Acinetobacter baumanniiSeveral clusters of bacteria are shown at 24,730x magnification. Acinetobacter Members of the genus are nonmotile bacilli 1–1.5 μm in diameter and 1.5–2.5 μm in length that become spherical during the stationary phase of growth. This bacterium is oxidase negative, so it does not use oxygen for energy production. When enlarged, they may appear in pairs. Acinetobacter genusis widely distributed in nature and is a resident flora of the skin. Some members of this genus are important because they are an emerging cause of nosocomial pulmonary infections, ie, pneumonia, blood disorders, and wound infections. Treatment of infections caused by A. baumannii is becoming increasingly difficult as this organism has developed considerable antimicrobial resistance. The only drug that acts on multidrug-resistant strains of A. baumannii is colistin, which is a highly toxic drug. “/>
A new experimental antibiotic could easily fight off one of the world’s most notoriously drug-resistant and deadly bacteria, at least in lab dishes and mice. It does so in a way never seen before, opening up a whole new class of drugs that could lead to new treatments that are more desperately needed to fight drug-resistant infections.
This week, the survey results pair of paper The paper, published in the journal Nature, describes extensive drug development research conducted by researchers at Harvard University and the Swiss-based pharmaceutical company Roche.
In an accompanying commentary, chemists Morgan Gugger and Paul Hagenroter of the University of Illinois at Urbana-Champaign write that more than 50 years after the Food and Drug Administration approved a new class of antibiotics against bacteria, He optimistically discussed this finding, pointing out that Categories of bacteria that this drug targets: Gram-negative bacteria. This category includes enteric pathogens such as: Escherichia coli, Salmonella, Staphylococcus ruberBacteria that cause diseases such as chlamydia, bubonic plague, gonorrhea, whooping cough, cholera, and typhoid fever are extremely difficult to kill because they have complex membrane structures that block most drugs.Accumulate other drug resistance strategies
significant discovery
In this case, a new drug called zoslavalpine fights Gram-negative bacteria. Carbapenem resistance Acinetobacter baumanniialso known as crab. It may sound confusing, but it is an opportunistic invasive bacterium that frequently attacks hospitalized and critically ill patients and causes deadly infections around the world. There is widespread drug resistance; Pan-resistant strains continue to emerge In other words, strains of bacteria that are resistant to all currently available antibiotics. Mortality rates for invasive CRAB infections range from 40 to 60%. In 2017, the World Health Organization listed it as: Priority 1: Critical Pathogens for which new antibiotics are most urgently needed.
Zoslavalpine could end up being an urgently needed drug, as Gugger and Hergenroter write in their commentary: “Zoslavalpine is already being tested in clinical trials. The future looks promising, given that a new class of antibiotics may finally be available for invasive CRAB infections. ”
An international team of researchers led by Roche’s Michael Lobritz and Kenneth Bradley, For the first time, a precursor to zoslavalpine was identified through an unusual screen.. Most new antibiotics are small molecules, meaning they have a molecular weight of less than 600 daltons. But in this case, the researchers searched a collection of 45,000 larger, heavier compounds called tethered macrocyclic peptides (MCPs), which have a molecular weight of about 800 daltons. The molecules were screened against a collection of Gram-negative bacterial strains. A. Baumani distortion. A series of compounds knocked back bacteria, and the researchers selected the top compound with a convenient handle: RO7036668. The molecules were then optimized and fine-tuned, including charge balance, to make them more effective, soluble, and safe. The result was Zoslavalpine.
powerful drug
In further experiments, zoslavalpine proved effective in killing a collection of 129 clinical CRAB isolates, many of which were difficult-to-treat isolates. The experimental drug was also effective in eliminating pan-resistant bacterial infections in mice. A. Baumani This means that no matter how the drug works, it may be able to circumvent existing resistance mechanisms.
The researchers then set out to find out: how Zoslavalpine killed these resistant and deadly bacteria. They did this using the standard method of exposing bacteria to varying concentrations of antibiotics to induce spontaneous mutations. For the bacteria that developed resistance to zoslavalpine, the researchers used whole-genome sequencing to determine where the mutations were located. They found 43 different mutations, most of them in genes encoding LPS transport and biosynthetic machinery.