Gramicidin D enhances the antibacterial activity of fluoride.
Ontology highlight
ABSTRACT:
SUBMITTER: Nelson JW
PROVIDER: S-EPMC4048840 | biostudies-literature | 2014 Jul
REPOSITORIES: biostudies-literature
Publications
Gramicidin D enhances the antibacterial activity of fluoride.
Nelson James W JW Zhou Zhiyuan Z Breaker Ronald R RR
Bioorganic & medicinal chemistry letters 20140328 13
Fluoride is a toxic anion found in many natural environments. One of the major bacterial defenses against fluoride is the cell envelope, which limits passage of the membrane-impermeant fluoride anion. Accordingly, compounds that enhance the permeability of bacterial membranes to fluoride should also enhance fluoride toxicity. In this study, we demonstrate that the pore-forming antibiotic gramicidin D increases fluoride uptake in Bacillus subtilis and that the antibacterial activity of this compo ...[more]
Similar Datasets
Project description:Fluoride has long been known to inhibit bacterial and fungal cell growth most likely by blocking the functions of key metabolic enzymes. In this study, we demonstrate that antifungal compounds that disrupt cell membrane integrity exhibit improved ability to inhibit cell growth when used with millimolar concentrations of fluoride. Specifically, antifungal compounds of the polyene class and an antifungal peptide exhibit synergy with fluoride to inhibit the growth of various fungal species, including Candida albicans. Our results demonstrate that certain compounds can be found that increase the cellular uptake of fluoride, and provide new opportunities for creating antimicrobial compounds whose functions are enhanced when combined with otherwise sub-inhibitory concentrations of small ions.
| S-EPMC4498161 | biostudies-literature
Project description:BackgroundIt is generally accepted that antibacterial properties of Ag nanoparticles (AgNPs) are dictated by their dissolved fraction. However, dissolution-based concept alone does not fully explain the toxic potency of nanoparticulate silver compared to silver ions.Methodology/principal findingsHerein, we demonstrated that the direct contact between bacterial cell and AgNPs' surface enhanced the toxicity of nanosilver. More specifically, cell-NP contact increased the cellular uptake of particle-associated Ag ions - the single and ultimate cause of toxicity. To prove that, we evaluated the toxicity of three different AgNPs (uncoated, PVP-coated and protein-coated) to six bacterial strains: Gram-negative Escherichia coli, Pseudomonas fluorescens, P. putida and P. aeruginosa and Gram-positive Bacillus subtilis and Staphylococcus aureus. While the toxicity of AgNO3 to these bacteria varied only slightly (the 4-h EC50 ranged from 0.3 to 1.2 mg Ag/l), the 4-h EC50 values of protein-coated AgNPs for various bacterial strains differed remarkably, from 0.35 to 46 mg Ag/l. By systematically comparing the intracellular and extracellular free Ag(+) liberated from AgNPs, we demonstrated that not only extracellular dissolution in the bacterial test environment but also additional dissolution taking place at the particle-cell interface played an essential role in antibacterial action of AgNPs. The role of the NP-cell contact in dictating the antibacterial activity of Ag-NPs was additionally proven by the following observations: (i) separation of bacterial cells from AgNPs by particle-impermeable membrane (cut-off 20 kDa, ?4 nm) significantly reduced the toxicity of AgNPs and (ii) P. aeruginosa cells which tended to attach onto AgNPs, exhibited the highest sensitivity to all forms of nanoparticulate Ag.Conclusions/significanceOur findings provide new insights into the mode of antibacterial action of nanosilver and explain some discrepancies in this field, showing that "Ag-ion" and "particle-specific" mechanisms are not controversial but, rather, are two faces of the same coin.
| S-EPMC3667828 | biostudies-literature
Project description:Antibiotic resistance has prompted the search for new agents that can inhibit bacterial growth. Moreover, colonization of abiotic surfaces by microorganisms and the formation of biofilms is a major cause of infections associated with medical implants, resulting in prolonged hospitalization periods and patient mortality. In this study we describe a water-based synthesis of yttrium fluoride (YF(3)) nanoparticles (NPs) using sonochemistry. The sonochemical irradiation of an aqueous solution of yttrium (III) acetate tetrahydrate [Y(Ac)(3) · (H(2)O)(4)], containing acidic HF as the fluorine ion source, yielded nanocrystalline needle-shaped YF(3) particles. The obtained NPs were characterized by scanning electron microscopy and X-ray elemental analysis. NP crystallinity was confirmed by electron and powder X-ray diffractions. YF(3) NPs showed antibacterial properties against two common bacterial pathogens (Escherichia coli and Staphylococcus aureus) at a ?g/mL range. We were also able to demonstrate that antimicrobial activity was dependent on NP size. In addition, catheters were surface modified with YF(3) NPs using a one-step synthesis and coating process. The coating procedure yielded a homogeneous YF(3) NP layer on the catheter, as analyzed by scanning electron microscopy and energy dispersive spectroscopy. These YF(3) NP-modified catheters were investigated for their ability to restrict bacterial biofilm formation. The YF(3) NP-coated catheters were able to significantly reduce bacterial colonization compared to the uncoated surface. Taken together, our results highlight the potential to further develop the concept of utilizing these metal fluoride NPs as novel antimicrobial and antibiofilm agents, taking advantage of their low solubility and providing extended protection.
| S-EPMC3496407 | biostudies-literature
Project description:Chloramphenicol (CAM) is a broad-spectrum antibiotic, limited to occasional only use in developed countries because of its potential toxicity. To explore the influence of polyamines on the uptake and activity of CAM into cells, a series of polyamine-CAM conjugates were synthesized. Both polyamine architecture and the position of CAM-scaffold substitution were crucial in augmenting the antibacterial and anticancer potency of the synthesized conjugates. Compounds 4 and 5, prepared by replacement of dichloro-acetyl group of CAM with succinic acid attached to N4 and N1 positions of N(8),N(8)-dibenzylspermidine, respectively, exhibited higher activity than CAM in inhibiting the puromycin reaction in a bacterial cell-free system. Kinetic and footprinting analysis revealed that whereas the CAM-scaffold preserved its role in competing with the binding of aminoacyl-tRNA 3'-terminus to ribosomal A-site, the polyamine-tail could interfere with the rotatory motion of aminoacyl-tRNA 3'-terminus toward the P-site. Compared to CAM, compounds 4 and 5 exhibited comparable or improved antibacterial activity, particularly against CAM-resistant strains. Compound 4 also possessed enhanced toxicity against human cancer cells, and lower toxicity against healthy human cells. Thus, the designed conjugates proved to be suitable tools in investigating the ribosomal catalytic center plasticity and some of them exhibited greater efficacy than CAM itself.
| S-EPMC4117768 | biostudies-literature
Project description:Periostitis, which is characterized by bony pain and diffuse periosteal ossification, has been increasingly reported with prolonged clinical use of voriconazole. While resolution of clinical symptoms following discontinuation of therapy suggests a causative role for voriconazole, the biological mechanisms contributing to voriconazole-induced periostitis are unknown. To elucidate potential mechanisms, we exposed human osteoblasts in vitro to voriconazole or fluconazole at 15 or 200 ?g/ml (reflecting systemic or local administration, respectively), under nonosteogenic or osteogenic conditions, for 1, 3, or 7 days and evaluated the effects on cell proliferation (reflected by total cellular DNA) and osteogenic differentiation (reflected by alkaline phosphatase activity, calcium accumulation, and expression of genes involved in osteogenic differentiation). Release of free fluoride, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) was also measured in cell supernatants of osteoblasts exposed to triazoles, with an ion-selective electrode (for free fluoride) and enzyme-linked immunosorbent assays (ELISAs) (for VEGF and PDGF). Voriconazole but not fluconazole significantly enhanced the proliferation and differentiation of osteoblasts. In contrast to clinical observations, no increases in free fluoride levels were detected following exposure to either voriconazole or fluconazole; however, significant increases in the expression of VEGF and PDGF by osteoblasts were observed following exposure to voriconazole. Our results demonstrate that voriconazole can induce osteoblast proliferation and enhance osteogenic activity in vitro. Importantly, and in contrast to the previously proposed mechanism of fluoride-stimulated osteogenesis, our findings suggest that voriconazole-induced periostitis may also occur through fluoride-independent mechanisms that enhance the expression of cytokines that can augment osteoblastic activity.
| S-EPMC4649155 | biostudies-literature
Project description:Phospholipases constitute a ubiquitous class of membrane-active enzymes that play a key role in cellular signaling, proliferation, and membrane trafficking. Aberrant phospholipase activity is implicated in a range of diseases including cancer, inflammation, and myocardial disease. Characterization of these enzymes is therefore important, both for improving the understanding of phospholipase catalysis and for accelerating pharmaceutical and biotechnological applications. This paper describes a novel approach to monitor, in situ and in real-time, the activity of phospholipase D (PLD) and phospholipase C (PLC) on planar lipid bilayers. This method is based on lipase-induced changes in the electrical charge of lipid bilayers and on the concomitant change in ion concentration near lipid membranes. The approach reports these changes in local ion concentration by a measurable change in the single channel ion conductance through pores of the ion channel-forming peptide gramicidin A. This enzyme assay takes advantage of the amplification characteristics of gramicidin pores to sense the activity of picomolar to nanomolar concentrations of membrane-active enzymes without requiring labeled substrates or products. The resulting method proceeds on lipid bilayers without the need for detergents, quantifies enzyme activity on native lipid substrates within minutes, and provides unique access to both leaflets of well-defined lipid bilayers; this method also makes it possible to generate planar lipid bilayers with transverse lipid asymmetry.
| S-EPMC2775016 | biostudies-literature
Project description:The design, synthesis, and characterization of enterobactin-antibiotic conjugates, hereafter Ent-Amp/Amx, where the ?-lactam antibiotics ampicillin (Amp) and amoxicillin (Amx) are linked to a monofunctionalized enterobactin scaffold via a stable poly(ethylene glycol) linker are reported. Under conditions of iron limitation, these siderophore-modified antibiotics provide enhanced antibacterial activity against Escherichia coli strains, including uropathogenic E. coli CFT073 and UTI89, enterohemorrhagic E. coli O157:H7, and enterotoxigenic E. coli O78:H11, compared to the parent ?-lactams. Studies with E. coli K-12 derivatives defective in ferric enterobactin transport reveal that the enhanced antibacterial activity observed for this strain requires the outer membrane ferric enterobactin transporter FepA. A remarkable 1000-fold decrease in minimum inhibitory concentration (MIC) value is observed for uropathogenic E. coli CFT073 relative to Amp/Amx, and time-kill kinetic studies demonstrate that Ent-Amp/Amx kill this strain more rapidly at 10-fold lower concentrations than the parent antibiotics. Moreover, Ent-Amp and Ent-Amx selectively kill E. coli CFT073 co-cultured with other bacterial species such as Staphylococcus aureus, and Ent-Amp exhibits low cytotoxicity against human T84 intestinal cells in both the apo and iron-bound forms. These studies demonstrate that the native enterobactin platform provides a means to effectively deliver antibacterial cargo across the outer membrane permeability barrier of Gram-negative pathogens utilizing enterobactin for iron acquisition.
| S-EPMC4353011 | biostudies-literature
Project description:Multifactorial antibacterial action is an important feature of honey; however, its bactericidal efficacy against biofilm-embedded bacteria is limited. The aim of this study was to investigate the impact of vitamin C (Vit C) on the antibacterial activity of natural honeys against planktonic as well as biofilm-embedded bacterial pathogens. The antibacterial activity of four honey samples supplemented with Vit C was expressed as the minimum inhibitory concentration (MIC). At sub-MICs, Vit C significantly increased the antibacterial activity of the tested honeys against Pseudomonas aeruginosa in planktonic cultures. However, after supplementation, honeydew honey, the most active honey, was ineffective against Staphylococcus aureus. On the other hand, when 100% honeydew honey was supplemented with Vit C (100 mg/g of honey) in a multispecies wound biofilm model, complete eradication of almost all bacterial isolates, including S. aureus, was observed. Furthermore, a mixture of honey and Vit C was partially effective against Enterococcus faecalis, whereas honey alone exhibited no antibacterial activity against this bacterium. Vit C counteracted hydrogen peroxide in honey solution and, thus, eliminated the major antibacterial compound present in honey. It is likely that a combination of honey with Vit C may trigger the intracellular production of reactive oxygen species in bacterial cells, but the exact cellular mechanisms warrant further investigations.
| S-EPMC7070301 | biostudies-literature
Project description:Antibiotic resistance poses a serious threat to global health. To reinforce the anti-infective arsenal, many novel therapeutic strategies to fight bacterial infections are being explored. Among them, anti-virulence therapies, which target pathways important for virulence, have attracted much attention. Nitric oxide (NO) defense systems have been identified as critical for the pathogenesis of various bacteria, making them an appealing therapeutic target. In this study, we performed chemical screens to identify inhibitors of NO detoxification in Escherichia coli. We found that 2-mercaptobenzothiazole (2-MBT) can potently inhibit cellular detoxification of NO, achieving a level of inhibition that resembled the effect of genetically removing Hmp, the dominant detoxification enzyme under oxygenated conditions. Further analysis revealed that in the presence of NO, 2-MBT impaired the catalysis of Hmp and synthesis of Hmp and other proteins, whereas in its absence there were minimal perturbations to growth and protein synthesis. In addition, by studying the structure-activity relationship of 2-MBT, we found that both sulfur atoms in 2-MBT were vital for its inhibition of NO detoxification. Interestingly, when 2-mercaptothiazole (2-MT), which lacked the benzene ring, was used, differing biological activities were observed, although they too were NO dependent. Specifically, 2-MT could still prohibit NO detoxification, though it did not interfere with Hmp catalysis; rather, it was a stronger inhibitor of protein synthesis and it reduced the transcript levels of hmp, which was not observed with 2-MBT. Overall, these results provide a strong foundation for further exploration of 2-MBT and 2-MT for therapeutic applications.
| S-EPMC7477088 | biostudies-literature
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is a serious human pathogen which has been listed as a high-priority multi-drug resistance pathogen by the World Health Organization (WHO). Persistent MRSA infections are often associated with biofilm formation and resistance to conventional antimicrobial therapy. Inhibiting the surface adherence and the virulence of the bacterium is the current alternative approach without affecting growth to reduce the possibility of resistance development. Although numerous antibiofilm agents have been identified, their mode of action remains unclear. Combining two drugs with different modes of action will improve the efficiency of the treatment strategy against MRSA. The present study was aimed to decipher the molecular mechanism underlying the antibiofilm activity of thymol against MRSA and assess the ability of thymol to improve the antibacterial activity of rifampicin. Thymol significantly inhibited 88% of MRSA biofilm formation at 100 ?g/ml and reduced the surface adherence of MRSA on glass, stainless steel, and titanium surface coated with human plasma as evidenced by microscopic analyses. qPCR analysis of global virulence regulatory genes and biofilm assay with S. aureus wild type, ?sarA, and ?agr strains revealed the sarA-mediated antibiofilm activity of thymol and inhibition of sarA-controlled virulence factors. Congo red assay and erythrocyte lysis assay further confirmed the reduction in polysaccharide intracellular adhesin and hemolysin. Importantly, thymol enhanced the antibacterial and the biofilm eradication efficiency of rifampicin against MRSA and also reduced the formation of persisters. Thus, the present study reveals the sarA-dependent antibiofilm efficacy of MRSA and suggests thymol as the promising combinatorial candidate in potentiating the antibacterial activity of rifampicin against persistent MRSA infections.
| S-EPMC7410925 | biostudies-literature