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https://www.readbyqxmd.com/read/28904326/intravenous-polymyxins-revival-with-puzzle
#1
Yun Yu, Aihua Fei, Zengbin Wu, Chengjin Gao, Shuming Pan
With the increasing incidence of multi-drug resistant strains, especially carbapenem resistant strains, polymyxsins (mainly colistin and polymyxin B) based regimens seem to be a revival as an effective treatment of last resort in these infections. Evidence from 47 clinical trials or case series we reviewed showed that polymyxins based regimens are effective and have less toxicity compared with previous trials. When used alone, the mortality of intravenous polymyxsins ranged from 0% to 74.3%, clinical response (cure and improvement) rate was 7-82...
2017: Bioscience Trends
https://www.readbyqxmd.com/read/28900682/treatment-of-staphylococcus-aureus-infections
#2
Michael Z David, Robert S Daum
Staphylococcus aureus, although generally identified as a commensal, is also a common cause of human bacterial infections, including of the skin and other soft tissues, bones, bloodstream, and respiratory tract. The history of S. aureus treatment is marked by the development of resistance to each new class of antistaphylococcal antimicrobial drugs, including the penicillins, sulfonamides, tetracyclines, glycopeptides, and others, complicating therapy. S. aureus isolates identified in the 1960s were sometimes resistant to methicillin, a ß-lactam antimicrobial active initially against a majority S...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900186/improvement-of-the-glycoproteomic-toolbox-with-the-discovery-of-a-unique-c-terminal-cleavage-specificity-of-flavastacin-for-n-glycosylated-asparagine
#3
Alexander Pralow, Marcus Hoffmann, Terry Nguyen-Khuong, Erdmann Rapp, Udo Reichl
To determine all potential N-glycosylation sites of a glycoprotein, one central aspect of every bottom-up N-glycoproteomic strategy is to generate suitable N-glycopeptides that can be detected and analyzed by mass spectrometry. Specific proteases, such as trypsin, bear the potential of generating N-glycopeptides that either carry more than one N-glycosylation site or are too long to be readily analyzed by mass spectrometry- both due to the lack of tryptic cleavage sites near the N-glycosylation site. Here, we present a newly identified cleavage specificity of flavastacin, a protease from Flavobacterium menigosepticum, which - up to now - was only reported to cleave peptide bonds N-terminal to aspartic acid residues...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28888681/nano-reversed-phase-versus-nano-hydrophilic-interaction-liquid-chromatography-on-a-chip-in-the-analysis-of-hemopexin-glycopeptides
#4
Petr Kozlik, Miloslav Sanda, Radoslav Goldman
Analysis of the glycosylation of proteins is a challenge that requires orthogonal methods to achieve separation of the diverse glycoforms. A combination of reversed phase chromatography with tandem mass spectrometry (RP-LC-MS/MS) is one of the most powerful tools for glycopeptide analysis. In this work, we developed and compared RP-LC and hydrophilic interaction liquid chromatography (HILIC) in nanoscale on a chip combined with MS/MS in order to separate glycoforms of two peptides obtained from the tryptic digest of hemopexin...
August 26, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28887379/a-comprehensive-open-source-platform-for-mass-spectrometry-based-glycoproteomics-data-analysis
#5
Gang Liu, Kai Cheng, Chi Y Lo, Jun Li, Jun Qu, Sriram Neelamegham
Glycosylation is among the most abundant and diverse protein post-translational modifications (PTMs) identified to date. The structural analysis of this PTM is challenging due to the diverse monosaccharides which are not conserved among organisms, the branched nature of glycans, their isomeric structures, and heterogeneity in the glycan distribution at a given site. Glycoproteomics experiments have adopted the traditional high-throughput LC-MS(n) proteomics workflow to analyze site-specific glycosylation. However, comprehensive computational platforms for data analyses are scarce...
September 8, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28882727/newer-glycopeptide-antibiotics-for-treatment-of-complicated-skin-and-soft-tissue-infections-a-systematic-review-network-meta-analysis-and-cost-analysis
#6
REVIEW
Rajender Agarwal, Sarah M Bartsch, Brendan J Kelly, Malinda Prewitt, Yulun Liu, Yong Chen, Craig A Umscheid
OBJECTIVES: Skin and soft tissue infections (SSTIs) carry significant economic burden, as well as morbidity and mortality, especially when caused by methicillin-resistant Staphylococcus aureus (MRSA). Several new MRSA-active antibiotics have been developed, including semisynthetic glycopeptides (telavancin, dalbavancin and oritavancin). Of these, dalbavancin and oritavancin offer extended dosing intervals. METHODS: We performed a systematic review, network meta-analysis and cost analysis to compare the newer glycopeptides to standard care and each other for the treatment of complicated SSTIs (cSSTI)...
September 4, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28874712/pglyco-2-0-enables-precision-n-glycoproteomics-with-comprehensive-quality-control-and-one-step-mass-spectrometry-for-intact-glycopeptide-identification
#7
Ming-Qi Liu, Wen-Feng Zeng, Pan Fang, Wei-Qian Cao, Chao Liu, Guo-Quan Yan, Yang Zhang, Chao Peng, Jian-Qiang Wu, Xiao-Jin Zhang, Hui-Jun Tu, Hao Chi, Rui-Xiang Sun, Yong Cao, Meng-Qiu Dong, Bi-Yun Jiang, Jiang-Ming Huang, Hua-Li Shen, Catherine C L Wong, Si-Min He, Peng-Yuan Yang
The precise and large-scale identification of intact glycopeptides is a critical step in glycoproteomics. Owing to the complexity of glycosylation, the current overall throughput, data quality and accessibility of intact glycopeptide identification lack behind those in routine proteomic analyses. Here, we propose a workflow for the precise high-throughput identification of intact N-glycopeptides at the proteome scale using stepped-energy fragmentation and a dedicated search engine. pGlyco 2.0 conducts comprehensive quality control including false discovery rate evaluation at all three levels of matches to glycans, peptides and glycopeptides, improving the current level of accuracy of intact glycopeptide identification...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28874375/subinhibitory-dalbavancin-attenuates-exotoxin-production-from-methicillin-sensitive-and-methicillin-resistant-staphylococcus-aureus-in-vitro
#8
Sarah E Hobdey, Eva J Katahira, Pamela Dockstader, Stephen M Davidson, Laura Bond, Devin D Bolz, Amy E Bryant, Dennis L Stevens
This study investigates the effects of subinhibitory doses of the second-generation lipoglycopeptide antibiotic, dalbavancin, on Staphylococcus aureus toxin production in vitroS. aureus toxin production was compared with the natural glycopeptide antibiotic, vancomycin, and representative beta-lactam and oxazolidinone antibiotics. While neither dalbavancin nor vancomycin adversely increased toxin production, of these glycopeptide antibiotics, only dalbavancin significantly attenuated toxin production as subinhibitory concentrations...
September 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28866136/major-globally-disseminated-clonal-complexes-of-antimicrobial-resistant-enterococci-associated-with-infections-in-cancer-patients-in-brazil
#9
Barbara A Santos, Jéssica S Oliveira, Nayara T Cardoso, André V Barbosa, Silvana V Superti, Lúcia M Teixeira, Felipe P G Neves
Cancer and hematological malignancies constitute major comorbidities in enterococcal infections, but little is known about the characteristics of enterococci affecting cancer patients. The aim of this study was to characterize 132 enterococcal clinical isolates obtained from cancer patients attending a Cancer Reference Center in Brazil between April 2013 and March 2014. Susceptibility to 17 antimicrobial agents was assessed by disk diffusion method. Resistance and virulence genes were investigated by PCR. Multilocus sequence typing (MLST) was performed for selected Enterococcus faecalis and Enterococcus faecium isolates...
September 1, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28860626/topological-n-glycosylation-and-site-specific-n-glycan-sulfation-of-influenza-proteins-in-the-highly-expressed-h1n1-candidate-vaccines
#10
Yi-Min She, Aaron Farnsworth, Xuguang Li, Terry D Cyr
The outbreak of a pandemic influenza H1N1 in 2009 required the rapid generation of high-yielding vaccines against the A/California/7/2009 virus, which were achieved by either addition or deletion of a glycosylation site in the influenza proteins hemagglutinin and neuraminidase. In this report, we have systematically evaluated the glycan composition, structural distribution and topology of glycosylation for two high-yield candidate reassortant vaccines (NIBRG-121xp and NYMC-X181A) by combining various enzymatic digestions with high performance liquid chromatography and multiple-stage mass spectrometry...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28860194/the-bacterial-arginine-glycosyltransferase-effector-nleb-preferentially-modifies-fas-associated-death-domain-protein-fadd
#11
Nichollas E Scott, Cristina Giogha, Georgina L Pollock, Catherine L Kennedy, Andrew I Webb, Nicholas A Williamson, Jaclyn S Pearson, Elizabeth L Hartland
The inhibition of host innate immunity pathways is essential for the persistence of attaching and effacing (A/E) pathogens such as enteropathogenic Escherichia coli (EPEC) and Citrobacter rodentium during mammalian infections. To subvert these pathways and suppress the antimicrobial response, A/E pathogens use type III secretion systems (T3SS) to introduce effectors targeting key signaling pathways in host cells. One such effector is the arginine glycosyltransferase NleB1 (NleBCR in C. rodentium) that modifies conserved arginine residues in death domain-containing host proteins with N-acetylglucosamine (GlcNAc), thereby blocking extrinsic apoptosis signaling...
August 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28853199/bacterial-infection-triggered-acute-on-chronic-liver-failure-is-associated-with-increased-mortality
#12
Marcus M Mücke, Tatiana Rumyantseva, Victoria T Mücke, Katharina Schwarzkopf, Sabrina Joshi, Volkhard A J Kempf, Christoph Welsch, Stefan Zeuzem, Christian M Lange
BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is characterized by an acute deterioration of liver function in patients with cirrhosis in combination with recently defined organ failures. Our aim was to independently validate the prognostic value of the recently established EASL-CLIF-Consortium definition of ACLF and to identify new predictors of short-term mortality. METHODS: Patients with cirrhosis and the International Classification of Diseases, Tenth Revision diagnosis of (sub)acute liver failure were retrospectively categorized according to the EASL-CLIF-Consortium definition...
August 29, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28852604/rapid-glycopeptide-enrichment-using-cellulose-hydrophilic-interaction-reversed-phase-stagetips
#13
Yuki Ohta, Kotaro Kameda, Mei Matsumoto, Nana Kawasaki
Because the ionization efficiency for glycopeptides is lower than that of peptides in electrospray ionization, it is frequently necessary to enrich them prior to their analysis using liquid chromatography coupled with tandem mass spectrometry. Although some methods for selectively enriching glycopeptides (e.g., lectin, agarose, and cellulose methods) have been reported, they are time-consuming (procedures that require several hours) and may not be applicable to submicrogram-sized samples. Here, we report on a rapid, simple method for enriching glycopeptides in small sample amounts using cellulose hydrophilic interaction (cellulose HILIC)/reversed-phase (RP) stop-and-go extraction tips (StageTips)...
2017: Mass Spectrometry
https://www.readbyqxmd.com/read/28842020/one-step-synthesis-of-carboxyl-functionalized-metal-organic-framework-with-binary-ligands-for-highly-selective-enrichment-of-n-linked-glycopeptides
#14
QianJing Liu, Yiqin Xie, Chunhui Deng, Yan Li
Highly efficient and selective enrichment of glycopeptides from complex biosamples is vital prior to mass spectrometry analysis. In this work, a hydrophilic metal organic framework with free carboxylic groups (denoted as UiO-66-COOH) was synthesized in one step with binary ligands. Compared with pure UiO-66 with one ligand, UiO-66-COOH containing binary ligands demonstrated greater hydrophilicity and performed much better in selective enrichment of glycopeptides. The as-prepared material demonstrated excellent performance for selective enrichment of glycopeptides from tryptic digests of standard glycoproteins and practical biological samples...
December 1, 2017: Talanta
https://www.readbyqxmd.com/read/28842012/preparation-of-a-tio2-nh2-modified-maldi-plate-for-on-plate-simultaneous-enrichment-of-phosphopeptides-and-glycopeptides
#15
Haizhu Lin, Kaiping Yuan, Chunhui Deng
In this work, a TiO2 film was prepared on a MALDI plate by atomic layer deposition (ALD) technique and then modified with -NH2. The obtained TiO2-NH2 modified plate was applied for on-plate simultaneous enrichment of phosphopeptides and glycopeptides. The ALD TiO2 film displayed quite uniform morphology, and attached firmly to the MALDI plate with rather stable physical and chemical properties, which resulted in fine stability of the plate in performance. The -NH2 groups offered the film better hydrophilicity and affinity toward glycopeptides...
December 1, 2017: Talanta
https://www.readbyqxmd.com/read/28838234/structural-characterization-of-intact-glycoconjugates-by-tandem-mass-spectrometry-using-electron-induced-dissociation
#16
Y L Elaine Wong, Xiangfeng Chen, Ri Wu, Y L Winnie Hung, T-W Dominic Chan
Characterizing the structures of glycoconjungates is important because of glycan heterogeneity and structural complexity of aglycon. The presence of relatively weak glycosidic linkages leads to preferential cleavages that limit the acquisition of structural information under typical mass spectrometry dissociation conditions, such as collision-induced dissociation (CID) and infrared multiphoton dissociation. In this paper, we explored the dissociation behaviors of different members of glycoconjugates, including glycopeptides, glycoalkaloids, and glycolipids, under electron-induced dissociation (EID) conditions...
September 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28836582/influences-of-renal-function-descriptors-on-population-pharmacokinetic-modeling-of-vancomycin-in-chinese-adult-patients
#17
Xi-Wei Ji, Shuang-Min Ji, Xiao-Rong He, Xiao Zhu, Rong Chen, Wei Lu
Vancomycin, a glycopeptide antibiotic for the treatment of grampositive infections, is mainly eliminated via glomerular filtration. Thus, its therapeutic effects are affected predominantly by renal function. The aim of this study was to develop a population pharmacokinetic model of vancomycin for Chinese adult patients and to investigate the influence of different renal function descriptors on the predictability of the model. A retrospective analysis was performed based on the blood concentrations of vancomycin in 218 Chinese adult patients...
August 24, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28834212/assessment-of-appropriateness-of-an-initial-dosing-regimen-of-vancomycin-and-development-of-a-new-dosing-nomogram
#18
Seonghae Yoon, Kyoung Ryun Park, SeungHwan Lee, Sang-Hoon Song, Wan Beom Park, In-Jin Jang, Kyung-Sang Yu
Vancomycin is a glycopeptide antibiotic used to treat Gram-positive infections including methicillin-resistant Staphylococcus aureus (MRSA). The objectives of this study were to evaluate the appropriateness of the initial dosing regimen of vancomycin, identify factors to be considered in regimen selection and develop a new dosing nomogram. Therapeutic drug monitoring (TDM) data of vancomycin obtained from Seoul National University Hospital from 2011 to 2013 were included in this analysis. The vancomycin trough concentrations at steady state were estimated using Abbott's PKS software program and then categorized into three levels: subtherapeutic, therapeutic and toxic...
August 20, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28831149/engineered-production-and-evaluation-of-6-deoxy-tallysomycin-h-1-revealing-new-insights-into-the-structure-activity-relationship-of-the-anticancer-drug-bleomycin
#19
Dong Yang, Hindra, Liao-Bin Dong, Ivana Crnovcic, Ben Shen
The bleomycins (BLMs), a family of glycopeptide antibiotics, are currently used clinically in combination with a number of other agents for the treatment of malignant tumors. Other members of the BLM family include tallysomycins (TLMs), phleomycins and zorbamycin (ZBM). We previously cloned and characterized the biosynthetic gene clusters for BLMs, TLMs and ZBM. Applications of combinatorial biosynthesis strategies to the three biosynthetic machineries enabled the engineered production of several BLM analogs with unique structural characteristics and varying DNA cleavage activities, thereby providing an outstanding opportunity to study the structure-activity relationship (SAR) for the BLM family of anticancer drugs...
August 23, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28826211/high-strength-and-hydrophilic-chitosan-microspheres-for-the-selective-enrichment-of-n-glycopeptides
#20
Xiao-Mei He, Xi-Chao Liang, Xi Chen, Bi-Feng Yuan, Ping Zhou, Li-Na Zhang, Yu-Qi Feng
Protein glycosylation is an important post-translational modification that plays a crucial role in many biological processes. Because of the low abundance of glycoproteins and high complexity of clinical samples, the development of methods to selectively capture glycoproteins/glycopeptides is crucial to glycoproteomics study. In this work, a kind of highly cross-linked chitosan microspheres (CSMs) was prepared using epichlorhydrine as a cross-linker from chitosan solution in an alkaline/urea aqueous system...
August 31, 2017: Analytical Chemistry
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