Tag: antibiotic resistance

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Single Water Molecule Is the Key to Macrolide Resistance

On By ModernMedia

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

On By ModernMedia

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