scholarly journals In vitroandin vivoactivities of a bi-aryl oxazolidinone RBx 11760 against Gram positive bacteria

2016 ◽  
pp. AAC.00453-16 ◽  
Author(s):  
Tarani Kanta Barman ◽  
Manoj Kumar ◽  
Tarun Mathur ◽  
Tridib Chaira ◽  
G. Ramkumar ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
High Dose ◽  
Dependent Manner ◽  
Gram Positive ◽  
Concentration Dependent Manner ◽  
Gram Positive Bacteria ◽  
Initial Control ◽  
The Difference ◽  
Time Kill ◽  
Groin Abscess

RBx 11760, a bi-aryl oxazolidinone was investigated for antibacterial activity against Gram positive bacteria. The MIC90(mg/L) of RBx 11760 and linezolid againstStaphylococcus aureuswere: 2 and 4,Staphylococcus epidermidis: 0.5 and 2,Enterococcus: 1 and 4, respectively. Similarly againstStreptococcus pneumoniaeMIC90was: 0.5 and 2, respectively. In time-kill studies, RBx 11760, tedizolid and linezolid exhibited bacteriostatic effect exceptS. pneumoniae. RBx 11760 showed 2-log10kill at 4 X MIC while tedizolid and linezolid showed 2 log10and 1.4-log10kill at 16 X MIC, respectively against MRSA H-29. AgainstS. pneumoniae5051, RBx 11760 showed bactericidal activity with 4.6 log10kill at 4 X MIC compared to 2.42 log10and 1.95 log10kill of tedizolid and linezolid at 16 X MIC. RBx 11760 showed 3 h post antibiotic effects (PAE) at 4 mg/L against MRSA H-29 and linezolid showed same effect at 16mg/L. RBx 11760 inhibited the biofilm production against MRSE ATCC 35984 in concentration dependent manner. In foreign body model, linezolid and rifampicin resulted in no advantage over stasis, while same dose of RBx 11760 demonstrated a significant killing from initial control againstS. aureus(*p<0.05) and MRSE (**p<0.01). The difference in killing was statistically significant for the lower dose of RBx 11760 (*p<0.05) versus high dose of linezolid (nsp>0.05) in groin abscess model. In neutropenic mouse thigh infection, RBx 11760 showed stasis at 20 mg/kg whereas tedizolid showed same effect at 40 mg/kg. These data support the RBx 11760 as a promising investigational candidate.

Influence of Cell Wall Composition on the Fossilisation of Bacteria and the Implications for the Search for Early Life Forms

1997 ◽  
Vol 161 ◽  
pp. 491-504 ◽  
Author(s):  
Frances Westall
Keyword(s):  
Cell Wall ◽  
Life Forms ◽  
Cation Binding ◽  
Positive Bacterium ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Transmission Electron ◽  
Hydrothermal Sediments ◽  
Identification Of Bacteria ◽  
The Difference

AbstractThe oldest cell-like structures on Earth are preserved in silicified lagoonal, shallow sea or hydrothermal sediments, such as some Archean formations in Western Australia and South Africa. Previous studies concentrated on the search for organic fossils in Archean rocks. Observations of silicified bacteria (as silica minerals) are scarce for both the Precambrian and the Phanerozoic, but reports of mineral bacteria finds, in general, are increasing. The problems associated with the identification of authentic fossil bacteria and, if possible, closer identification of bacteria type can, in part, be overcome by experimental fossilisation studies. These have shown that not all bacteria fossilise in the same way and, indeed, some seem to be very resistent to fossilisation. This paper deals with a transmission electron microscope investigation of the silicification of four species of bacteria commonly found in the environment. The Gram positiveBacillus laterosporusand its spore produced a robust, durable crust upon silicification, whereas the Gram negativePseudomonas fluorescens, Ps. vesicularis, andPs. acidovoranspresented delicately preserved walls. The greater amount of peptidoglycan, containing abundant metal cation binding sites, in the cell wall of the Gram positive bacterium, probably accounts for the difference in the mode of fossilisation. The Gram positive bacteria are, therefore, probably most likely to be preserved in the terrestrial and extraterrestrial rock record.

scholarly journals Titanium Dioxide Nanoparticles Induce Inhibitory Effects against Planktonic Cells and Biofilms of Human Oral Cavity Isolates of Rothia mucilaginosa, Georgenia sp. and Staphylococcus saprophyticus

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1564
Author(s):  
Saher Fatima ◽  
Khursheed Ali ◽  
Bilal Ahmed ◽  
Abdulaziz A. Al Kheraif ◽  
Asad Syed ◽  
...  
Keyword(s):  
Titanium Dioxide Nanoparticles ◽  
Anatase Phase ◽  
Spherical Shape ◽  
Rrna Gene ◽  
Dependent Manner ◽  
Bacterial Cells ◽  
Gram Positive ◽  
Concentration Dependent Manner ◽  
Staphylococcus Saprophyticus ◽  
Rothia Mucilaginosa

Multi-drug resistant (MDR) bacterial cells embedded in biofilm matrices can lead to the development of chronic cariogenesis. Here, we isolated and identified three Gram-positive MDR oral cocci, (1) SJM-04, (2) SJM-38, and (3) SJM-65, and characterized them morphologically, biochemically, and by 16S rRNA gene-based phylogenetic analysis as Georgenia sp., Staphylococcus saprophyticus, and Rothia mucilaginosa, respectively. These three oral isolates exhibited antibiotic-resistance against nalidixic acid, tetracycline, cefuroxime, methicillin, and ceftazidime. Furthermore, these Gram positive MDR oral cocci showed significant (p < 0.05) variations in their biofilm forming ability under different physicochemical conditions, that is, at temperatures of 28, 30, and 42 °C, pH of 6.4, 7.4, and 8.4, and NaCl concentrations from 200 to 1000 µg/mL. Exposure of oral isolates to TiO2NPs (14.7 nm) significantly (p < 0.05) reduced planktonic cell viability and biofilm formation in a concentration-dependent manner, which was confirmed by observing biofilm architecture by scanning electron microscopy (SEM) and optical microscopy. Overall, these results have important implications for the use of tetragonal anatase phase TiO2NPs (size range 5–25 nm, crystalline size 13.7 nm, and spherical shape) as an oral antibiofilm agent against Gram positive cocci infections. We suggest that TiO2NPs pave the way for further applications in oral mouthwash formulations and antibiofilm dental coatings.

scholarly journals Clinical Evaluation of the iCubate iC-GPC Assay for Detection of Gram-Positive Bacteria and Resistance Markers from Positive Blood Cultures

2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Paul A. Granato ◽  
Melissa M. Unz ◽  
Raymond H. Widen ◽  
Suzane Silbert ◽  
Stephen Young ◽  
...  
Keyword(s):  
Blood Culture ◽  
Staphylococcus Epidermidis ◽  
Bloodstream Infections ◽  
Blood Cultures ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Sequencing Method ◽  
Resistance Markers ◽  
Gram Positive Cocci

ABSTRACT The iC-GPC Assay (iCubate, Huntsville, AL) is a qualitative multiplex test for the detection of five of the most common Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Enterococcus faecalis, and Enterococcus faecium) responsible for bacterial bloodstream infections, performed directly from positive blood cultures. The assay also detects the presence of the mecA, vanA, and vanB resistance determinants. This study comparatively evaluated the performance of the iC-GPC Assay against the Verigene Gram-positive blood culture (BC-GP) assay (Luminex Corp., Austin, TX) for 1,134 patient blood culture specimens positive for Gram-positive cocci. The iC-GPC Assay had an overall percent agreement with the BC-GP assay of 95.5%. Discordant specimens were further analyzed by PCR and a bidirectional sequencing method. The results indicate that the iC-GPC Assay together with the iCubate system is an accurate and reliable tool for the detection of the five most common Gram-positive bacteria and their resistance markers responsible for bloodstream infections.

scholarly journals Advanced Quantification Methods To Improve the 18b Dormancy Model for Assessing the Activity of Tuberculosis Drugs In Vitro

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
E. D. Pieterman ◽  
M. J. Sarink ◽  
C. Sala ◽  
S. T. Cole ◽  
J. E. M. de Steenwinkel ◽  
...  
Keyword(s):  
Drug Development ◽  
Area Under The Curve ◽  
High Dose ◽  
Current Form ◽  
Content Type ◽  
Solid Media ◽  
Development Pipeline ◽  
The Difference ◽  
Time Kill

ABSTRACT One of the reasons for the lengthy tuberculosis (TB) treatment is the difficulty to treat the nonmultiplying mycobacterial subpopulation. In order to assess the ability of (new) TB drugs to target this subpopulation, we need to incorporate dormancy models in our preclinical drug development pipeline. In most available dormancy models, it takes a long time to create a dormant state, and it is difficult to identify and quantify this nonmultiplying condition. The Mycobacterium tuberculosis 18b strain might overcome some of these problems, because it is dependent on streptomycin for growth and becomes nonmultiplying after 10 days of streptomycin starvation but still can be cultured on streptomycin-supplemented culture plates. We developed our 18b dormancy time-kill kinetics model to assess the difference in the activity of isoniazid, rifampin, moxifloxacin, and bedaquiline against log-phase growth compared to the nonmultiplying M. tuberculosis subpopulation by CFU counting, including a novel area under the curve (AUC)-based approach as well as time-to-positivity (TTP) measurements. We observed that isoniazid and moxifloxacin were relatively more potent against replicating bacteria, while rifampin and high-dose bedaquiline were equally effective against both subpopulations. Moreover, the TTP data suggest that including a liquid culture-based method could be of additional value, as it identifies a specific mycobacterial subpopulation that is nonculturable on solid media. In conclusion, the results of our study underline that the time-kill kinetics 18b dormancy model in its current form is a useful tool to assess TB drug potency and thus has its place in the TB drug development pipeline.

L-Lysine: A Modulator for the Relative Activity of High Molecular Weight (HMW) and Low Molecular Weight(LHW) Urokinase(UK)

1979 ◽  
Author(s):  
L.L. Shen ◽  
W.H. Holleman
Keyword(s):  
Molecular Weight ◽  
Caproic Acid ◽  
Fibrin Clot ◽  
Relative Activity ◽  
Test Tube ◽  
Clot Lysis ◽  
Dependent Manner ◽  
Plasma Clot ◽  
Concentration Dependent Manner ◽  
The Difference

L-Lysine(Lys), in a concentration dependent manner, progressively inhibited UK-activated lysis of human plasma clots as demonstrated by Ploug test-tube method and elastometric measurements. Lys was more effective with HMW UK than LMW UK, and the effect of Lys with LMW UK from tissue culture and urine sources was the same. Epsilon amino caproic acid(EACA) and tranexamic acid(TXA) were stronger inhibitors but inhibited HMW and LMW UK-induced lysis to the same degree. Elastometric measurements showed that Lys inhibition was not due to its interference with the initial clotting process nor to the reduction of clot rigidity. Amidolytic assays using chromogenic substrates showed that Lys had no direct effect, on UK, and that Lys enhanced the activation of the native Glu-plasminogen(Pg) by LMW UK, but not the activation by HMW UK. When the substrate was human fibrin clots, Lys enhanced the lysis induced by LMW UK while the lysis induced by HMW UK was inhibited; however, the extent of enhancement and inhibition was limited. We concluded that the mode of Lys action is not identical to that of EACA or TXA, and that the stronger Lys inhibition of plasma clot lysis as compared to fibrin clot lysis is due to the potentiation of plasma fibrinolytic inhibitors by Lys. The difference In effect of Lys on HMW and LMW UK-induced lyels is likely due to a partial conformation change of Glu-Pg molecule upon Lys binding. The relatively moderate interaction of Lys with Glu-Fg results In a mildly modified UK substrate which reacts preferentially with the enzyme smaller in size.

scholarly journals Chemical Composition, and Cytotoxic, Antioxidant and Antibacterial Activities of the Essential Oil from Ginseng Leaves

2014 ◽  
Vol 9 (6) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Rui Jiang ◽  
Liwei Sun ◽  
Yanbing Wang ◽  
Jianzeng Liu ◽  
Xiaodan Liu ◽  
...  
Keyword(s):  
Essential Oil ◽  
Biological Activities ◽  
Radical Scavenging ◽  
Complex Mixture ◽  
Annexin V ◽  
Antibacterial Activities ◽  
Cytotoxic Activities ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Gram Positive Bacteria

Panax ginseng C.A.Meyer is one of the most valuable traditional Chinese medicines. In this study, the essential oil of ginseng leaves (EOGL), collected using hydrodistillation and analyzed by GC/MS, contained a complex mixture of aliphatic (69.0%), terpenoid (21.5%) and aromatic compounds (2.4%). Among 54 components identified, the major ones were palmitic acid (36.1%), β-farnesene (15.4%), linoleic acid (9.8%) and phytol (5.6%). In the cytotoxicity study, EOGL exhibited obvious cytotoxic activities against different cancer cell lines, including Hela, A549, ZR-75-1, HT-29, SGC7901 and B16 cells. Furthermore, Annexin V-FITC/PI staining assay indicated that EOGL can induce late apoptosis of ZR-75-1 cells, and the percentage of apoptotic cells increased in a concentration-dependent manner (0.9% to 5.6% and 67.4%). In addition to this, we also found that EOGL exhibited weak DPPH radical scavenging (12.0 ± 0.4 mg/mL) and ABTS radical scavenging activities (1.6 ± 0.1 mg/mL), and showed antibacterial activity against the Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and the Gram-negative bacterium, Escherichia coli. The data suggest that EOGL, which possesses important biological activities, especially significant anticancer activity, could be a potential medicinal resource.

scholarly journals In Vitro Antimicrobial Activities of Novel Anilinouracils Which Selectively Inhibit DNA Polymerase III of Gram-Positive Bacteria

2000 ◽  
Vol 44 (8) ◽  
pp. 2217-2221 ◽  
Author(s):  
Jennifer S. Daly ◽  
Theodore J. Giehl ◽  
Neal C. Brown ◽  
Chengxin Zhi ◽  
George E. Wright ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Antimicrobial Activities ◽  
Dna Polymerase Iii ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
New Agents ◽  
Gram Positive Bacteria ◽  
Polymerase Iii ◽  
Time Kill

ABSTRACT The 6-anilinouracils are novel dGTP analogs that selectively inhibit the replication-specific DNA polymerase III of gram-positive eubacteria. Two specific derivatives, IMAU (6-[3′-iodo-4′-methylanilino]uracil) and EMAU (6-[3′-ethyl-4′-methylanilino]uracil), were substituted with either a hydroxybutyl (HB) or a methoxybutyl (MB) group at their N3 positions to produce four agents: HB-EMAU, MB-EMAU, HB-IMAU, and MB-IMAU. These four new agents inhibited Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis, and Enterococcus faecium. Time-kill assays and broth dilution testing confirmed bactericidal activity. These anilinouracil derivatives represent a novel class of antimicrobials with promising activities against gram-positive bacteria that are resistant to currently available agents, validating replication-specific DNA polymerase III as a new target for antimicrobial development.

Contribution of Toll-like receptors to the innate immune response to Gram-negative and Gram-positive bacteria

Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1574-1583 ◽  
Author(s):  
Greg Elson ◽  
Irène Dunn-Siegrist ◽  
Bruno Daubeuf ◽  
Jérome Pugin
Keyword(s):  
Cell Activation ◽  
Dependent Manner ◽  
Toll Like Receptors ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Independent Manner ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Molecular Pattern ◽  
High Concentrations

Abstract Innate recognition of bacteria is a key step in the activation of inflammation and coagulation, and it is dependent on pathogen-associated molecular pattern (PAMP) ligation to Toll-like receptors (TLRs) and CD14. The dominant receptors activated when cells encounter a whole bacterium, which express several PAMPs, are poorly defined. Herein, we have stimulated various human cells with prototypic Gram-negative and Gram-positive bacteria. Receptor-dependent responses to whole bacteria were assessed using both TLR-transfected cells and specific monoclonal antibodies against TLRs, MD-2, and CD14. Enterobacteria-activated leukocytes and endothelial cells in a TLR4/MD-2–dependent manner, most likely via lipopolysaccharide (LPS). TLR2 activation was observed with a high bacterial inoculum, and in epithelial cells expressing TLR2 but not TLR4. Pseudomonas aeruginosa stimulated cells by both TLR2 and TLR4/MD-2. Gram-positive bacteria activated cells only at high concentrations, in a partially TLR2-dependent but TLR4/MD-2–independent manner. Either TLR or CD14 neutralization blocked activation to all bacterial strains tested with the exception of some Gram-positive strains in whole blood in which partial inhibition was noted. This study identifies dominant TLRs involved in responses to whole bacteria. It also validates the concept that host cell activation by bacterial pathogens can be therapeutically reduced by anti-TLR4, -TLR2, and -CD14 mAbs.

scholarly journals Evaluation of Anti-Inflammatory Activities of Qingre-Qushi Recipe (QRQS) against Atopic Dermatitis: Potential Mechanism of Inhibition of IL-33/ST2 Signal Transduction

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Mengjiao Chen ◽  
Peijun Ding ◽  
Lili Yang ◽  
Xufeng He ◽  
Chunjie Gao ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Molecular Mechanisms ◽  
Histological Study ◽  
High Dose ◽  
Dependent Manner ◽  
Hacat Cells ◽  
Concentration Dependent Manner ◽  
Dermal Thickness ◽  
Significant Difference ◽  
Anti Inflammatory

To evaluate the anti-inflammatory activities of QRQS against AD and the inhibitory molecular mechanisms of IL-33/ST2 signal transduction, BALB/c mice were divided into six groups (normal control, OVA control, low-dose of QRQS, middle-dose of QRQS, high-dose of QRQS, and cetirizine) and epicutaneously exposed to ovalbumin or PBS for 3 weeks and treated with QRQS for 2 weeks. Skin biopsies and blood samples were obtained for histological study, antibody analysis, and RNA isolation. HaCaT cells, stimulated by TNF-α and IFN-γ, were treated with QRQS to evaluate mRNA and protein expression by RT-PCR and ELISA. QRQS decreased both epidermal and dermal thickness, alleviated dermatitis, and reduced IL-33 and ST2 positive cell numbers. The concentration of specific IgE, IgG, IgG1, and IgG2a antibodies in serum and the expression of IL-33, ST2, IL-1RAcP, IL-4, and IL-13 mRNA in the skin were suppressed. No significant difference exists in TNF-α or IFN-γ. QRQS decreased IL-33 mRNA and protein secretion in HaCaT cells exposed to TNF-α and IFN-γ in a time- and concentration-dependent manner. QRQS regulates related molecule expression of ovalbumin-induced dermatitis involved in the IL-33/ST2 signaling axis in the treatment of acute AD.

scholarly journals In Vitro Activities of ME1036 (CP5609), a Novel Parenteral Carbapenem, against Methicillin-Resistant Staphylococci

2004 ◽  
Vol 48 (8) ◽  
pp. 2831-2837 ◽  
Author(s):  
Mizuyo Kurazono ◽  
Takashi Ida ◽  
Keiko Yamada ◽  
Yoko Hirai ◽  
Takahisa Maruyama ◽  
...  
Keyword(s):  
Multiple Drug ◽  
Gram Negative Bacteria ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Gram Negative ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Multiple Drug Resistant ◽  
Time Kill

ABSTRACT ME1036, formerly CP5609, is a novel parenteral carbapenem with a 7-acylated imidazo[5,1-b]thiazole-2-yl group directly attached to the carbapenem moiety of the C-2 position. The present study evaluated the in vitro activities of ME1036 against clinical isolates of gram-positive and gram-negative bacteria. ME1036 displayed broad activity against aerobic gram-positive and gram-negative bacteria. Unlike other marketed β-lactam antibiotics, ME1036 maintained excellent activity against multiple-drug-resistant gram-positive bacteria, such as methicillin-resistant staphylococci and penicillin-resistant Streptococcus pneumoniae (PRSP). The MICs of this compound at which 90% of isolates were inhibited were 2 μg/ml for methicillin-resistant Staphylococcus aureus (MRSA), 2 μg/ml for methicillin-resistant coagulase-negative staphylococci, and 0.031 μg/ml for PRSP. In time-kill studies with six strains of MRSA, ME1036 at four times the MIC caused a time-dependent decrease in the numbers of viable MRSA cells. The activity of ME1036 against MRSA is related to its high affinity for penicillin-binding protein 2a, for which the 50% inhibitory concentration of ME1036 was approximately 300-fold lower than that of imipenem. In conclusion, ME1036 demonstrated a broad antibacterial spectrum and high levels of activity in vitro against staphylococci, including β-lactam-resistant strains.

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