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https://www.readbyqxmd.com/read/28346540/fragment-library-screening-identifies-hits-that-bind-to-the-non-catalytic-surface-of-pseudomonas-aeruginosa-dsba1
#1
Biswaranjan Mohanty, Kieran Rimmer, Róisín M McMahon, Stephen J Headey, Mansha Vazirani, Stephen R Shouldice, Mathieu Coinçon, Stephanie Tay, Craig J Morton, Jamie S Simpson, Jennifer L Martin, Martin J Scanlon
At a time when the antibiotic drug discovery pipeline has stalled, antibiotic resistance is accelerating with catastrophic implications for our ability to treat bacterial infections. Globally we face the prospect of a future when common infections can once again kill. Anti-virulence approaches that target the capacity of the bacterium to cause disease rather than the growth or survival of the bacterium itself offer a tantalizing prospect of novel antimicrobials. They may also reduce the propensity to induce resistance by removing the strong selection pressure imparted by bactericidal or bacteriostatic agents...
2017: PloS One
https://www.readbyqxmd.com/read/28345637/rattusin-structure-reveals-a-novel-defensin-scaffold-formed-by-intermolecular-disulfide-exchanges
#2
Hye Jung Min, Hyosuk Yun, Sehyeon Ji, Ganesan Rajasekaran, Jae Il Kim, Jeong-Sun Kim, Song Yub Shin, Chul Won Lee
Defensin peptides are essential for innate immunity in humans and other living systems, as they provide protection against infectious pathogens and regulate the immune response. Here, we report the solution structure of rattusin (RTSN), an α-defensin-related peptide, which revealed a novel C2-symmetric disulfide-linked dimeric structure. RTSN was synthesized by solid-phase peptide synthesis (SPPS) and refolded by air oxidation in vitro. Dimerization of the refolded RTSN (r-RTSN) resulted from five intermolecular disulfide (SS) bond exchanges formed by ten cysteines within two protomer chains...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28343091/rapid-detection-and-ruling-out-of-neonatal-sepsis-by-pcr-coupled-with-electrospray-ionization-mass-spectrometry-pcr-esi-ms
#3
Cristina Delcò, Oliver Karam, Riccardo Pfister, Alain Gervaix, Gesuele Renzi, Stéphane Emonet, Jacques Schrenzel, Klara M Posfay-Barbe
BACKGROUND: Sepsis is an important cause of morbidity and mortality in neonates and clinicians are typically required to administer empiric antibiotics while waiting for blood culture results. However, prolonged and inappropriate use of antibiotics is associated with various complications and adverse events. Better tools to rapidly rule out bacterial infections are therefore needed. AIMS: We aimed to assess the negative predictive value of PCR coupled with Electrospray Ionization Mass Spectrometry (PCR/ESI-MS) compared to conventional blood cultures in neonatal sepsis...
March 23, 2017: Early Human Development
https://www.readbyqxmd.com/read/28340759/a-label-free-and-universal-platform-for-antibiotics-detection-based-on-microchip-electrophoresis-using-aptamer-probes
#4
Lingying Zhou, Ning Gan, You Zhou, Tianhua Li, Yuting Cao, Yinji Chen
A novel label-free, universal, and high throughput aptasensor was developed based on a microchip electrophoresis (MCE) platform for automatic detection of antibiotic residues in food. Firstly, chloramphenicol (CAP) was employed as a model to be captured by its aptamer probe (Apt). Then, the partial complementary oligonucleotide of CAP's aptamer (C-DNA) was introduced into the reaction system. Because the Apt-CAP complex can't further hybrid with free C-DNA, the amount of hybrid Apt-C-DNA double strand DNA (dsDNA) was less than that without adding the target...
May 15, 2017: Talanta
https://www.readbyqxmd.com/read/28338920/dendritic-cell-expression-of-the-signaling-molecule-traf6-is-required-for-immune-tolerance-in-the-lung
#5
Daehee Han, Matthew C Walsh, Kwang Soon Kim, Sung-Wook Hong, Junyoung Lee, Jaeu Yi, Gloriany Rivas, Yongwon Choi, Charles D Surh
Immune tolerance in the lung is important for preventing hypersensitivity, such as allergic asthma. Maintenance of tolerance in the lung is established by coordinated activities of poorly understood cellular and molecular mechanisms, including participation of dendritic cells (DCs). We have previously identified DC expression of the signaling molecule TRAF6 as a non-redundant requirement for the maintenance of immune tolerance in the small intestine of mice. Because mucosal tissues share similarities in how they interact with exogenous antigens, we examined the role of DC-expressed TRAF6 in the lung...
March 11, 2017: International Immunology
https://www.readbyqxmd.com/read/28337297/protective-effect-of-a-novel-antibody-against-tlr2-on-zymosan-induced-acute-peritonitis-in-nf-%C3%AE%C2%BAb-transgenic-mice
#6
Qingjun Pan, Jun Cai, Yanxia Peng, Haiyan Xiao, Lifang Zhang, Jinying Chen, Huafeng Liu
In addition to antibiotic therapy for treatment of peritonitis, biologics have also been found to exhibit both anti-inflammatory and inflammation-resolving properties. Here, we first developed NF-κB transgenic mice with zymosan-induced acute peritonitis to investigate the effects of a novel anti-Toll-like receptor (TLR)2 antibody (anti-T20). In this mouse model, anti-T20 treatment significantly attenuated the increase of peritoneal NF-κB activity and serum levels of inflammatory cytokines, including monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, in a dose-dependent manner compared to mice treated with isotype control antibody...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28336464/new-insights-into-the-codon-usage-patterns-of-the-bactericidal-permeability-increasing-bpi-gene-across-nine-species
#7
Wei-Yun Qin, Li-Na Gan, Ri-Wei Xia, Shou-Yong Sun, Guo-Qiang Zhu, Sheng-Long Wu, Wen-Bin Bao
Bactericidal/permeability-increasing (BPI) protein is a member of a new generation of proteins known as super-antibiotics that are implicated as endotoxin neutralising agents. Non-uniform usage of synonymous codons for a specific amino acid during translation of a protein is known as codon usage bias (CUB). Analysis of CUB and compositional dynamics of coding sequences could contribute to a better understanding of the molecular mechanism and the evolution of a particular gene. In this study, we performed CUB analysis of the complete coding sequences of the BPI gene from nine different species...
March 20, 2017: Gene
https://www.readbyqxmd.com/read/28336429/insight-into-stereochemistry-of-a-new-imp-allelic-variant-imp-55-metallo-%C3%AE-lactamase-identified-in-a-clinical-strain-of-acinetobacter-baumannii
#8
Mohammad Reza Shakibaie, Omid Azizi, Fereshteh Shahcheraghi
Metallo-β-lactamases (MBLs) such as IMPs are broad-spectrum β-lactamases that inactivate virtually all β-lactam antibiotics including carbapenems. In this study, we investigated the hydrolytic activity, phylogenetic relationship, three dimensional (3D) structure including zinc binding motif of a new IMP variant (IMP-55) identified in a clinical strain of Acinetobacter baumannii (AB). AB strain 56 was isolated from an adult ICU of a teaching hospital in Kerman, Iran. It exhibited MIC 32μg/ml to imipenem and showed MBL activity...
March 20, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28336038/role-of-systemic-and-local-antibiotics-in-the-treatment-of-open-fractures
#9
REVIEW
David C Carver, Sean B Kuehn, John C Weinlein
The orthopedic community has learned much about the treatment of open fractures from the tremendous work of Ramon Gustilo, Michael Patzakis, and others; however, open fractures continue to be very difficult challenges. Type III open fractures continue to be associated with high infection rates. Some combination of systemic and local antibiotics may be most appropriate in these high-grade open fractures. Further research is still necessary in determining optimal systemic antibiotic regimens as well as the role of local antibiotics...
April 2017: Orthopedic Clinics of North America
https://www.readbyqxmd.com/read/28335466/a-specific-mixture-of-nutrients-suppresses-ovarian-cancer-a-2780-tumor-incidence-growth-and-metastasis-to-lungs
#10
Mohd Waheed Roomi, Tatiana Kalinovsky, Matthias Rath, Aleksandra Niedzwiecki
Ovarian cancer is the deadliest gynecological malignancy in women, and fifth leading cause of death. Despite advances made in chemotherapy and surgery, the average time of clinical remission is approximately 2 years and the 5-year survival rate is 45%. Thus, there is an urgent need for the development of a novel therapeutic approach to ovarian cancer treatment. We investigated the effect of a specific nutrient mixture (EPQ) containing ascorbic acid, lysine, proline, green tea extract, and quercetin on human ovarian cancer cell A-2780 in vivo and in vitro...
March 18, 2017: Nutrients
https://www.readbyqxmd.com/read/28333393/laser-generated-shockwaves-enhance-antibacterial-activity-against-biofilms-in-vitro
#11
William Yao, Edward C Kuan, Nathan C Francis, Maie A St John, Warren S Grundfest, Zachary D Taylor
BACKGROUND AND OBJECTIVES: Bacterial biofilm formation within chronic wound beds, which provides an effective barrier against antibiotics, is a known cause of recalcitrant infections and a significant healthcare burden, often requiring repeated surgical debridements. Laser-generated shockwaves (LGS) is a novel, minimally invasive, and nonthermal modality for biofilm mechanical debridement which utilizes compressive stress waves, generated by photonic absorption in thin titanium films to mechanically disrupt the biofilm...
March 23, 2017: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/28333335/saccharomyces-boulardii-cncm-i-745-restores-intestinal-barrier-integrity-by-regulation-of-e-cadherin-recycling
#12
Chloé Terciolo, Aurélie Dobric, Mehdi Ouaissi, Carole Siret, Gilles Breuzard, Françoise Silvy, Bastien Marchiori, Sébastien Germain, Renaté Bonier, Adel Hama, Roisin Owens, Dominique Lombardo, Véronique Rigot, Frédéric André
Background and Aims: Alteration in intestinal permeability is the main factor underlying the pathogenesis of many diseases affecting the gut, such as inflammatory bowel disease (IBD). Characterization of molecules targeting the restoration of intestinal barrier integrity is therefore vital for the development of alternative therapies. The yeast Saccharomyces boulardii CNCM I-745 (Sb), used to prevent and treat antibiotic-associated infectious and functional diarrhea, may have a beneficial effect in the treatment of IBD...
February 22, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28333283/rch51-a-multiply-antibiotic-resistant-acinetobacter-baumannii-st103ip-isolate-carries-resistance-genes-in-three-plasmids-including-a-novel-potentially-conjugative-plasmid-carrying-oxa235-in-transposon-tn6252
#13
Mohammad Hamidian, Steven J Nigro, Rebecca M Hartstein, Ruth M Hall
Objectives: To determine the identity and context of genes conferring antibiotic resistance in a sporadic multiply antibiotic-resistant Acinetobacter baumannii recovered at Royal Children's Hospital, Brisbane. Methods: The antibiotic resistance phenotype for 23 antibiotics was determined using disc diffusion or MIC determination. The whole-genome sequence of RCH51 was determined using the Illumina HiSeq platform. Antibiotic resistance determinants were identified using ResFinder...
March 13, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28333193/increased-activity-of-colistin-in-combination-with-amikacin-against-escherichia-coli-co-producing-ndm-5-and-mcr-1
#14
Yu-Feng Zhou, Meng-Ting Tao, Youjun Feng, Run-Shi Yang, Xiao-Ping Liao, Ya-Hong Liu, Jian Sun
Objectives: Colistin and carbapenem are two lines of last-resort antibiotics against lethal infections caused by MDR Gram-negative pathogens. The emergence of carbapenemase-positive Escherichia coli with colistin resistance poses a serious threat to public health worldwide. Here we report, for the first time (to the best of our knowledge), a novel combination therapy used for the treatment of E. coli co-producing MCR-1 and NDM-5. Methods: The MICs of colistin were determined alone and with 1-4 mg/L amikacin...
February 20, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28331309/in-vitro-and-in-vivo-drug-release-and-antibacterial-properties-of-the-novel-vancomycin-loaded-bone-like-hydroxyapatite-poly-amino-acid-scaffold
#15
Zhidong Cao, Dianming Jiang, Ling Yan, Jun Wu
Antibiotic-loaded carriers were developed to fill cavities and locally deliver antibiotics following implantation. However, the most commonly used antibiotic carrier, polymethyl methacrylate (PMMA), has many disadvantages including that it does not promote bone regeneration or conduction. Vancomycin-loaded bone-like hydroxyapatite/poly amino acid (V-BHA/PAA) was successfully fabricated by a homogeneous method, certified as biosafe and known to promote osteogenesis. To evaluate its drug-release features, the quantity of the vancomycin in the elution was obtained every 2 days after in vitro simulated body fluid immersion...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28329302/sensitization-of-gram-negative-bacilli-to-host-antibacterial-proteins
#16
Joanna Jammal, Fadia Zaknoon, Galoz Kaneti, Ayelet S Hershkovits, Amram Mor
Towards addressing the need for novel alternatives to antibiotics, we attempted to sensitize Gram-negative bacilli (GNB) to innate antibacterial protagonists. We report a lipopeptide-like sequence (C10OOc12O) that inflicted outer-membrane damages at low micromolar range, whereas measurable bacterial growth inhibition in broth medium required >10-fold higher concentrations. In serum however, C10OOc12O induced antibacterial activity in a manner suppressible by anti-complements antibodies or heat treatment, and acted synergistically with exogenous lysozyme in broth and serum media...
March 4, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28328947/a-spontaneous-mutation-in-kdsd-a-biosynthesis-gene-for-3-deoxy-d-manno-octulosonic-acid-occurred-in-a-ciprofloxacin-resistant-strain-of-francisella-tularensis-and-caused-a-high-level-of-attenuation-in-murine-models-of-tularemia
#17
Taylor Chance, Jennifer Chua, Ronald G Toothman, Jason T Ladner, Jonathan E Nuss, Jo Lynne Raymond, Fabrice V Biot, Samandra Demons, Lynda Miller, Stephanie Halasohoris, Sherry Mou, Galina Koroleva, Sean Lovett, Gustavo Palacios, Nicholas J Vietri, Patricia L Worsham, Christopher K Cote, Todd M Kijek, Joel A Bozue
Francisella tularensis, a gram-negative facultative intracellular bacterial pathogen, is the causative agent of tularemia and able to infect many mammalian species, including humans. Because of its ability to cause a lethal infection, low infectious dose, and aerosolizable nature, F. tularensis subspecies tularensis is considered a potential biowarfare agent. Due to its in vitro efficacy, ciprofloxacin is one of the antibiotics recommended for post-exposure prophylaxis of tularemia. In order to identify therapeutics that will be efficacious against infections caused by drug resistant select-agents and to better understand the threat, we sought to characterize an existing ciprofloxacin resistant (CipR) mutant in the Schu S4 strain of F...
2017: PloS One
https://www.readbyqxmd.com/read/28327271/novel-anti-staphylococcal-and-anti-biofilm-properties-of-two-anti-malarial-compounds-mmv665953-1-3-chloro-4-fluorophenyl-3-3-4-dichlorophenyl-urea-and-mmv665807-5-chloro-2-hydroxy-n-3-trifluoromethyl-phenyl-benzamide
#18
Marta Zapotoczna, Nabila Boksmati, Sinead Donohue, Baizurina Bahtiar, Ahmad Boland, Hamzah Al Somali, Alysia Cox, Hilary Humphreys, James P O'Gara, Marian Brennan, Eoghan O'Neill
PURPOSE: The treatment of device-related infections is challenging and current anti-microbial compounds have poor anti-biofilm activity. We aimed to identify and characterize novel compounds effective in the eradication of Staphylococcus aureus biofilms. METHODOLOGY: Two novel compounds, MMV665953 {1-(3-chloro-4-fluorophenyl)-3-(3,4-dichlorophenyl)urea} and MMV665807{5-chloro-2-hydroxy-N-[3-(trifluoromethyl)phenyl]benzamide}, effective in killing S. aureus biofilms, were identified by screening of the open access 'malaria box' chemical library...
March 23, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28326781/the-berkeleylactones-antibiotic-macrolides-from-fungal-coculture
#19
Andrea A Stierle, Donald B Stierle, Daniel Decato, Nigel D Priestley, Jeremy B Alverson, John Hoody, Kelly McGrath, Dorota Klepacki
A carefully timed coculture fermentation of Penicillium fuscum and P. camembertii/clavigerum yielded eight new 16-membered-ring macrolides, berkeleylactones A-H (1, 4, 6-9, 12, 13), as well as the known antibiotic macrolide A26771B (5), patulin, and citrinin. There was no evidence of the production of the berkeleylactones or A26771B (5) by either fungus when grown as axenic cultures. The structures were deduced from analyses of spectral data, and the absolute configurations of compounds 1 and 9 were determined by single-crystal X-ray crystallography...
March 22, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28326075/advantages-of-the-silkworm-as-an-animal-model-for-developing-novel-antimicrobial-agents
#20
REVIEW
Suresh Panthee, Atmika Paudel, Hiroshi Hamamoto, Kazuhisa Sekimizu
The demand for novel antibiotics to combat the global spread of multi drug-resistant pathogens continues to grow. Pathogenic bacteria and fungi that cause fatal human infections can also kill silkworms and the infected silkworms can be cured by the same antibiotics used to treat infections in the clinic. As an invertebrate model, silkworm model is characterized by its convenience, low cost, no ethical issues. The presence of conserved immune response and similar pharmacokinetics compared to mammals make silkworm infection model suitable to examine the therapeutic effectiveness of antimicrobial agents...
2017: Frontiers in Microbiology
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