β-Lactam antibiotics were the earliest discovered and are the most widely used group of antibiotics that work by inactivating penicillin-binding proteins to inhibit peptidoglycan biosynthesis. As one of the most efficient defense strategies, many bacteria produce β-lactam-degrading enzymes, β-lactamases, whose biochemical functions and regulation have been extensively studied. A signal transduc...

The four-membered cyclic amides commonly known as 2-azetidinones or β-lactams occupy a prominent place in the realm of organic and medicinal chemistry since the structure elucidation of penicillin showed the presence of β-lactam ring in it and the antibacterial activity of penicillin was attributed to the presence of β-lactam ring. The early investigations in organic chemistry were focused on d...

Active efflux of antimicrobial agents is a primary mechanism by which bacterial pathogens can become multidrug resistant. The combined use of efflux pump inhibitors (EPIs) with pump substrates is under exploration to overcome efflux-mediated multidrug resistance. Phenylalanine-arginine β-naphthylamide (PAβN) is a well-studied EPI that is routinely combined with fluoroquinolone antibiotics, but ...

Background & Aims: The production of extended-spectrum-β-lactamases (ESBLs) is the main mechanism of resistance to β-lactam antibiotics. The outbreak of isolates simultaneously possessing several resistance mechanisms to β-lactam antibiotics caused a decrease in sensitivity of the confirmatory tests for ESBL. The aim of this study was the evaluation of the β-lactamase disk test...

Spermine (Spm), a potent bactericidal polyamine, exerts a strong synergistic effect with βlactams against methicillin-resistant Staphylococcus aureus (MRSA) in a pH-dependent manner. At high pH (>8) Spm is a potent nucleophile, and able to form Spm-β-lactam adduct. At physiological pH (or lower), Spm carries positive charges, and can bind to DNA through charge interactions. The potential of Spm...

AmpC β-lactamase confers resistance to β-lactam antibiotics in many Gram negative bacteria. Inducible expression of AmpC requires an N-acetylglucosaminidase termed NagZ. Here we describe the synthesis and characterization of hydroxyazepane inhibitors of NagZ. We find that these inhibitors enhance the susceptibility of clinically relevant Pseudomonas aeruginosa to β-lactams.

Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that mainly causes otitis media in children and community-acquired pneumonia or exacerbations of chronic obstructive pulmonary disease in adults. A large variety of studies suggest that biofilm formation by NTHi may be an important step in the pathogenesis of this bacterium. However, the underlying mechanisms involved in thi...

Due to the emerging resistance against classical β-lactam-based antibiotics, a growing number of bacterial infections has become harder to treat. This alarming tendency necessitates continued research on novel antibacterial agents. Many classes of β-lactam antibiotics are characterized by the presence of the 3-aminoazetidin-2-one core, which resembles the natural substrate of the target penicil...

During cefoxitin-based nasal screening, phenotypically categorized methicillin-resistant Staphylococcus aureus (MRSA) was isolated and tested negative for the presence of the mecA and mecC genes as well as for the SCCmec-orfX junction region. The isolate was found to carry a mecB gene previously described for Macrococcus caseolyticus but not for staphylococcal species. The gene is flanked by β-...