273 research outputs found
Regulatory potential of post-translational modifications in bacteria
No full textNo abstract availabl
Evolutionary age of genes can assist in genome mining
No full textThe rate of sequencing microbial genomes is accelerating, with the hope of discovering new antibiotics, cures for various diseases or new industrial enzymes. However, about 25-30% of the genes in the sequenced microbial genomes do not have an assigned function. Predicting the functions of these “unknown” genes could unlock a considerable biological potential for biomedical and biotechnology applications, as well as further our understanding of the molecular tenets of life. Current methods for gene mining rely basically on comparison of primary sequences or 3D-structures to those of already characterized genes. The problem with such approaches is that unknown genes with no homology to the already characterized genes remain completely out of reach. Herein, I argue that evolutionary approaches, such as the genomic phylostratigraphy, can make a substantial contribution to genome mining – especially regarding genes with no homology to the characterized ones. My group has recently used genomic phylostratigraphy to discover new genes involved in sporulation of the bacterial model organism Bacillus subtilis. These new sporulation genes exhibited no sequence homology with the known sporulation genes and were missed by all other genome mining approaches. They have been discovered solely based on their evolutionary age. Along these lines, I argue that phylostratigraphy should be integrated into genome mining pipelines and develop a brief example of how this could be done
Boron nitride nanomaterials: Biocompatibility and bio-applications
No full textBoron nitride has structural characteristics similar to carbon 2D materials (graphene and its derivatives) and its layered structure has been exploited to form different nanostructures such as nanohorns, nanotubes, nanoparticles and nanosheets. Unlike graphene and other carbon based 2D materials, boron nitride has a higher chemical stability. Owing to these properties, boron nitride has been used in different applications as a filler, lubricant and as a protective coating. Boron nitride has also been applied in the biomedical field to some extent, but far less than other 2D carbon materials. This review explores the potential of boron nitride for biomedical applications where the focus is on boron nitride biocompatibility in vivo and in vitro, its applicability as a coating material/composite and its anti-bacterial properties. Geometry, material processing and the type of biological analysis appear to be relevant parameters in assessing boron nitride bio-compatibility. Engineering of both these variables and the coating would open the door for some applications in the medical field for boron nitride, such as drug delivery, imaging and cell stimulation
Silver Nanoparticles: Bactericidal and Mechanistic Approach against Drug Resistant Pathogens
No full textThis review highlights the different modes of synthesizing silver nanoparticles (AgNPs) from their elemental state to particle format and their mechanism of action against multidrug-resistant and biofilm-forming bacterial pathogens. Various studies have demonstrated that the AgNPs cause oxidative stress, protein dysfunction, membrane disruption, and DNA damage in bacteria, ultimately leading to bacterial death. AgNPs have also been found to alter the adhesion of bacterial cells to prevent biofilm formation. The benefits of using AgNPs in medicine are, to some extent, counter-weighted by their toxic effect on humans and the environment. In this review, we have compiled recent studies demonstrating the antibacterial activity of AgNPs, and we are discussing the known mechanisms of action of AgNPs against bacterial pathogens. Ongoing clinical trials involving AgNPs are briefly presented. A particular focus is placed on the mechanism of interaction of AgNPs with bacterial biofilms, which are a significant pathogenicity determinant. A brief overview of the use of AgNPs in other medical applications (e.g., diagnostics, promotion of wound healing) and the non-medical sectors is presented. Finally, current drawbacks and limitations of AgNPs use in medicine are discussed, and perspectives for the improved future use of functionalized AgNPs in medical applications are presented
Protein phosphorylation in bcterial signaling and regulation
No full textIn 2003, it was demonstrated for the first time that bacteria possess protein-tyrosine kinases (BY-kinases), capable of phosphorylating other cellular proteins and regulating their activity. It soon became apparent that these kinases phosphorylate a number of protein substrates, involved in different cellular processes. More recently, we found out that BY-kinases can be activated by several distinct protein interactants, and are capable of engaging in cross-phosphorylation with other kinases. Evolutionary studies based on genome comparison indicate that BY-kinases exist only in bacteria. They are non-essential (present in about 40% bacterial genomes), and their knockouts lead to pleiotropic phenotypes, since they phosphorylate many substrates. Surprisingly, BY-kinase genes accumulate mutations at an increased rate (non-synonymous substitution rate significantly higher than other bacterial genes). One direct consequence of this phenomenon is no detectable co-evolution between kinases and their substrates. Their promiscuity towards substrates thus seems to be “hard-wired”, but why would bacteria maintain such promiscuous regulatory devices? One explanation is the maintenance of BY-kinases as rapidly evolving regulators, which can readily adopt new substrates when environmental changes impose selective pressure for quick evolution of new regulatory modules. Their role is clearly not to act as master regulators, dedicated to triggering a single response, but they might rather be employed to contribute to fine-tuning and improving robustness of various cellular responses. This unique feature makes BY-kinases a potentially useful tool in synthetic biology. While other bacterial kinases are very specific and their signaling pathways insulated, BY-kinase can relatively easily be engineered to adopt new substrates and control new biosynthetic processes. Since they are absent in humans, and regulate some key functions in pathogenic bacteria, they are also very promising targets for new antibacterial drugs
P-Ser-HPr-a link between carbon metabolism and the virulence of some pathogenic bacteria
No full textHPr kinase/phosphorylase phosphorylates HPr, a phosphocarrier protein of the phosphoenolpyruvate:carbohydrate phosphotransferase system, at serine-46. P-Ser-HPr is the central regulator of carbon metabolism in Gram-positive bacteria, but also plays a role in virulence development of certain pathogens. In Listeria monocytogenes, several virulence genes, which depend on the transcription activator PrfA, are repressed by glucose, fructose, etc., in a catabolite repressor (CcpA)-independent mechanism. However, the catabolite co-repressor P-Ser-HPr was found to inhibit the activity of PrfA. In an hprKV267F mutant, in which most of the HPr is transformed into P-Ser-HPr, PrfA was barely active. The ptsH1 mutation (Ser-46 of HPr replaced with an alanine) prevented the inhibitory effect of the hprKV267F mutation. Interestingly, disruption of ccpA also inhibited PrfA activity. This effect is probably also mediated via P-Ser-HPr, since ccpA disruption leads to elevated amounts of P-Ser-HPr. Indeed, a ccpA ptsH1 double mutant exhibited normal PrfA activity. In S. pyogenes, the expression of several virulence genes depends on the transcription activator Mga. Interestingly, the mga promoter is preceded by an operator site, which serves as target for the CcpA/P-Ser-HPr complex. Numerous Gram-negative pathogens also contain hprK, which is often organised in an operon with transcription regulators necessary for the development of virulence, indicating that in these organisms P-Ser-HPr also plays a role in pathogenesis. Indeed, inactivation of Neisseria meningitidis hprK strongly diminished cell adhesion of this pathogen
Impact of phosphoproteomics on studies of bacterial physiology
No full textProtein phosphorylation on serine, threonine and tyrosine is recognized as a major tool of signal transduction in bacteria. However, progress in the field has been hampered by the lack of global and site-specific data on bacterial phosphoproteomes. Recent advances in mass spectrometrybased proteomics have encouraged bacteriologists to start using powerful gel-free approaches for global detection of phosphorylated proteins. These studies have generated large data sets of proteins phosphorylated on serine, threonine and tyrosine, with identified phosphorylation sites which represent an excellent starting point for in-depth physiological characterization of kinases and their substrates. The list of phosphorylated proteins inspired a number of physiological studies in which the identity of the phosphorylation site facilitated the elucidation of molecular mechanisms of signaling and regulation. Bacterial phosphoproteomics also provided interesting insights into the evolutionary aspects of protein phosphorylation. The field is rapidly embracing quantitative mass spectrometry strategies, comparing phosphoproteome dynamics in changing conditions and aiming to reconstruct the entire regulatory networks by linking kinases to their physiological substrates
Strong Antimicrobial Activity of Silver Nanoparticles Obtained by the Green Synthesis in Viridibacillus sp. Extracts
No full textRecently, green silver nanoparticles (G-AgNPs) have gained much attention in medical science due to their extraordinary effects against multidrug-resistant microorganisms. The strong antimicrobial nature of G-AgNPs corresponds to their unique physicochemical properties such as size, shape, surface charge, and active surface groups available to interact with the pathogens. The current study demonstrates a simple, environmentally friendly, and economical method to produce G-AgNPs from an environmental isolate of Viridibacillus sp. The produced G-AgNPs were characterized by various analytical methods, including UV-Vis spectroscopy, single-particle inductively coupled plasma-mass spectrometry (sp-ICP-MS), scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy (EDX), elemental mapping, transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and Thermogravimetric analysis (TGA). The reduction of Ag+ to Ag\ub0 was observed by UV-Vis spectroscopy, which demonstrated the formation of stable G-AgNPs with a Surface Plasmon Resonance (SPR) band at the maximum of 430 nm. TEM analysis demonstrated that the G-AgNPs were spherical with a 5–30 nm size range. The produced G-AgNPs were stable for more than 1 year in an aqueous solution at 4\ub0C. Importantly, G-AgNPs showed remarkable antimicrobial activity against Gram-negative pathogens- E. coli and P. aeruginosa with MIC values of 0.1 and 4 μg/mL and MBC values of 1 and 8 μg/mL, respectively. This level of antimicrobial activity is superior to other AgNPs reported in the literature
Rowan Berries: A Potential Source for Green Synthesis of Extremely Monodisperse Gold and Silver Nanoparticles and Their Antimicrobial Property
No full textRowanberries (Sorbus aucuparia) are omnipresent in Europe. The medicinal importance of rowanberries is widely known and corresponds to the active ingredients present in the fruits, mainly polyphenols, carotenoids, and organic acids. In the current study, we explored rowanberries for the reduction of gold and silver salts into nanoparticles. Rowanberries-mediated gold nanoparticles (RB-AuNPs) formed within 5 s at room temperature, and silver nanoparticles (RB-AgNPs) formed in 20 min at 90 °C. The produced nanoparticles were thoroughly characterized by UV-Vis spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray (EDX), transmission electron microscopy (TEM), dynamic light scattering (DLS), single-particle inductively coupled plasma–mass spectrometry (sp-ICP-MS), thermogravimetric analysis (TGA), Fourier transform-infrared spectroscopy (FT-IR) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF). The characterization confirmed that the nanoparticles are highly monodisperse, spherical, stable over long periods, and exhibit a high negative zeta potential values. The produced RB-AuNPs and RB-AgNPs were 90–100 nm and 20–30 nm in size with a thick biological corona layer surrounding them, providing extreme stability but lowering the antimicrobial activity. The antimicrobials study of RB-AgNPs revealed that the nanoparticles have antimicrobial potential with an MBC value of 100 µg/mL against P. aeruginosa and 200 µg/mL against E. coli
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