, either as alone or in combined with existing anti-melanoma therapies. Leucci observed: “The antibiotics quickly killed many cancer cells and could thus be used to buy the precious time needed for immunotherapy to kick in. In tumors that were no longer responding to targeted therapies, the antibiotics extended the lifespan of—and in some cases even cured—the mice.”

The researchers made use of nearly antibiotics rendered nearly obsolete because of antibiotic resistance. However, this does not affect the efficacy of the treatment in this study, Leucci explained. “The cancer cells show high sensitivity to these antibiotics, so we can now look to repurpose them to treat cancer instead of bacterial infections.”

However, patients with melanoma should not try to experiment, warned Leucci. “Our findings are based on research in mice, so we don’t know how effective this treatment is in human beings. Our study mentions only one human case where a melanoma patient received antibiotics to treat a bacterial infection, and this re-sensitized a resistant melanoma lesion to standard therapy. This result is cause for optimism, but we need more research and clinical studies to examine the use of antibiotics to treat cancer patients. Together with oncologist Oliver Bechter (KU Leuven/UZ Leuven), who is a co-author of this study, we are currently exploring our options.”

Source: KU Leuven

Journal information: Roberto Vendramin et al, Activation of the integrated stress response confers vulnerability to mitoribosome-targeting antibiotics in melanoma, Journal of Experimental Medicine (2021). DOI: 10.1084/jem.20210571

Categories : Antibiotics Diseases, Syndromes and ConditionsTags :

Untreated Sewage is a Driver of Antibiotic Resistance

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Photo by Jordan Opel on Unsplash
Photo by Jordan Opel on Unsplash

Contamination of urban lakes, rivers and surface water by human waste is creating pools of ‘superbugs’ in Low- and Middle-Income Countries (LMIC), according to new research. However, improving access to clean water, sanitation and sewerage infrastructure could help to improve public health.

For the study, researchers studied bodies of water in urban and rural sites in three areas of Bangladesh: Mymensingh, Shariatpur and Dhaka. In comparison to rural settings, they detected more antibiotic resistant faecal coliforms in urban surface water , consistent with reports of such bacteria in rivers across Asia. Their findings were published in mSystems.

Lead author Willem van Schaik, Professor of Microbiology and Infection at the University of Birmingham, commented: “The rivers and lakes of Dhaka are surrounded by highly-populated slums in which human waste is directly released into the water. The presence of human gut bacteria links to high levels of antibiotic resistance genes, suggesting that such contamination is driving the presence of these ‘superbugs’ in surface water.

“Interventions aimed at improving access to clean water, sanitation and sewerage infrastructure may thus be important to reduce the risk of antimicrobial resistance spreading in Bangladesh and other LMICs. While levels of antibiotic resistance genes are considerably lower in rural than in urban settings, we found that antibiotics are commonly used in fish farming and further policies need to be developed to reduce their use.”

Infections from antibiotic-resistant bacteria are on the rise globally, but the clinical issues posed by these bacteria are particularly alarming in LMICs, with significant morbidity and mortality. As in other LMICs, multidrug-resistant E. coli has a relatively high prevalence in healthy humans in Bangladesh.

With a population of around 16 million people, Dhaka’s population density ranks among the highest of any megacity, but less than 20% of its households have a sewerage connection.

Urban surface waters in Bangladesh are particularly rich in antibiotic resistance genes, the researchers discovered, with a higher number of them associated with plasmids — vehicles of genetic exchange among bacteria — indicating that they are more likely to spread through the population.

Antibiotic-resistant bacteria that colonise the human gut can be passed into rivers, lakes and coastal areas through the release of untreated wastewater, the overflow of pit latrines during monsoon season or by practices such as open defecation.

Such contaminated environments are often used for bathing, for the washing of clothes and food utensils, thereby risking human gut colonisation by antibiotic-resistant bacteria.

The researchers from the University of Birmingham and the International Centre for Diarrhoeal Disease Research, Bangladesh called for further research to quantify the drivers of antibiotic resistance in surface waters in Bangladesh.

Source: University of Birmingham

Journal information: McInnes, R.S., et al. (2021) Metagenome-Wide Analysis of Rural and Urban Surface Waters and Sediments in Bangladesh Identifies Human Waste as a Driver of Antibiotic Resistance. mSystems. doi.org/10.1128/mSystems.00137-21.