Abstract:Pathogenic bacteria are one of the major concerns in food industries and water treatment facilities because of their rapid growth and deleterious effects on human health. The development of fast and accurate detection and identification systems for bacterial strains has long been an important issue to researchers. Although confirmative for the identification of bacteria, conventional methods require time-consuming process involving either the test of characteristic metabolites or cellular reproductive cycles. … Show more
“…(2) Fortunately, major advancements in bacterial pathogen detection using siderophore-based sensors are in development by several groups and will certainly play an important role in the future for progressing sideromycin antibiotics into the clinic. (58–59)…”
Siderophores are multidentate iron(III) chelators used by bacteria for iron assimilation. Sideromycins, also called siderophore-antibiotic conjugates, are a unique subset of siderophores that enter bacterial cells via siderophore uptake pathways and deliver the toxic antibiotic in a ‘Trojan Horse’ fashion. Sideromycins represent a novel antibiotic delivery technology with untapped potential for developing sophisticated microbe-selective antibacterial agents that limit the emergence of bacterial resistance. The chemical synthesis of a series of mono-, bis-, and trihydroxamate sideromycins are described here along with their biological evaluation in antibacterial susceptibility assays. The linear hydroxamate siderophores used for the sideromycins in this study were derived from the ferrioxamine family and inspired by the naturally occurring salmycin sideromycins. The antibacterial agents used were a β-lactam carbacepholosporin, Lorabid®, and a fluoroquinolone, ciprofloxacin, chosen for the different locations of their biological targets, the periplasm (extracellular) and the cytoplasm (intracellular). The linear hydroxamate-based sideromycins were selectively toxic towards Gram-positive bacteria, especially Staphylococcus aureus SG511 (MIC = 1.0 µM for the trihydroxamate-fluoroquinolone sideromycin). Siderophore-sideromycin competition assays demonstrated that only the fluoroquinolone sideromycins required membrane transport to reach their cytoplasmic biological target and that a trihydroxamate siderophore backbone was required for protein-mediated active transport of the sideromycins into S. aureus cells via siderophore uptake pathways. This work represents a comprehensive study of linear hydroxamate sideromycins and teaches how to build effective hydroxamate-based sideromycins as Gram-positive selective antibiotic agents.
“…(2) Fortunately, major advancements in bacterial pathogen detection using siderophore-based sensors are in development by several groups and will certainly play an important role in the future for progressing sideromycin antibiotics into the clinic. (58–59)…”
Siderophores are multidentate iron(III) chelators used by bacteria for iron assimilation. Sideromycins, also called siderophore-antibiotic conjugates, are a unique subset of siderophores that enter bacterial cells via siderophore uptake pathways and deliver the toxic antibiotic in a ‘Trojan Horse’ fashion. Sideromycins represent a novel antibiotic delivery technology with untapped potential for developing sophisticated microbe-selective antibacterial agents that limit the emergence of bacterial resistance. The chemical synthesis of a series of mono-, bis-, and trihydroxamate sideromycins are described here along with their biological evaluation in antibacterial susceptibility assays. The linear hydroxamate siderophores used for the sideromycins in this study were derived from the ferrioxamine family and inspired by the naturally occurring salmycin sideromycins. The antibacterial agents used were a β-lactam carbacepholosporin, Lorabid®, and a fluoroquinolone, ciprofloxacin, chosen for the different locations of their biological targets, the periplasm (extracellular) and the cytoplasm (intracellular). The linear hydroxamate-based sideromycins were selectively toxic towards Gram-positive bacteria, especially Staphylococcus aureus SG511 (MIC = 1.0 µM for the trihydroxamate-fluoroquinolone sideromycin). Siderophore-sideromycin competition assays demonstrated that only the fluoroquinolone sideromycins required membrane transport to reach their cytoplasmic biological target and that a trihydroxamate siderophore backbone was required for protein-mediated active transport of the sideromycins into S. aureus cells via siderophore uptake pathways. This work represents a comprehensive study of linear hydroxamate sideromycins and teaches how to build effective hydroxamate-based sideromycins as Gram-positive selective antibiotic agents.
“…Several authors have reviewed the advantages of nanomaterialbased pathogen sensing in detail [393][394][395]. Nanomaterial-based microbial sensors generally utilize the same strategy, but because they possess unique optical and electrical properties in combination with spacious, easily functionalized surfaces, nanomaterials offer significant improvements in selectivity, speed and sensitivity compared to chemical or biological methods based on macroscale materials.…”
In this article, several applications of nanomaterials in food packaging and food safety are reviewed, including: polymer/clay nanocomposites as high barrier packaging materials, silver nanoparticles as potent antimicrobial agents, and nanosensors and nanomaterial-based assays for the detection of food-relevant analytes (gasses, small organic molecules and food-borne pathogens). In addition to covering the technical aspects of these topics, the current commercial status and understanding of health implications of these technologies are also discussed. These applications were chosen because they do not involve direct addition of nanoparticles to consumed foods, and thus are more likely to be marketed to the public in the short term.
“…These results demonstrate that using the tube as a concentration device detection can be achieved in a few hours vs. industry standard methods that require a minimum 18–24 hour of enrichment for detection as described in the BAM protocols. While, clogging has been a problem in microfluidic devices used for blood and food applications 23–25 , clogging was not observed when a 1 mm diameter tube was used in these studies in blood and food matrices (Tube concentration, detachment and detection of S. typhimurium from food matrix using lateral flow immunoassays is discussed in the supplement, S3 . ).Figure 7Tube capturing in a real food matrices; ( a ) Experiment set-up for capturing in ground chicken.…”
A simple technique that employs an antibody coated polydimethylsiloxane tube is used for effective capturing of bloodborne and foodborne pathogens. By recirculating the entire sample through the antibody coated tube, accumulation of target pathogens is achieved, thereby delivering a higher concentration of pathogens in a small volume. The described method can provide an effective and economical solution to microbiology techniques that rely on enrichment, thereby expediting diagnostics. Using this method 80.3 ± 5.6% of Staphylococcus aureus with a starting concentration of ~107 CFU/mL and 95.4 ± 1.0% of Methicillin-resistant Staphylococcus aureus with starting concentration of ~104 CFU/mL were removed from 5 mL blood in a few hours. This concept was extended to live rats with an induced bloodstream S. aureus infection. A reduction of two orders of magnitude in the bacterial load of the rats was observed within a few hours. The same technique was used to capture a food pathogen, Salmonella typhimurium, with starting concentrations as low as ~100 CFU, from 100 or 250 mL of culture broth within similar timeframes as above. The feasibility for food pathogen testing applications was additionally confirmed by capturing and detecting S. typhimurium in ground chicken and ground beef.
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