Short chain α-pyrones capable of potentiating penicillin G against Pseudomonas aeruginosa.

The dramatic increase in bacterial resistance over the past three decades has greatly reduced the effectiveness of nearly all clinical antibiotics, bringing infectious disease to the forefront as a dire threat to global health. To combat these infections, adjuvant therapies have emerged as a way to reactivate known antibiotics against resistant pathogens. Herein, we report the evaluation of simplified α-pyrone adjuvants capable of potentiating penicillin G against Pseudomonas aeruginosa, a Gram-negative pathogen whose multidrug-resistant strains have been labeled by the Centers for Disease Control and Prevention as a serious threat to public health.

Development of a Robust and Quantitative High-Throughput Screening Method for Antibiotic Production in Bacterial Libraries.

Over the past 30 years, there has been a dramatic rise in the number of infections caused by multidrug-resistant bacteria, which have proliferated due to the misuse and overuse of antibiotics. Over this same time period, however, there has also been a decline in the number of antibiotics with novel mechanisms of action coming to market. Therefore, there is a growing need for an increase in the speed at which new antibiotics are discovered and developed.

Substituent Effects on the Coordination Chemistry of Metal-Binding Pharmacophores.

A combination of XAS, UV-vis, NMR, and EPR was used to examine the binding of a series of α-hydroxythiones to CoCA. All three appear to bind preferentially in their neutral, protonated forms. Two of the three clearly bind in a monodentate fashion, through the thione sulfur alone.

Characterization of a highly efficient antibiotic-degrading metallo-β-lactamase obtained from an uncultured member of a permafrost community.

Antibiotic resistance is a major global health problem, one that threatens to derail the benefits garnered from arguably the greatest success of modern medicine, the discovery of antibiotics. Among the most potent agents contributing to antibiotic resistance are metallo-β-lactamases (MBLs). The discovery of MBL-like enzymes in microorganisms that are not in contact with the human population is of particular concern as these proteins already have the in-built capacity to inactivate antibiotics, even though they may not need MBL activity for their survival.

AIM-1: An Antibiotic-Degrading Metallohydrolase That Displays Mechanistic Flexibility.

Antibiotic resistance has emerged as a major threat to global health care. This is largely due to the fact that many pathogens have developed strategies to acquire resistance to antibiotics. Metallo-β-lactamases (MBL) have evolved to inactivate most of the commonly used β-lactam antibiotics.