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.
While simultaneous targeting of PD-1 and TGF-β has been previously suggested to be a favorable strategy to reverse immune checkpoint inhibitor (ICI) resistance of tumors, the hydrophobicity of TGF-β inhibitors and latent drug-related adverse events of this treatment hindered its utility.
To jumpstart the development of much-needed antibiotics, the European Federation of Pharmaceutical Industries and Associations (EFPIA) released a new report Sept. 28 demonstrating the economic benefit of granting additional exclusivity for another drug as a way of incentivizing antibiotic R&D.
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