scholarly journals The biogenesis of extracellular vesicles fromStaphylococcus aureusand their application as a novel vaccine platform

2018 ◽  
Author(s):  
Xiaogang Wang ◽  
Christopher Weidenmaier ◽  
Jean C. Lee
Keyword(s):  
Extracellular Vesicles ◽  
Neutralizing Antibodies ◽  
Cytoplasmic Membrane ◽  
Bacterial Pathogenesis ◽  
Vaccine Platform ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Sepsis Model ◽  
Alpha Type

AbstractGram-positive bacteria secrete extracellular vesicles (EVs) that package diverse bacterial antigens and play key roles in bacterial pathogenesis. However, the mechanisms underlying EV production in Gram-positive bacteria are poorly understood. We purified and characterized EVs from a community-associated methicillin-resistantStaphylococcus aureusisolate (USA300) and investigated mechanisms underlying EV production. Native EVs contained 165 proteins, including cytosolic, surface, and secreted proteins, autolysins, and numerous cytolysins. Staphylococcal alpha-type phenol-soluble modulins (surfactant-like peptides) promoted EV biogenesis, presumably by acting at the cytoplasmic membrane, whereas peptidoglycan crosslinking and autolysin activity were found to increase EV production by altering the permeability of the staphylococcal cell wall. To address the immunogenicity of EVs, we created engineered EVs (eng-EVs) by expressing detoxified proteins HlaH35Land LukE in EVs generated from a nontoxicS. aureus ΔagrΔspamutant. Eng-EVs exhibited no cytotoxicity in vitro, and mice immunized with the eng-EVs produced toxin-neutralizing antibodies and showed reduced lethality in a mouse sepsis model. Our study reveals novel mechanisms underlyingS. aureusEV production and highlights the usefulness of EVs as a novelS. aureusvaccine platform.

scholarly journals In Vitro and In Vivo Antibacterial Activities of DW-224a, a New Fluoronaphthyridone

2006 ◽  
Vol 50 (6) ◽  
pp. 2261-2264 ◽  
Author(s):  
Hee-Soo Park ◽  
Hyun-Joo Kim ◽  
Min-Jung Seol ◽  
Dong-Rack Choi ◽  
Eung-Chil Choi ◽  
...  
Keyword(s):  
Antibacterial Activities ◽  
The Other ◽  
Vitro Activity ◽  
Gram Negative Bacteria ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

ABSTRACT DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.

scholarly journals In Vitro Characterization of the Bacillus subtilis Protein Tyrosine Phosphatase YwqE

2005 ◽  
Vol 187 (10) ◽  
pp. 3384-3390 ◽  
Author(s):  
Ivan Mijakovic ◽  
Lucia Musumeci ◽  
Lutz Tautz ◽  
Dina Petranovic ◽  
Robert A. Edwards ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Class Ii ◽  
Gram Positive ◽  
Protein Tyrosine ◽  
Gram Positive Bacteria ◽  
New Family ◽  
In Vitro Characterization

ABSTRACT Both gram-negative and gram-positive bacteria possess protein tyrosine phosphatases (PTPs) with a catalytic Cys residue. In addition, many gram-positive bacteria have acquired a new family of PTPs, whose first characterized member was CpsB from Streptococcus pneumoniae. Bacillus subtilis contains one such CpsB-like PTP, YwqE, in addition to two class II Cys-based PTPs, YwlE and YfkJ. The substrates for both YwlE and YfkJ are presently unknown, while YwqE was shown to dephosphorylate two phosphotyrosine-containing proteins implicated in UDP-glucuronate biosynthesis, YwqD and YwqF. In this study, we characterize YwqE, compare the activities of the three B. subtilis PTPs (YwqE, YwlE, and YfkJ), and demonstrate that the two B. subtilis class II PTPs do not dephosphorylate the physiological substrates of YwqE.

scholarly journals In Vitro and In Vivo Activities of DA-7867, a New Oxazolidinone, against Aerobic Gram-Positive Bacteria

2005 ◽  
Vol 49 (6) ◽  
pp. 2498-2500 ◽  
Author(s):  
Eun Jeong Yoon ◽  
Yeong Woo Jo ◽  
Sung Hak Choi ◽  
Tae Ho Lee ◽  
Jae Keol Rhee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Infection Models ◽  
Vancomycin Resistant

ABSTRACT In vitro and in vivo activities of DA-7867 were assessed against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. All isolates were inhibited by DA-7867 at ≤0.78 μg/ml, a four-times-lower concentration than that of inhibition by linezolid. For murine infection models, DA-7867 also exhibited greater efficacy than linezolid against all isolates tested.

scholarly journals Restoration of Bioactive Lantibiotic Suicin from a RemnantlanLocus of Pathogenic Streptococcus suis Serotype 2

2013 ◽  
Vol 80 (3) ◽  
pp. 1062-1071 ◽  
Author(s):  
Jian Wang ◽  
Yong Gao ◽  
Kunling Teng ◽  
Jie Zhang ◽  
Shutao Sun ◽  
...  
Keyword(s):  
Gene Promoter ◽  
Streptococcus Suis ◽  
Gene Clusters ◽  
Disulfide Bridge ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
System A ◽  
Bactericidal Activities

ABSTRACTLantibiotics are ribosomally synthesized, posttranslationally modified antimicrobial peptides. Their biosynthesis genes are usually organized in gene clusters, which are mainly found in Gram-positive bacteria, including pathogenic streptococci. Three highly virulentStreptococcus suisserotype 2 strains (98HAH33, 05ZYH33, and SC84) have been shown to contain an 89K pathogenicity island. Here, on these islands, we unveiled and reannotated a putative lantibiotic locus designatedsuiwhich contains a virulence-associated two-component regulator,suiK-suiR. In silicoanalysis revealed that the putative lantibiotic modification genesuiMwas interrupted by a 7.9-kb integron and that other biosynthesis-related genes contained various frameshift mutations. By reconstituting the intactsuiMinEscherichia colitogether with a semi-in vitrobiosynthesis system, a putative lantibiotic named suicin was produced with bactericidal activities against a variety of Gram-positive strains, including pathogenic streptococci and vancomycin-resistant enterococci. Ring topology dissection indicated that the 34-amino-acid lantibiotic contained two methyllanthionine residues and one disulfide bridge, which render suicin in an N-terminal linear and C-terminal globular shape. To confirm the function ofsuiK-suiR, SuiR was overexpressed and purified.In vitroanalysis showed that SuiR could specifically bind to thesuiAgene promoter. Its coexpression withsuiKcould activatesuiAgene promoter inLactococcus lactisNZ9000. Conclusively, we obtained a novel lantibiotic suicin by restoring its production from the remnantsuilocus and demonstrated that virulence-associated SuiK-SuiR regulates its production.

PTS 50: Past, Present and Future, or Diauxie Revisited

2015 ◽  
Vol 25 (2-3) ◽  
pp. 79-93 ◽  
Author(s):  
Joseph W. Lengeler
Keyword(s):  
Catabolite Repression ◽  
Biological Significance ◽  
Cellular Growth ◽  
Gram Positive ◽  
Gram Negative ◽  
Inducer Exclusion ◽  
Gram Positive Bacteria ◽  
Cellular Control

<b><i>Past:</i></b> The title ‘PTS 50 or The PTS after 50 years' relies on the first description in 1964 of the phosphoenolpyruvate-dependent carbohydrate:phosphotransferase system (PTS) by Kundig, Gosh and Roseman [Proc Natl Acad Sci USA 1964;52:1067-1074]. The system comprised proteins named Enzyme I, HPr and Enzymes II, as part of a novel PTS for carbohydrates in Gram-negative and Gram-positive bacteria, whose ‘biological significance remained unclear'. In contrast, studies which would eventually lead to the discovery of the central role of the PTS in bacterial metabolism had been published since before 1942. They are primarily linked to names like Epps and Gale, J. Monod, Cohn and Horibata, and B. Magasanik, and to phenomena like ‘glucose effects', ‘diauxie', ‘catabolite repression' and carbohydrate transport. <b><i>Present:</i></b> The pioneering work from Roseman's group initiated a flood of publications. The extraordinary progress from 1964 to this day in the qualitative and in vitro description of the genes and enzymes of the PTS, and of its multiple roles in global cellular control through ‘inducer exclusion', gene induction and ‘catabolite repression', in cellular growth, in cell differentiation and in chemotaxis, as well as the differences of its functions between Gram-positive and Gram-negative bacteria, was one theme of the meeting and will not be treated in detail here. <b><i>Future:</i></b> At the 1988 Paris meeting entitled ‘The PTS after 25 years', Saul Roseman predicted that ‘we must describe these interactions [of the PTS components] in a quantitative way [under] in vivo conditions'. I will present some results obtained by our group during recent years on the old phenomenon of diauxie by means of very fast and quantitative tests, measured in vivo, and obtained from cultures of isogenic mutant strains growing under chemostat conditions. The results begin to hint at the problems relating to future PTS research, but also to the ‘true science' of Roseman.

Zinc oxide microrods and nanorods: different antibacterial activity and their mode of action against Gram-positive bacteria

RSC Advances ◽  
2014 ◽  
Vol 4 (99) ◽  
pp. 56031-56040 ◽  
Author(s):  
Ilaria Rago ◽  
Chandrakanth Reddy Chandraiahgari ◽  
Maria P. Bracciale ◽  
Giovanni De Bellis ◽  
Elena Zanni ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Antibacterial Activity ◽  
Mode Of Action ◽  
Gram Positive ◽  
Gram Positive Bacteria

ZnO micro and nanorods, produced through simple and inexpensive techniques, resulted to be strong antimicrobials against Gram-positive bacteria, in vitro as well as in vivo, by altering cell outer structures like membrane and exopolysaccharides.

Działanie in vitro olejku cyprysowego (Oleum Cupressi) na bakterie beztlenowe

2019 ◽  
Vol 20 (2) ◽  
Author(s):  
Anna Kędzia ◽  
Elżbieta Hołderna-Kędzia
Keyword(s):  
Anaerobic Bacteria ◽  
Growth Control ◽  
Cupressus Sempervirens ◽  
Tannerella Forsythia ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Gram Positive Cocci ◽  
Porphyromonas Levii

Introduction. Cypress (Cupressus sempervirens L.) belongs to the family Cupressaceae. It is evergreen, and grows in Mediterranean region. The Cypress leaves and young branches are utilized to produce the essential oil. Cypress oil contain a number of components, in it α-pinene, Δ3-carene, α-terpinyl acetate, cedrol, α-terpinolene, β-myrcene, limonene, α-terpineolene, terpinen-4-ol, β-pinene, δ-cadinene and sabinene. The oil is used in therapy different diseases. It to have antimicrobial activity. Aim. The aim of the date was evaluation the susceptibility of anaerobic bacteria to Cypress oil. Material and methods. The anaerobic bacteria were isolated from patients. The 62 microorganisms, in it 36 strains of Gram-negative rods, 14 Gram-positive cocci and 12 Gram-positive rods, and 7 reference strains were tested. Susceptibility (MIC) was determined by means of plate dilution technique in Brucella agar supplemented with 5% defibrynated sheep blood, menadione and hemin. The Cypress oil was dissolved in DMSO and distilled water to obtain final following concentrations: 2.5, 5.0, 7.5, 10.0, 15.0 and 20.0 mg/ml. Inoculum containing 106 CFU per 1 ml was seeded with Steers replicator upon the agar with oil or without the oil (strains growth control). The agar plates was incubated in anaerobic condition in anaerobic jar in 37°C for 48 hrs. The MIC was interpreted as the lowest concentration of Cypress oil inhibiting the growth of tested bacteria. Results. The results indicated that from among Gram-negative rods the most susceptible to Cypress oil was the strains from genus Tannerella forsythia (MIC < 2.5-5.0 mg/ml), Bacteroides uniformis (MIC = 5.0 mg/ml), Bacteroides vulgatus and Porphyromonas asaccharolytica (MIC 5.0-7.5 mg/ml) and Porphyromonas levii (MIC = 7.5 mg/ml). The strains from genera Fusobacterium and of Bacteroides fragilis were the susceptible to 2.5-≥ 20.0 mg/ml. The Cypress oil was least active towards Prevotella and Parabacteroides strains (MIC ≥ 20.0 mg/ml).The tested Gram-positive cocci were more susceptible. The growth of the strains were inhibited by concentrations in ranges ≤ 2.5-7.5 mg/ml. The oil was minor active towards Gram-positive rods (MIC ≤ 2.5-20.0 mg/ml). Among the strains the genus of Actinomyces odontolyticus (MIC = 5.0 mg/ml) and Actinomyces viscosus (MIC ≤ 2.5-7.5 mg/ml) were the most susceptible. The growth of rods of Bifidobacterium breve was inhibited by concentrations 10.0 mg/ml. The data indicates that the Gram-negative rods were the less susceptible than Gram-positive bacteria to cypress oil. Conclusions. Among Gram-negative rods the most susceptible were the strains Tannerella forsythia, Bacteroides uniformis, Bacteroides vulgatus, Porphyromonas asaccharolytica and Porphyromonas levii. The oil was more active against Gram-positive cocci. Gram-positive anaerobic bacteria demonstrate the more susceptible to Cypress oil then Gram-positive rods.

scholarly journals In Vitro Activity of Eravacycline against Gram-Positive Bacteria Isolated in Clinical Laboratories Worldwide from 2013 to 2017

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Ian Morrissey ◽  
Stephen Hawser ◽  
Sibylle H. Lob ◽  
James A. Karlowsky ◽  
Matteo Bassetti ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Clinical Isolates ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Microdilution Method ◽  
Clinical Laboratories ◽  
Broth Microdilution Method ◽  
Doubling Dilution

ABSTRACT Eravacycline is a novel, fully synthetic fluorocycline antibiotic being developed for the treatment of serious infections, including those caused by resistant Gram-positive pathogens. Here, we evaluated the in vitro activities of eravacycline and comparator antimicrobial agents against a recent global collection of frequently encountered clinical isolates of Gram-positive bacteria. The CLSI broth microdilution method was used to determine in vitro MIC data for isolates of Enterococcus spp. (n = 2,807), Staphylococcus spp. (n = 4,331), and Streptococcus spp. (n = 3,373) isolated primarily from respiratory, intra-abdominal, urinary, and skin specimens by clinical laboratories in 37 countries on three continents from 2013 to 2017. Susceptibilities were interpreted using both CLSI and EUCAST breakpoints. There were no substantive differences (a >1-doubling-dilution increase or decrease) in eravacycline MIC90 values for different species/organism groups over time or by region. Eravacycline showed MIC50 and MIC90 results of 0.06 and 0.12 μg/ml, respectively, when tested against Staphylococcus aureus, regardless of methicillin susceptibility. The MIC90 values of eravacycline for Staphylococcus epidermidis and Staphylococcus haemolyticus were equal (0.5 μg/ml). The eravacycline MIC90s for Enterococcus faecalis and Enterococcus faecium were 0.06 μg/ml and were within 1 doubling dilution regardless of the vancomycin susceptibility profile. Eravacycline exhibited MIC90 results of ≤0.06 μg/ml when tested against Streptococcus pneumoniae and beta-hemolytic and viridans group streptococcal isolates. In this surveillance study, eravacycline demonstrated potent in vitro activity against frequently isolated clinical isolates of Gram-positive bacteria (Enterococcus, Staphylococcus, and Streptococcus spp.), including isolates collected over a 5-year period (2013 to 2017), underscoring its potential benefit in the treatment of infections caused by common Gram-positive pathogens.

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