Antimicrobial effects of novel siderophores linked to beta-lactam antibiotics.

As a strategy to increase the penetration of antibiotic drugs through the outer membrane of gram-negative pathogens, facilitated transport through siderophore receptors has been frequently exploited. Hydroxamic acids, catechols, or very close isosteres of catechols, which are mimics of naturally occurring siderophores, have been used successfully as covalently linked escorting moieties, but a much wider diversity of iron binding motifs exists. This observation, coupled to the relative lack of specificity of siderophore receptors, prompted us to initiate a program to identify novel, noncatechol siderophoric structures. We screened over 300 compounds for their ability to (1) support growth in low iron medium of a Pseudomonas aeruginosa siderophore biosynthesis deletion mutant, or (2) compete with a bactericidal siderophore-antibiotic conjugate for siderophore receptor access. From these assays we identified a set of small molecules that fulfilled one or both of these criteria. We then synthesized these compounds with functional groups suitable for attachment to both monobactam and cephalosporin core structures. Siderophore-beta-lactam conjugates then were tested against a panel of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains. Although several of the resultant chimeric compounds had antimicrobial activity approaching that of ceftazidime, and most compounds demonstrated very potent activity against their cellular targets, only a single compound was obtained that had enhanced, siderophore-mediated antibacterial activity. Results with tonB mutants frequently showed increased rather than decreased susceptibilities. suggesting that multiple factors influenced the intracellular concentration of the drugs.

Polycyclic aromatic hydrocarbons in food products originating from locally reared animals in Kuwait.

Analysis for the presence of 12 polycyclic aromatic hydrocarbons (PAHs) in 327 foodstuff samples originating from locally reared animals was carried out. The data revealed that non-carcinogenic PAHs were detected in considerable amounts in several food commodities. The carcinogenic PAH concentrations were relatively low in most of the samples investigated. Among the carcinogenic PAHs detected, chrysene had the highest concentration.

Rapid and simple method for determination of cholesterol in processed food.

An improved method for determination of cholesterol in processed food with only one extraction and without solvent removal was developed. Total time to analyze a sample including gas chromatographic (GC) analysis is 45 min. Food samples spiked with internal standard are hydrolyzed in a screw-capped vial with saturated methanolic KOH. Cyclohexane is added to the mixture, and the upper layer is analyzed by GC on a capillary column. Average recoveries of spiked white eggs are 99 +/- 0.5%. Fifteen types of processed food containing shrimp, fish, meat, cheese, eggs, and vegetables were analyzed with this method and with the AOAC method.