Tag: antibiotic resistance

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Disarming a Common Pathogenic Bacterium

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Pseudomonas aeruginosa bacteria. Source: Public Health Imagery Library

Scientists have discovered a gene regulator in a common pathogenic bacterium that can be exploited to drastically reduce its virulence.

Pseudomonas aeruginosa is a gram-negative, aerobic, opportunistic, pathogenic bacterium found in a variety of ecological niches, such as plant roots, stagnant water or even plumbing. Naturally extremely versatile, it can cause acute and chronic infections that are potentially fatal for immunocompromised hosts. P. aeruginosa poses a serious threat in clinical settings, where it can colonise respirators and catheters. Additionally, its adaptability and resistance to many antibiotics make P. aeruginosa infections steadily more difficult to treat. Therefore new antibacterials are urgently needed. 

Scientists from the University of Geneva (UNIGE) in Switzerland have identified a previously unknown regulator of gene expression in this bacterium, without which the infectious power of P. aeruginosa is diminished. This discovery may unlock new developmental pathways to treat this bacteria.

RNA helicases perform essential regulatory functions by binding and unwinding various RNA molecules to perform their functions. RNA helicases are present in the genomes of almost all known living organisms, including bacteria, yeast, plants, and humans; however, they have acquired specific properties depending on the organism in which they are found. “Pseudomonas aeruginosa has an RNA helicase whose function was unknown, but which was found in other pathogens”, explained Martina Valentini,  a researcher leading this research in the Department of Microbiology and Molecular Medicine at UNIGE Faculty of Medicine. “We wanted to understand what its role was, in particular in relation to the pathogenesis of the bacteria and their environmental adaptation.”

A severely reduced virulence

To accomplish this, the researchers took a combined biochemical and molecular genetic approach. “In the absence of this RNA helicase, P. aeruginosa multiplies normally in vitro, both in a liquid medium and on a semi-solid medium at 37°C”, reported Stéphane Hausmann, a researcher associate in the Department of Microbiology and Molecular Medicine at UNIGE Faculty of Medicine and first author of this study. “To determine whether the infection capacity of the bacteria was affected, we had to observe it in vivo in a living organism.”

The scientists then continued their research using Galleria mellonella larvae, a model insect for studying host-pathogen interactions.These larvae can live at temperatures between 5°C and 45°C, which makes it possible to study bacterial growth at different temperatures, including that of the human body. Three groups of larvae were observed, including a control group injected with saline. In the presence of a normal strain of P. aeruginosa, less than 20% survived at 20 hours after infection. In contrast, when P. aeruginosa lacked the RNA helicase gene, over 90% of the larvae remained alive. “The modified bacteria became almost harmless, while remaining very much alive,” says Stéphane Hausmann.

Inhibiting instead of killing

The findings demonstrated that the regulator affects production of several virulence factors in the bacteria. “In fact, this protein controls the degradation of numerous messenger RNAs coding for virulence factors”, summarised Martina Valentini. “From an antimicrobial drug strategy point of view, switching off the pathogen’s virulence factors rather than trying to eliminate the pathogen completely, means allowing the host immune system to naturally neutralise the bacterium and potentially reduces the risk for the development of resistance. Indeed, if we try to kill the bacteria at all costs, the bacteria will adapt to survive, which favours the appearance of resistant strains.”

The Geneva team is continuing its investigations by screening drug molecules to see if any of them can selectively block this protein, and also performing a detailed study in detail on the inhibition mechanisms on which could be based the development of an effective therapeutic strategy.

Source: University of Geneva

Journal reference: Hausmann, S., et al. (2021) The DEAD-box RNA helicase RhlE2 is a global regulator of Pseudomonas aeruginosa lifestyle and pathogenesis. Nucleic Acid Research. doi.org/10.1093/nar/gkab503.

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Holding off on Antibiotics is Safe and Effective for Patients

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According to an analysis published in BMJ Today, delayed antibiotic prescribing is a safe and effective strategy for most patients with respiratory tract infections.

Delayed antibiotic prescribing—also known as ‘just in case prescribing’—is when patients agree to see whether symptoms settle before collecting a prescription, in order to help reduce antibiotic use.

Delayed prescribing was shown to be associated with a similar duration of symptoms as no antibiotic prescribing and is not likely to lead to poorer symptom control than immediate antibiotic prescribing. In children with immediate antibiotics a slight benefit was seen but this was not judged important enough to justify immediate antibiotic prescribing.

Respiratory tract infections affect the sinuses, throat, airways or lungs and include conditions such as the common cold, sore throat, cough and ear infection. While most improve without treatment, antibiotics are still widely being prescribed for these conditions.

It has been suggested in various clinical trials that delayed antibiotic prescribing for respiratory tract infections is probably safe and effective for most patients, but they were unable to examine different groups of patients or complications.

To address this, an international research team set out to assess the effect of delayed antibiotic prescribing on symptoms for patients with respiratory tract infections in the community.

They used individual patient data on a total of 55 682 patients from nine randomised controlled trials and four observational studies to compare average symptom severity between delayed versus no antibiotic prescribing, and delayed versus immediate antibiotic prescribing.

Most of the studies took place in primary care settings with the average age of study participants ranging from 2.7 to 51.7 years.

The researchers accounted for factors including age, sex, previous duration of illness, severity of symptoms, smoking status and underlying conditions. Average symptom severity was measured two to four days after initial consultation on a seven point scale (ranging from normal to as bad as could be).

The researchers found no difference in symptom severity for delayed versus immediate antibiotics or delayed versus no antibiotics.

Symptom duration was slightly longer in those given delayed versus immediate antibiotics (11.4 v 10.9 days), but was similar for delayed versus no antibiotics.

Complications resulting in hospital admission or death were lower with delayed versus no antibiotics and delayed versus immediate antibiotics, but neither result was statistically significant.

Re-consultation rates were significantly reduced and an increase in patient satisfaction were found for delayed versus no antibiotics, but not for delayed versus immediate antibiotics.

Children under 5 years of age showed slightly more severe symptoms with delayed antibiotics than with immediate antibiotics, but this was not considered to be clinically meaningful, and this was not seen in older age groups.

 hey concluded that delayed antibiotic prescribing “appears to be a safe and effective strategy for most patients, including those in higher risk subgroups.”

This was a large, detailed analysis accounting for differences in study design and quality to reduce bias. The researchers nevertheless pointed out some limitations, being unable to exclude the possibility that other unmeasured factors may have affected their results.

Source: Medical Xpress

Journal information: Beth Stuart et al, Delayed antibiotic prescribing for respiratory tract infections: individual patient data meta-analysis, BMJ (2021). DOI: 10.1136/bmj.n808

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WHO Says New Antibiotic Treatments are Falling Behind

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The development projects of new antibiotic treatments are falling behind, despite increasing awareness of the antibiotic resistance threat, according to a recently released report by the World Health Organization. 

The WHO revealed that none of the 43 antibiotics that are currently in clinical development sufficiently address the problem of drug resistance in the world’s most dangerous bacteria.

Dr Hanan Balkhy ,Assistant Director General on AMR, WHO said that, “The persistent failure to develop, manufacture, and distribute effective new antibiotics is further fueling the impact of antimicrobial resistance (AMR) and threatens our ability to successfully treat bacterial infections.”

All of the new antibiotics released onto the market in the past few decades have been variations of those developed in the 1980s.

The impact of AMR is most severely felt in resource-constrained settings and in vulnerable populations such young children. Bacterial pneumonia and bloodstream infections are some of the major causes of childhood mortality under age 5, and about 30% of neonates with sepsis die due to bacterial infections resistant to multiple first-line antibiotics.

WHO puts out its Antibacterial Pipeline Report every year, reviewing antibiotics under development. The report evaluates the potential of the candidates to address the most threatening drug-resistant bacteria outlined in the WHO Bacterial Priority Pathogens List (WHO PPL). Since it began in 2017, this list, which includes 13 priority drug-resistant bacteria, has informed and guided priority areas for research and development.

The 2020 report paints a picture of an almost stalled pipeline with only few antibiotics in recent years receiving regulatory approval. Most of these agents in development have little extra clinical benefit over current ones, with 82% of recently approved antibiotics being derivatives of previous  ones with well-established drug-resistance, and drug resistance to these new ones is expected to emerge rapidly.

The review concludes that “overall, the clinical pipeline and recently approved antibiotics are insufficient to tackle the challenge of increasing emergence and spread of antimicrobial resistance”.

Speeding up development requires innovative approaches. For the first time. the 2020 WHO pipeline report includes a comprehensive overview of non-traditional antibacterial medicines, detailing 27 antibacterial agents in the pipeline. These range from antibodies to bacteriophages and therapies that boost the immune response and weaken bacterial effects.

The report notes that there are some promising products in different stages of development. However, only a fraction of these will ever make it to the market due to the economic and inherent scientific challenges in the drug development process. This, along with the small return on investment from successful antibiotic products, has limited the interest of major private investors and most large pharmaceutical companies.

Only a fraction of the promising products in the pipeline will make it to market because of financial and scientific obstacles in the development process. 

The preclinical and clinical pipelines continue to be driven by small- and medium-sized companies, which often struggle to finance their products through clinical trials and approval.

The COVID pandemic has deepened the global understanding of the health and economic implications of uncontrolled disease, as well as funding gaps, including investments in R&D of antimicrobial medicines and vaccines, while also demonstrating that much can be achieved with political will and sufficient funding.

“Opportunities emerging from the COVID-19 pandemic must be seized to bring to the forefront the needs for sustainable investments in R&D of new and effective antibiotics,” said Haileyesus Getahun, Director of AMR Global Coordination at WHO. “Antibiotics present the Achilles heel for universal health coverage and our global health security. We need a global sustained effort including mechanisms for pooled funding and new and additional investments to meet the magnitude of the AMR threat.”

To address funding challenges in antibiotics development, WHO partnered with the Drugs for Neglected Diseases intitive (DNDi) to set up the Global Antibiotic R&D Partnership (GARDP) to develop promising treatments.

In addition, the WHO has been working closely with other non-profit funding partners such as the CARB-X to “push” and accelerate antibacterial research. Another important new initiative is the AMR Action Fund, a partnership by the European Investment Bank. pharmaceutical companies and philanthropies.

Source: News-Medical.Net

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Harnessing Tailocins, Antibacterial ‘Homing Missiles’

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A Berkeley Lab-led team is investigating how to harness tailocins, antibacterial nanomachine ‘weapons’ akin to phages but produced by certain bacteria in suicide attacks against other strains.

“Tailocins are extremely strong protein nanomachines made by bacteria,” explained Vivek Mutalik, a research scientist at Lawrence Berkeley National Laboratory (Berkeley Lab) who studies tailocins and phages, the bacteria-infecting viruses that tailocins appear to be remnants of. “They look like phages but they don’t have the capsid, which is the ‘head’ of the phage that contains the viral DNA and replication machinery. So, they’re like a spring-powered needle that goes and sits on the target cell, then appears to poke all the way through the cell membrane making a hole to the cytoplasm, so the cell loses its ions and contents and collapses.”

Many bacteria can produce tailocins, seemingly under stress conditions. However, the tailocins are only lethal to specific strains, and seem to be used by bacteria to compete with rivals. Since they are so similar to phages, scientists believe that tailocins are repurposed from DNA that was injected into bacterial genomes from viral infections.

According to Mutalik, tailocins kill the bacteria that produce them as they erupt through the membrane, much the way replicated viruses do. However, once released, the tailocins selectively target certain strains and not the host lineage cells.

“They benefit kin but the individual is sacrificed, which is a type of altruistic behavior. But we don’t yet understand how this phenomenon happens in nature,” Mutalik commented. Scientists also don’t know precisely how the stabbing needle plunger of the tailocin functions.

These topics, and tailocins as a whole, are an area of hot research due to the many possible applications. Mutalik and his colleagues in Berkeley Lab’s Biosciences Area along with collaborators at UC Berkeley are interested in harnessing tailocins to better study microbiomes. Other groups are keen to use tailocins as an alternative to traditional antibiotics -which indiscriminately wipe out beneficial strains alongside the bad and are increasingly ineffective due to the evolution of drug-resistance traits.
There is also great interest in using tailocins as an alternative to antibiotics, due to increasing antibiotic resistance and the fact that conventional antibiotics wipe out beneficial strains along with the disease-causing ones.

In their most recent paper, the collaborative Berkeley team explored the genetic basis and physical mechanisms governing how tailocins attack specific strains, and looked at genetic similarities and differences between tailocin producers and their target strains.

Upon examination of 12 strains of tailocin-using soil bacteria, the researchers found that differences in the lipopolysaccharides on the outer membranes determined whether they were targeted by a particular tailocin.

“The bacteria we studied live in a challenging, resource-poor environment, so we’re interested to see how they might be using tailocins to fight for survival,” said co-lead author Adam Arkin, a senior faculty scientist in the Biosciences Area and technical co-manager of the Ecosystems and Networks Integrated with Genes and Molecular Assemblies (ENIGMA) Scientific Focus Area. Arkin observed that although bacteria can easily be induced to produce tailocins in the lab, as well as scale up for mass production for medicinal applications, it is not well understood how bacteria deploy tailocins in their natural environment, and how or why particular strains are so precisely targeted.

“Once we understand the targeting mechanisms, we can start using these tailocins ourselves,” Arkin added. “The potential for medicine is obviously huge, but it would also be incredible for the kind of science we do, which is studying how environmental microbes interact and the roles of these interactions in important ecological processes, like carbon sequestration and nitrogen processing.”

At the moment, it is difficult to observe what is happening in a bacterial community, but tailocins could remove individual strains with precision to allow a better understanding of the situation.

Follow-up studies being conducted involve taking atomic-level images of the taolicins in action.

Source: SciTech Daily

Journal information: “Systematic discovery of pseudomonad genetic factors involved in sensitivity to tailocins” by Sean Carim, et al., 1 March 2021, The ISME Journal. DOI: 10.1038/s41396-021-00921-1

Categories : Diseases, Syndromes and ConditionsTags :

Premature Death Risk Doubled for Patients With Superbug on Their Skin

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Adults middle-aged or older who carry methicillin-resistant Staphylococcus aureus (MRSA) ‘superbug’ on their skin are twice as likely to die within the next decade as people who do not, according to a study by the University of Florida (UF).

“Very few people who carry MRSA know they have it, yet we have found a distinct link between people with undetected MRSA and premature death,” said lead author Arch Mainous, PhD, a professor in the department of health services research, management and policy at UF.

The findings suggest that routine screening for undetected MRSA may be warranted in older people to prevent deaths from infection.

A third of Americans carry Staphylococcus aureus, or staph, on their skin or in nasal passages, and of these about 1% carry MRSA, the notorious antibiotic resistant staph strain.

MRSA carriers may not even be aware that they carry the bacteria unless they develop an infection or are tested for it. A quarter of people who carry MRSA without an active infection, known as colonised MRSA for at least a year, eventually develop a MRSA infection.

“MRSA can be part of normal body flora, but it can lead to infection when immune systems are compromised, especially in people who are hospitalized, have underlying disease, or after antibiotic use,” said Prof Mainous, also vice chair for research in the UF College of Medicine’s department of community health and family medicine.

According to a 2017 Centers for Disease Control and Prevention report, 119 000 Americans experienced a staph bloodstream infection and nearly 20 000 died. Hospitalised patients with colonised MRSA may be particularly vulnerable to  infection in hospital or after discharge. Among carriers, wounds, surgical incisions and use of medical devices, such as catheters, may also lead to MRSA infection.

In this study, researchers analysed data from the 2001-2004 National Health and Nutrition Examination Survey, a nationally representative study combining survey questions with laboratory testing, which includes nasal swabs for detecting MRSA.

Adjusting for risk factors including gender and ethnicity, the researchers linked data on participants ages 40-85 with data from the National Death Index to track deaths over an 11-year period.

The mortality rate among participants without MRSA was about 18% compared with 36% among those with colonised MRSA. There was no increased mortality risk for those with non-MRSA staph bacteria on their skin.

Although some states and hospital systems require MRSA testing for patients before hospital admission, policies for testing and treatment of colonised MRSA, which may include antibiotics use, vary widely betweens hospitals, Prof Mainous said.

“Without a uniform strategy, we are missing an opportunity to help prevent deaths caused by MRSA,” he said. “Maybe we should know who is carrying MRSA.”

Source: Medical-News.Net

Journal information: Mainous, A. G., et al. (2021) Methicillin-Resistant Staphylococcus Aureus Colonization and Mortality Risk Among Community Adults Aged 40-85. Journal of the American Board of Family Medicine.

Categories : Diseases, Syndromes and Conditions Expert OpinionTags :

Microbes Develop Resistance to Disinfectant Too, Warns UFS Professor

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News-Medical.Net interviewed Professor Robert Bragg of the University of the Free State on the topic of pathogens, particularly bacteria, developing resistance to common disinfectants.

Professor Robert Bragg said that the control of diseases rests on three pillars: 1) vaccinations and vaccines, 2) treatment options (such as antibiotics for bacterial diseases), and 3) biosecurity.

Proff Brage explained that 10 to 15 years ago, there was an assumption that bacteria would not evolve resistance against disinfectants, but the COVID pandemic prompted a rethink. Now, disinfectant resistance is being looked at in the same light as antibiotic resistance. Biosecurity, he said, is ensuring that individuals do not come into contact with the pathogens in the first place. This is easily seen in the COVID pandemic, where face masks are worn (with a protection against contracting the disease of up to 70%), social distancing is enforced and hands and surfaces are sanitised. Though Prof Bragg’s main area of research is not antibiotic resistance, he notes that, “There are resistance mechanisms that are shared between antibiotics and disinfectants and we are looking at how these mechanisms increase resistance to disinfectants.” 

The protection of antibiotics is something taken for granted, but although mostly easily treatable (for now), bacteria can spread much faster than viruses, which require cells to reproduce in and whose re[plication rate is measured in days. “A common well-known bacterium such as Escherichia coli has a doubling time of around 20 min under ideal conditions. In other words, it only takes just 20 minutes for a population of E. coli to go from 1 million to 2 million and another 20 mins to reach 4 million, and so on,” Prof Bragg said. In the post-antibiotic era, there would be some treatment options such as bacteriophages, but for livestock the best protection would be biosecurity. However, disinfectant resistance would reduce the effectiveness of that option.

His research team has conducted a number of studies into the mechanisms of bacterial disinfectant resistance. “My research team has been working on various aspects of efficacy and resistance to disinfectants for quite some time and we have various projects that are currently underway,” he said. “Recently we identified a highly resistant strain of a Serratia species of bacteria. This strain was substantially more resistant to many different disinfectants than the reference strain. This great difference in the levels of susceptibility has allowed us to investigate various possible research mechanisms and also to look for possible novel resistance mechanisms.”

One of his team’s discoveries was that this highly resistant bacteria strain could grow on disinfectant if it was the sole source of carbon. Other areas of research around the resistant strain include sequencing and analysis of its genome, the role of bacterial efflux pumps removing disinfectant, and the role of plasmids (vehicles of genetic transfer between bacteria) in resistance and whether they are transferrable.

With regard to viruses, there are two kinds of viruses, enveloped and naked, and disinfectant has different effects on them. Enveloped viruses such as SARS-CoV-2, have a lipid layer picked up from their host cell, and are easy to kill with simple disinfectants because they break up the lipid layer, killing the cell. Naked cells are much harder to kill, and the few disinfectants that work against them are thought to do so by somehow disrupting the virus’ receptors.

One sanitiser of concern is alcohol, where 70% is considered optimal. However, people believe that ‘more is better’, yet increasing the alcohol percentage actually makes it evaporate faster, reducing contact time and thus leaving more of the virus behind. Similarly, some sanitisers include low levels of other disinfectant substances which are below the minimum threshold to kill the pathogens. This can leave surviving bacteria to develop resistance against these other sanitisers.

Prof Bragg advised that the public should purchase and use sanitisers prudently, following their instructions for use appropriately, and preferably checking to see if they are registered. He also cautioned

Source: News-Medical.Net

Categories : Diseases, Syndromes and ConditionsTags :

International Travellers at Risk of MDR Bacteria

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International travellers are at risk of picking up a number of drug-resistant pathogens, according to a new European study.

In the COVID pandemic, international travel has become a distant memory for most of those used to it. As restrictions are lifted and international travel resumes, travellers are still at risk from other dangerous pathogens. In recent years, the rise of intestinal multidrug resistant gram-negative (MDR-GN) bacteria around the world poses a serious health threat, with MDR clones of E.coli and Klebsiella pneumoniae threatening more antibiotic resistant infections around the world. The spread of MDR-GN is a known threat in long-term care facilities, with residents forming a reservoir for the microbes but is also common in international travel as well. It is well documented that international travel results in the spread of multidrug-resistant E. coli, with up to 80% of travellers returning from high-risk regions being colonised by MDR-GN bacteria for up to a year. However, the existing research only compared participants before and after travel. A group of researchers from Universities of Basel, Birmingham, Helsinki and Oslo, and the Wellcome Sanger Institute set out to investigate the spread of such bacteria on a day by day basis.

Over a period of three weeks, the researchers monitored the health of a group of European travellers in the Lao People’s Democratic Republic by analysing daily information returns and stool samples. They found that by the end of the study period, 70% of the travellers had been colonised. The bacterial strains colonised travellers staying at the same hotel and spending time in one another’s company. In one case, a participant was colonised by taking a shower in another’s bathroom.

“International travel is strongly linked to the spread of MDR-GN bacteria, with transmission highest in India and Southeast Asia, Africa and South America,” said senior study author Professor Alan McNally, University of Birmingham. “Travellers visiting these high-risk regions are at substantial risk of acquiring the bacteria. Colonisation by MDR-GN bacteria is a highly dynamic process. We found constant ‘competition’ between circulating strains acquired by individual hosts and the travelers’ ‘native’ bacteria. Travellers can pick up the bacteria even during short visits and further spread the strains after returning home.”

All of the participants had acquired extended-spectrum beta-lactamases (ESBL) during their stay in Laos. ESBL enzymes create resistance within the body to most beta-lactam antibiotics, including penicillins, cephalosporins, and aztreonam. Infections with ESBL-producing organisms have proved difficult to treat. Also, all but one participant acquired multiple strains of bacteria with 83 unique strains identified (53 E. coli, 10 Klebsiella, 20 other ESBL-GN species), with up to four other participants sharing strains.

Study co-senior author, Professor Jukka Corander, at the University of Oslo and the Wellcome Sanger Institute, commented: “Our study reveals the true scale and complexity at which drug-resistant bacteria colonise the intestinal tract during travel, demonstrating that it has been seriously underestimated previously.

“In addition, several of our participants lost some of their travel-acquired ESBL-GN strains while still abroad – indicating that previous studies solely employing pre- and post-travel sampling have under-reported the extent to which travellers are colonised by ESBL-GN.”

Source: News-Medical.Net

Journal information: Kantele, A., et al. (2021) Dynamics of intestinal multidrug-resistant bacteria colonisation contracted by visitors to a high-endemic setting: a prospective, daily, real-time sampling study. The Lancet Microbe. doi.org/10.1016/S2666-5247(20)30224-X.

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Prevalence of Antibiotic Resistance is Underestimated

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Antibiotic resistance to pathogenic bacteria in humans has spread farther than expected, as it has been discovered that bacteria can swap DNA far more readily than thought possible.

A growing threat, antibiotic resistance has emerged faster than thought possible. Some 33 000 deaths have occurred to antibiotic resistant infections in Europe alone, and finding new antibiotics or even alternatives are a top research priority. Totally different strains of bacteria can swap genetic information through the use of containers called plasmids. Plasmids are small containers of DNA which are kept outside of their chromosomes. When two bacteria come into contact, they can copy plasmids to one another in a process called conjugation (also known as “bacterial sex“). This is the most important means by which bacteria spread antibiotic resistance.

“In recent years, we’ve seen that resistance genes spread to human pathogens to a much greater degree than anyone expected,” said Jan Zrimec, a researcher in systems and synthetic biology at the Chalmers University of Technology. “Many of the genes appear to have originated in a wide array of bacterial species and environments, such as soil, water, and plant bacteria.

“This has been difficult to explain because although conjugation is very common, we’ve thought that there was a distinct limitation for which bacterial species can transfer plasmids to each other. Plasmids belong to different mobility groups or MOB groups, so they can’t transfer between just any bacterial species.”

Among his developments, he has written an algorithm that can sift through substantial amounts of plasmid DNA to pick out sections of DNA which are necessary for conjugation (known as oriT regions, where the enzyme relaxase can bind to and snip out DNA). This algorithm can then sort the plasmids into groups based on their oriT regions. His new method differs from the standard one because it analyses oriT regions by their physiochemical properties instead of searching DNA for the enzyme sequence for relaxase, or the point where it can bind to. This method is less time-consuming and resource intensive than the standard one.

Previously, it was thought that a plasmid had to have both the relaxase enzyme and the oriT sequence to bind to, but a bacterial cell can have an oriT region for conjugation to occur. With his new algorithm, he has been able to explore the DNA of 4600 plasmids from different bacteria found in nature.
– There may be eight times as many oriT regions than those discovered with standard methods.
– There may be twice as many mobile plasmids as previously known.
– There also may be twice as many bacterial species with mobile plasmids as previously known.
– More than half the plasmids have an oriT group matching to an enzyme for conjugation from a plasmid that already been classified in a different MOB group. This means that they could be transferred from a different plasmid in the same cell.

The last finding suggests that there may be far greater interchange between bacteria than had been previously been believed.

“This has been a major limitation of the research field up to now,” Zrimec said. “I hope that the methods will be able to benefit large parts of the research into antibiotic resistance, which is an extremely interdisciplinary and fragmented area. The methods can be used for studies aiming to develop more effective limitations to antibiotic use, instructions for how antibiotics are to be used, and new types of substances that can prevent the spread of resistance genes at the molecular level.”

Source: News-Medical.Net

Journal information: Zrimec, J. (2021) Multiple plasmid origin‐of‐transfer regions might aid the spread of antimicrobial resistance to human pathogens. MicrobiologyOpen.doi.org/10.1002/mbo3.1129.

Categories : AntibioticsTags :

Single Water Molecule Is the Key to Macrolide Resistance

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High resolution molecular structures produced by researchers at the University of Illinois Chicago show that the effectiveness of the macrolides class of antibiotics – and bacterial resistance to it – depends on interaction with a single water molecule. 

Macrolides have a broad spectrum of use against most gram-positive bacteria and are a widely used treatment  for a variety of infections. Clarithromycin, for example, is used as a mainstay treatment for respiratory infections. Due to antibiotic overuse, antibiotic resistance has emerged Macrolides interrupt protein biosynthesis in the ribosomes of pathogenic bacteria, and are one of the most successful classes of antibiotics to use this mechanism of action. The macrolides accomplish this by entering the cell and binding to the bacteria’s ribosomes, preventing them from manufacturing and releasing new proteins. As a result of the halt in protein synthesis, the bacteria can no longer grow or replicate. However, mutations came about that rendered the bacteria resistant.

Seeking to understand how the bacteria came about their resistance, the researchers learned how to capture images of the ribosome and the macrolide invading it. The researchers discovered that precisely one water molecule was required for the antibiotic to bind to the ribosome.

Corresponding author Yury Polikanov, associate professor of biological sciences at UIC, said: “We compared the hi-res structures of the ribosomes from sensitive and resistant bacteria and noticed that a water molecule that is needed for the tight antibiotic binding was not present in the ribosomes from the drug-resistant bugs. In the ribosomes from the drug-resistant bacteria, there was simply no room for this water molecule.”

The mutation that conferred macrolide resistance adds a pair of methyl groups to where the macrolide molecule normally binds to the ribosome, and the water molecule instead disrupts the binding.  

“We are very much excited by this discovery,” Polikanov said. “Because we now know how exactly macrolide antibiotics interact with their target, the ribosome. This discovery is important because it will inform and facilitate the development of new antibiotics that do not need this water molecule for binding. There is a huge demand for such drugs that are able to kill even those bacteria that became resistant to the currently used drugs.”

Source: News-Medical.Net

Journal information: Svetlov, M.S., Syroegin, E.A., Aleksandrova, E.V. et al. Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance. Nat Chem Biol (2021). https://doi.org/10.1038/s41589-020-00715-0

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Antibiotic Overuse by Children’s Hospitals Contributing to Antibiotic Resistance

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Children’s hospitals may be contributing to antibiotic resistance by overprescription of antibiotics, according to a recent study.

The study, conducted by the University of Alabama at Birmingham (UAB),   found that in 51 children’s hospitals across the United States, rates of antibiotic administration ranged from 22% to 52%. Approximately a quarter of children receiving antibiotics were receiving them incorrectly. This adds to a growing body of evidence that points to antibiotics overuse and misuse by children’s hospitals – which ought to know better.Study co-author, Dr Jason Newland said, “There’s no doubt: We’ve seen some extra use of antibiotics, The impact of the pandemic on antibiotic use will be significant.

“The study’s numbers are likely an underestimate since the research involved 32 children’s hospitals already working together on proper antibiotic use. Newland said the US’ more than 250 children’s hospitals need to improve. Even though COVID fears have reduced the numbers of children’s hospital visits, antibiotics are still being prescribed via telemedicine.

“I hear a lot about antibiotic use for the ‘just in case’ scenarios,” said Dr Joshua Watson, at Nationwide Children’s Hospital in Ohio. “We underestimate the downsides.”

Dr Shannon Ross, an associate professor of paediatrics and microbiology at UAB, said that not all doctors have been taught the correct use of antibiotics. Regarding this overuse, she said, “Many of us don’t realize we’re doing it. It’s sort of not knowing what you’re doing until someone tells you.”
Unnecessary antibiotic use is a problem, and the pandemic “has thrown a little bit of gas on the fire,” said Dr Mark Schleiss, a paediatrics professor at the University of Minnesota Medical School.

“It’s irresponsible,” said Christina Fuhrman, who almost lost her infant daughter to a Clostridium difficile infection, and who now advocates for correct antibiotic use. Along with parents begging for antibiotics in paediatricians’ offices, the situation is “creating a monster.”
Many studies have attested to the rise of C. diff in children, which causes gastrointestinal problems. A 2017 study found that cases of a certain multidrug-resistant Enterobacteriaceae type rose 700% in American children in just eight years. And a steady stream of research points to the stubborn prevalence in kids of the better-known MRSA, or methicillin-resistant Staphylococcus aureus.

“It’s getting more and more worrisome,” said Ross. “We have had patients we have not been able to treat because we’ve had no antibiotics available.”

Source: News-Medical.Net

Journal information: Tribble A, Lee B, Flett K et al. Appropriateness of Antibiotic Prescribing in United States Children’s Hospitals: A National Point Prevalence Survey. Clinical Infectious Diseases. 2020;71(8):e226-e234. doi:10.1093/cid/ciaa036