Steroid derivatives as potential antimicrobial agents against Staphylococcus aureus planktonic cells

In this work, the antibacterial activity of deflazacort and several of its synthetic precursors was tested against a panel of bacterial pathogens responsible for most drug-resistant infections including Staphylococcus aureus, Enterococcus spp., Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. The derivative of deflazacort, PYED-1 (pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1) showed the best antibacterial activity in a dose-dependent way. We focused on the action of PYED-1 against S. aureus cells. PYED-1 exhibited an additive antimicrobial effect with gentamicin and oxacillin against the methicillin-resistant S. aureus isolate 00717. In addition to its antimicrobial effect, PYED-1 was found to repress the expression of several virulence factors of S. aureus, including toxins encoded by the hla (alpha-haemolysin), hlb (beta-haemolysin), lukE-D (leucotoxins E-D), and sea (staphylococcal enterotoxin A) genes, and cell surface factors (fnbB (fibronectin-binding protein B) and capC (capsule biosynthesis protein C)). The expression levels of autolysin isaA (immunodominant staphylococcal antigen) were also increased

The glucocorticoid PYED-1 disrupts mature biofilms of Candida spp. and inhibits hyphal development in Candida albicans

Invasive Candida infections have become a global public health problem due to the increase of Candida species resistant against antifungal therapeutics. The glucocorticoid PYED-1 (pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1) has antimicrobial activity against various bacterial taxa. Consequently, it might be considered for the treatment of Candida infections. The antifungal activity of PYED-1 was evaluated against several fungal strains that were representative of the five species that causes the majority of Candida infections—namely, Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis and Candida krusei. PYED-1 exhibited a weak antifungal activity and a fungistatic effect on all five Candida species. On the other hand, PYED-1 exhibited a good antibiofilm activity, and was able to eradicate the preformed biofilms of all Candida species analyzed. Moreover, PYED-1 inhibited germ tube and hyphae formation of C. albicans and reduced adhesion of C. albicans to abiotic surfaces by up to 30%

N-nonyloxypentyl-l-deoxynojirimycin inhibits growth, biofilm formation and virulence factors expression of Staphylococcus aureus

Staphylococcus aureus is one of the major causes of hospital-and community-associated bacterial infections throughout the world, which are difficult to treat due to the rising number of drug-resistant strains. New molecules displaying potent activity against this bacterium are urgently needed. In this study, d-and l-deoxynojirimycin (DNJ) and a small library of their N-alkyl derivatives were screened against S. aureus ATCC 29213, with the aim to identify novel candidates with inhibitory potential. Among them, N-nonyloxypentyl-l-DNJ (l-NPDNJ) proved to be the most active compound against S. aureus ATCC 29213 and its clinical isolates, with the minimum inhibitory concentration (MIC) value of 128 µg/mL. l-NPDNJ also displayed an additive effect with gentamicin and oxacillin against the gentamicin-and methicillin-resistant S. aureus isolate 00717. Sub-MIC values of l-NPDNJ affected S. aureus biofilm development in a dose-dependent manner, inducing a strong reduction in biofilm biomass. Moreover, real-time reverse transcriptase PCR analysis revealed that l-NPDNJ effectively inhibited at sub-MIC values the transcription of the spa, hla, hlb and sea virulence genes, as well as the agrA and saeR response regulator genes

Regulation of mGlu4 metabotropic glutamate receptor signaling by type-2 G-protein coupled receptor kinase (GRK2

ABSTRACT We examined the role of G-protein coupled receptor kinase-2 (GRK2) in the homologous desensitization of mGlu4 metabotropic glutamate receptors transiently expressed in human embryonic kidney (HEK) 293 cells. Receptor activation with the agonist L-2-amino-4-phosphonobutanoate (L-AP4) stimulated at least two distinct signaling pathways: inhibition of cAMP formation and activation of the mitogen-activated protein kinase (MAPK) pathway [assessed by Western blot analysis of phosphorylated extracellular signal-regulated kinase (ERK) 1 and 2]. Activation of both pathways was attenuated by pertussis toxin. Overexpression of GRK2 (but not GRK4) largely attenuated the stimulation of the MAPK pathway by L-AP4, whereas it slightly potentiated the inhibition of FSK-stimulated cAMP formation. Transfection with a kinase-dead mutant of GRK2 (GRK2-K220R) or with the C-terminal fragment of GRK2 also reduced the mGlu4-mediated stimulation of MAPK, suggesting that GRK2 binds to the G␤␥ subunits to inhibit signal propagation toward the MAPK pathway. This was confirmed by the evidence that GRK2 coimmunoprecipitated with G␤␥ subunits in an agonist-dependent manner. Finally, neither GRK2 nor its kinase-dead mutant had any effect on agonist-induced mGlu4 receptor internalization in HEK293 cells transiently transfected with GFP-tagged receptors. Agonist-dependent internalization was instead abolished by a negative-dominant mutant of dynamin, which also reduced the stimulation of MAPK pathway by L-AP4. We speculate that GRK2 acts as a "switch molecule" by inhibiting the mGlu4 receptor-mediated stimulation of MAPK and therefore directing the signal propagation toward the inhibition of adenylyl cyclase. Metabotropic glutamate (mGlu) receptors, which belong to the third class of the G protein-coupled receptor (GPCR) superfamily, modulate excitatory synaptic transmission and are implicated in different aspects of central nervous system physiology, including motor control, motor coordination, sensory perception and pain transmission, learning and memory processes, and developmental plasticity Homologous desensitization of GCPRs is mediated by a family of enzymes called G-protein coupled receptor kinases (GRKs). This family includes GRK1, which corresponds to rhodopsin kinase, GRK2, and -3, which are ubiquitous and are activated by G-protein ␤␥ subunits, and GRK4, -5, and -6

2d and 3d palmprint extraction by an automated ultrasound system

In this work, some possible procedures to extract both 2D and 3D palmprints fromthe same experimental 3D ultrasound image of the human palmare presented. The ultrasound system used to achieve the 3D images is composed of a CNC commercial pantograph, which moves a high frequency (12 MHz) ultrasound probe along its elevation direction to cover the desired area of the human palm. The ULtrasound Advanced Open Platform (ULA-OP) is employed as ultrasound imaging system

Palmprint Recognition Through a Reliable Ultrasound Acquisition System and a 3D Template

Biometric systems based on ultrasonic images have the merits of being very resistent to spoof attacks. In this work, a 3D recognition procedure based on palmprint ultrasound images acquired through a reliable system, which uses a gel pad as coupling medium between the ultrasound probe and the hand, is proposed and experimentally evaluated. Several 2D palmprint images, at different under-skin depths, are extracted from the acquired volumetric image. For each of them a template is generated through an original procedure. The various templates are then opportunely combined to obtain a 3D template

3D Finite Element Analysis of the Langevin Transducer

In this paper, a 3-D finite element analysis of the vibrational behaviour of the Langevin transducer and of the dependence of its performances on the length to diameter ratio is presented. Several transducers with total length greater than, comparable to, and smaller than the diameter have been simulated, and the frequency spectrum is drawn in order to identify the regions where coupling between thickness and radial modes exists, and to highlight the limit of the classical 1-D theory. Performances of transducers with any length to diameter ratio, but all working at the same frequency (153 kHz), are evaluated by comparing the product between the output mean displacement and the area of the radiating surface. Results have shown that Langevin transducers with comparable longitudinal and lateral dimensions have performances comparable to or even better than transducers with total length much greater than diameter