The emerging threat of drug resistant bacteria has prompted the investigation into bacterial signaling pathways responsible for pathogenesis. One such mechanism by which bacteria regulate their physiology during infection of a host is through a process known as quorum sensing (QS). Bacteria use QS to regulate community-wide gene expression in response to changes in population density. In order to sense these changes in population density, bacteria produce, secrete and detect small molecules called autoinducers. The most common signals detected by Gram-negative and Gram-positive bacteria are acylated homoserine lactones and autoinducing peptides (AIPs), respectively. However, increasing evidence has supported a role for the small molecule nitric oxide (NO) in influencing QS-mediated group behaviors like bioluminescence, biofilm production, and virulence. In this review, we discuss three bacteria that have an established role for NO in influencing bacterial physiology through QS circuits. In two Vibrio species, NO has been shown to affect QS pathways upon coordination of hemoprotein sensors. Further, NO has been demonstrated to serve a protective role against staphylococcal pneumonia through S-nitrosylation of a QS regulator of virulence.
We have studied the catalytic carbon monoxide (CO) oxidation (CO+0.5O 2 → CO 2) reaction using a powder catalyst composed of both copper (5wt% loading) and titania (CuO x-TiO 2). Our study was focused on revealing the role of Cu, and the interaction between Cu and TiO 2 , by systematic comparison between two nanocatalysts, CuO x-TiO 2 and pure CuO x. We interrogated these catal ysts under in situ conditions using X-ray Diffraction (XRD), X-ray Absorption Fine Structure (XAFS) and Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) to probe the structure and electronic properties of the catalyst at all stages of the reaction and simultaneously probe the surface states or intermediates of this reaction. With the aid of several ex situ characterization techniques including Transmission Electron Microscopy (TEM), the local catalyst morphology and structure was also studied. Our results show that a CuO x-TiO 2 system is more active than bulk CuO x for the CO oxidation reaction due to its lower onset temperature and better stability at higher temperatures. Our results also suggests that a surface Cu + species observed in the CuO x-TiO 2 interface are likely to be a key player in the CO oxidation mechanism, while implicating that the stabilization of this species is probably associated with the oxide-oxide interface. Both in situ DRIFTS and XAFS measurements reveal that there is likely to be a Cu(Ti)-O mixed oxide at this interface. We discuss the nature of this Cu(Ti)-O interface and interpret its role on the CO oxidation reaction.
Neuroaxonal damage is a feature of various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Phosphorylated neurofilament heavy chain (pNfH) is a cytoskeletal structural protein released as a result of axonal damage into the CSF, and subsequently into the blood. Due to high specificity for neuronal cell damage, pNfH is advantageous over other biomarkers, for ALS disease identification. Here, we review the structure and function of neurofilaments and their role in detection of various neurodegenerative conditions. Additionally, a retrospective meta-analysis was performed to depict the significance of pNfH as a valuable diagnostic and prognostic biomarker in ALS.
Dermatomycosis of the hair, skin or nails are one of the most common fungal infections worldwide. Beyond permanent damage to the affected area, the risk of severe dermatomycosis in immunocompromised people can be life-threatening. The potential risk of delayed or improper treatment highlights the need for a rapid and accurate diagnosis. However, with traditional methods of fungal diagnostics such as culture, a diagnosis can take several weeks. Alternative diagnostic technologies have been developed which allow for an appropriate and timely selection of an antifungal treatment, preventing nonspecific over-the-counter self-medication. Such techniques include molecular methods such as PCR, real-time PCR, DNA microarray, next-generation sequencing, in addition to matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry. Molecular methods can help close the “diagnostic gap” observed with traditional cultures and microscopy and allow for a rapid detection of dermatomycosis with increased sensitivity and specificity. In this review, advantages and disadvantages of traditional and molecular techniques are discussed, in addition to the importance of species-specific dermatophyte determination. Finally, we highlight the need for clinicians to adapt molecular techniques for the rapid and reliable detection of dermatomycosis infections and to reduce adverse events. Lay Abstract Dermatomycosis is one of the most common fungal infections worldwide. Traditional fungal diagnostics are limited and can take several weeks. Molecular techniques can detect dermatomycosis pathogens quickly and allow for species-specific identification which is important for treatment.
Biofilm formation on the surfaces of indwelling medical devices has become a growing health threat due to the development of antimicrobial resistance to infection-causing bacteria. For example, ventilator-associated pneumonia caused by Pseudomonas and Staphylococci species has become a significant concern in treatment of patients during COVID-19 pandemic. Nanostructured surfaces with antifouling activity are of interest as a promising strategy to prevent bacterial adhesion without triggering drug resistance. In this study, we report a facile evaporative approach to prepare block copolymer film coatings with nanoscale topography that resist bacterial adhesion. The initial attachment of the target bacterium Pseudomonas aeruginosa PAO1 to copolymer films as well as homopolymer films was evaluated by fluorescence microscopy. Significant reduction in bacterial adhesion (93–99% less) and area coverage (>92% less) on the copolymer films was observed compared with that on the control and homopolymer films [poly(methacrylic acid) (PMAA)only 40 and 23% less, respectively]. The surfaces of poly(styrene)-PMAA copolymer films with patterned nanoscale topography that contains sharp peaks ranging from 20 to 80 nm spaced at 30–50 nm were confirmed by atomic force microscopy and the corresponding surface morphology analysis. Investigation of the surface wettability and surface potential of polymer films assists in understanding the effect of surface properties on the bacterial attachment. Comparison of bacterial growth studies in polymer solutions with the growth studies on coatings highlights the importance of physical nanostructure in resisting bacterial adhesion, as opposed to chemical characteristics of the copolymers. Such self-patterned antifouling surface coatings, produced with a straightforward and energy-efficient approach, could provide a convenient and effective method to resist bacterial fouling on the surface of medical devices and reduce device-associated infections.
Nitric oxide (NO) detection and signalling are widely mediated by haemoproteins in eukaryotes and bacteria. This review highlights the ligand-binding properties, activation mechanisms, and structures of six proteins that have been classified as haem-based NO-sensing proteins: sGC, H-NOX, YybT, E75, NosP, and DNR. sGC is a eukaryotic haem-based sensor that responds to NO to catalyse the production of the ubiquitous secondary messaging signalling molecule cGMP. Much of the progress toward elucidating the NO activation mechanism of sGC has been achieved through the study of bacterial haem-nitric oxide and oxygen (H-NOX) binding proteins. H-NOX proteins are capable of influencing downstream signal transduction in several bacterial species; however, many bacteria that respond to nanomolar concentrations of NO do not contain an annotated H-NOX domain. Of all bacterial species, NO signalling has been most frequently investigated in Pseudomonas aeruginosa, which do not encode an H-NOX domain, and so several receptors of NO have been suggested in this species. Most recently, a newly discovered family of NO-sensing proteins (NosP) was demonstrated to be a mediator of a histidine kinase signal-transduction pathway in P. aeruginosa. NosP proteins are widely conserved in bacteria but have thus far only been characterized in P. aeruginosa. Additionally, a transcriptional regulator called DNR (dissimilative nitrate respiration regulator) has been shown to be a haem-based NO receptor that controls anaerobic denitrification in P. aeruginosa. Another putative bacterial haem-based NO sensor, the cyclic-di-AMP-specific phosphodiesterase YybT is widely distributed across the firmicutes phylum and has been implicated in bacterial survival. Finally, a putative NO sensor in insects, E75, is a haem-based transcriptional regulator. sGC, H-NOX, YybT, E75, NosP, and DNR are discussed in more detail.
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