Researchers have used explainable artificial intelligence (explainable AI) to find structurally new antibiotics with minimal toxicity. They reported their findings online in Nature on Dec. 20, 2023. In animal testing, compounds identified via the method showed that they had activity against drug-resistant gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), one of the most serious bacterial public health threats.
Mission Bio Inc. released its Tapestri single-cell minimal residual disease (MRD) assay for acute myeloid leukemia (AML) on September 26, with the goal of enabling greater personalization of care for patients with blood cancers. The test can provide insights into the progression of AML and help identify targets for treatment in addition to identifying patients truly experiencing relapse as distinct from having pre-leukemic or precursor clones.
A newly discovered antibiotic has been shown to block the synthesis of bacterial cell walls via immutable targets, raising the prospect of a class of drugs that will not lose effect through the development of antimicrobial resistance. Clovibactin, isolated from soil bacteria, targets the cell wall precursor molecules lipid II, lipid III and undecaprenyl phosphate (C55PP), all of which have a pyrophosphate group in common.
Researchers from the U.S. National Institutes of Health and collaborators recently conducted a study investigating the mechanisms of HIV-1 resistance to integrase strand transfer inhibitors (INSTIs), such as the approved drug dolutegravir (DTG). They focused on understanding the mechanisms of resistance caused by mutations at positions 138, 140, and 148 and analyzed combinations of the mutations E138K, G140A/S, and Q148H/K/R, all conferring resistance to INSTIs.
A different class of antibiotics could ease the increasing resistance triggered by some gram-negative bacteria. LpxC inhibitors are not new, but all attempts to develop them have failed due to cardiovascular toxicity or ineffectiveness. A modification of the structure of these compounds may have solved the problem. Duke University scientists demonstrated the preclinical safety and efficacy of an LpxC inhibitor candidate against a wide selection of these pathogens.
Bacteria cells are masters of adaptation and evolution, and by better understanding how they adapt and evolve, researchers hope to develop better drugs to fight microbial resistance, which is increasingly becoming a global public health threat. Researchers from the antimicrobial resistance interdisciplinary research group at the Singapore-MIT Alliance for Research and Technology (SMART) sought to understand the mechanisms bacteria use to adapt against stressors, and they discovered a new stress signaling system that sheds light on a new mechanism of antimicrobial resistance.
Researchers at the Barcelona Institute of Science and Technology’s Center for Genomic Regulation (CRG) and Pulmobiotics Ltd. have used one bacterium to fight another. In mouse models, the team used engineered Mycoplasma pneumoniae to treat Pseudomonas aeruginosa, the chief culprit in ventilator-associated pneumonia (VAP).
When a drug prevents bacteria from synthesizing their own folate, an essential compound for their survival, they take it directly from the host. This antibiotic resistance mechanism had not been detected until now because bacteria behave differently in the laboratory than they do in vivo during an infection.
When a drug prevents bacteria from synthesizing their own folate, an essential compound for their survival, they take it directly from the host. This antibiotic resistance mechanism had not been detected until now because bacteria behave differently in the laboratory than they do in vivo during an infection.
P-glycoprotein (P-gp) is a multidrug resistance (MDR)-associated protein, which is widely distributed in membranes of several cells including hepatocytes, renal proximal tubular cells and brain capillary endothelial cells. The overexpression of this drug efflux transporter protein is considered to play a key role in the development of MDR.
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