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https://www.readbyqxmd.com/read/28937657/synthesis-of-2-4-diaminopyrimidine-core-based-derivatives-and-biological-evaluation-of-their-anti-tubercular-activities
#1
Yifan Ouyang, Hao Yang, Peng Zhang, Yu Wang, Sargit Kaur, Xuanli Zhu, Zhe Wang, Yutong Sun, Wei Hong, Yun Fong Ngeow, Hao Wang
Tuberculosis (TB) is a chronic, potentially fatal disease caused by Mycobacterium tuberculosis (Mtb). The dihyrofolate reductase in Mtb (mt-DHFR) is believed to be an important drug target in anti-TB drug development. This enzyme contains a glycerol (GOL) binding site, which is assumed to be a useful site to improve the selectivity towards human dihyrofolate reductase (h-DHFR). There have been previous attempts to design drugs targeting the GOL binding site, but the designed compounds contain a hydrophilic group, which may prevent the compounds from crossing the cell wall of Mtb to function at the whole cell level...
September 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28936210/novel-mutations-of-the-tetratricopeptide-repeat-domain-7a-gene-and-phenotype-genotype-comparison
#2
Reyin Lien, Yung-Feng Lin, Min-Wei Lai, Hui-Ying Weng, Ren-Chin Wu, Tang-Her Jaing, Jing-Long Huang, Shih-Feng Tsai, Wen-I Lee
The gastrointestinal tract contains the largest lymphoid organ to react with pathogenic microorganisms and suppress excess inflammation. Patients with primary immunodeficiency diseases (PIDs) can suffer from refractory diarrhea. In this study, we present two siblings who began to suffer from refractory diarrhea with a poor response to aggressive antibiotic and immunosuppressive treatment after surgical release of neonatal intestinal obstruction. Their lymphocyte proliferation was low, but superoxide production and IL-10 signaling were normal...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28935938/an-engineered-bispecific-dna-encoded-igg-antibody-protects-against-pseudomonas-aeruginosa-in-a-pneumonia-challenge-model
#3
Ami Patel, Antonio DiGiandomenico, Ashley E Keller, Trevor R F Smith, Daniel H Park, Stephanie Ramos, Katherine Schultheis, Sarah T C Elliott, Janess Mendoza, Kate E Broderick, Megan C Wise, Jian Yan, Jingjing Jiang, Seleeke Flingai, Amir S Khan, Kar Muthumani, Laurent Humeau, Lily I Cheng, Leslie Wachter-Rosati, C Kendall Stover, Niranjan Y Sardesai, David B Weiner
The impact of broad-spectrum antibiotics on antimicrobial resistance and disruption of the beneficial microbiome compels the urgent investigation of bacteria-specific approaches such as antibody-based strategies. Among these, DNA-delivered monoclonal antibodies (DMAbs), produced by muscle cells in vivo, potentially allow the prevention or treatment of bacterial infections circumventing some of the hurdles of protein IgG delivery. Here, we optimize DNA-delivered monoclonal antibodies consisting of two potent human IgG clones, including a non-natural bispecific IgG1 candidate, targeting Pseudomonas aeruginosa...
September 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28935609/novel-insights-into-the-vancomycin-resistant-enterococcus-faecalis-v583-alkylhydroperoxide-reductase-subunit-f
#4
Yew Kwang Toh, Asha Manikkoth Balakrishna, Malathy Sony Subramanian Manimekalai, Boon Bin Chionh, Ramya Ramaswamy Chettiyan Seetharaman, Frank Eisenhaber, Birgit Eisenhaber, Gerhard Grüber
The ability of the vancomycin-resistant Enterococcus faecalis (V583) to restore redox homeostasis via antioxidant defense mechanism is of importance, and knowledge into this defense is essential to understand its antibiotic-resistance and survival in hosts. The flavoprotein disulfide reductase AhpR, composed of the subunits AhpC and AhpF, represents one such vital part. Circular permutation was found to be a feature of the AhpF protein family. E. faecalis (V583) AhpF (EfAhpF) appears to be a representative of a minor subclass of this family, the typically N-terminal two-fold thioredoxin-like domain (NTD_N/C) is located at the C-terminus, whereas the pyridine nucleotide-disulfide oxidoreductase domain is encoded in the N-terminal part of its sequence...
September 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28934502/blocking-the-reca-activity-and-sos-response-in-bacteria-with-a-short-%C3%AE-helical-peptide
#5
Alexander Yakimov, Georgii Pobegalov, Irina Bakhlanova, Mikhail Khodorkovskii, Michael Petukhov, Dmitry Baitin
The RecX protein, a very active natural RecA protein inhibitor, can completely disassemble RecA filaments at nanomolar concentrations that are two to three orders of magnitude lower than that of RecA protein. Based on the structure of RecX protein complex with the presynaptic RecA filament, we designed a short first in class α-helical peptide that both inhibits RecA protein activities in vitro and blocks the bacterial SOS-response in vivo. The peptide was designed using SEQOPT, a novel method for global sequence optimization of protein α-helices...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28933634/development-of-a-multiplexed-opsonophagocytic-killing-assay-mopa-for-group-b-streptococcus
#6
Min Joo Choi, Ji Yun Noh, Hee Jin Cheong, Woo Joo Kim, Shun-Mei Lin, Yong Zhi, Jae Hyang Lim, Sangyong Lim, Ho Seong Seo, Joon Young Song
Group B Streptococcus (GBS) is a leading cause of sepsis in infants as well as chorioamnionitis in pregnant women. Opsonophagocytic killing assays (OPAs) are an essential technique in vaccine studies of encapsulated bacteria for estimating serotype-specific functional antibody levels in vitro. Here, we developed a three-fold multiplexed OPA (MOPA) to enable practical, large-scale assessment of GBS vaccine immunogenicity, including against serotypes Ia, III, and V. First, three target bacteria strains resistant to streptomycin, spectinomycin, or kanamycin were generated by natural selection through exposure to increasing antibiotic concentrations...
September 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28932266/risk-factors-for-surgical-site-infections-in-obstetrics-a-retrospective-study-in-an-ethiopian-referral-hospital
#7
Teshager Mamo, Tilaye Workneh Abebe, Tesfaye Yitna Chichiabellu, Antehun Alemayehu Anjulo
BACKGROUND: Pregnant women are at risk of infection during labor and delivery. Infection in obstetrics accounts for the second most common cause of maternal mortality next to post partum hemorrhage. Knowing the prevalence and associated risk factors would help to undertake optimal precautions and standard surgical techniques to reduce surgical site infection which poses increased hospital cost and total hospital stay of the patients. METHOD: Facility based retrospective observational study design was carried out purposively to assess the prevalence of surgical site infections and associated risk factors among mothers who had delivery related surgery at obstetric ward of Assela teaching referral hospital from April, 23, 2015 to September 5, 2015...
2017: Patient Safety in Surgery
https://www.readbyqxmd.com/read/28931629/selinene-volatiles-are-essential-precursors-for-maize-defense-promoting-fungal-pathogen-resistance
#8
Yezhang Ding, Alisa Huffaker, Tobias G Köllner, Philipp Weckwerth, Christelle A M Robert, Joseph L Spencer, Alexander E Lipka, Eric A Schmelz
To ensure food security, maize (Zea mays) is a model crop for understanding useful traits underlying stress resistance. In contrast to foliar biochemicals, root defenses limiting the spread of disease remain poorly described. To better understand below-ground defenses in the field, we performed root metabolomic profiling and uncovered unexpectedly high levels of the sesquiterpene volatile β-selinene and the corresponding non-volatile antibiotic derivative, β-costic acid. The application of metabolite-based quantitative trait loci (mQTL) mapping using bi-parental populations, genome wide association studies, and near-isogenic lines (NILs) enabled the identification of terpene synthase 21 (ZmTps21) on chromosome 9 as a β-costic acid pathway candidate gene...
September 20, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28930045/antibiotic-use-among-older-adults-on-an-acute-care-general-surgery-service
#9
André S Pollmann, Jon G Bailey, Philip J B Davis, Paul M Johnson
BACKGROUND: Antibiotics play an important role in the treatment of many surgical diseases that affect older adults, and the potential for inappropriate use of these drugs is high. Our objective was to describe antibiotic use among older adults admitted to an acute care surgical service at a tertiary care teaching hospital. METHODS: Detailed data regarding diagnosis, comorbidities, surgery and antibiotic use were retrospectively collected for patients 70 years and older admitted to an acute care surgical service...
October 1, 2017: Canadian Journal of Surgery. Journal Canadien de Chirurgie
https://www.readbyqxmd.com/read/28929815/the-challenge-of-curbing-aminoglycoside-resistance-can-antimicrobial-stewardship-programs-play-a-critical-role
#10
Vassiliki Pitiriga, Evangelia Dimitroulia, George Saroglou, Athanassios Tsakris
Aminoglycosides are useful antimicrobials, primarily for serious infections involving aerobic gram-negative pathogens. The inevitable increase in aminoglycoside resistance has led to calls for reducing levels of inappropriate aminoglycoside prescribing through the implementation of various antibiotic stewardship programs (ASPs). These programs mainly include restriction policies and aminoglycoside cycling. Although aminoglycoside resistance rates appear essential for measuring effectiveness of these interventions, most studies have focused on economic outcomes or clinical efficacy and toxicities...
September 20, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28929769/design-and-solidification-of-fast-releasing-clofazimine-nanoparticles-for-treatment-of-cryptosporidiosis
#11
Yingyue Zhang, Jie Feng, Simon A McManus, Hoang D Lu, Kurt D Ristroph, Eugene J Cho, Ellen L Dobrijevic, Hak-Kim Chan, Robert K Prud'homme
Clofazimine, a lipophilic (log P = 7.66) riminophenazine antibiotic approved by the US Food and Drug Administration (FDA) with a good safety record, was recently identified as a lead hit for cryptosporidiosis through a high-throughput phenotypic screen. Cryptosporidiosis requires fast-acting treatment as it leads to severe symptoms which, if untreated, result in morbidity for infants and small children. Consequently, a fast-releasing oral formulation of clofazimine in a water-dispersible form for pediatric administration is highly desirable...
September 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28927382/a-rapid-seamless-method-for-gene-knockout-in-pseudomonas-aeruginosa
#12
Weiliang Huang, Angela Wilks
BACKGROUND: Pseudomonas aeruginosa is a model organism for the study of quorum sensing, biofilm formation, and also leading cause of nosocomial infections in immune compromised patients. As such P. aeruginosa is one of the most well studied organisms in terms of its genetics. However, the construction of gene deletions and replacements in Pseudomonas aeruginosa is relatively time-consuming, requiring multiple steps including suicide vector construction, conjugation, inactivation with insertion of antibiotic resistance cassettes and allelic exchange...
September 19, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28925959/preventing-surgical-site-infections-using-a-natural-biodegradable-antibacterial-coating-on-surgical-sutures
#13
Jochen Reinbold, Ann-Kristin Uhde, Ingrid Müller, Tobias Weindl, Jürgen Geis-Gerstorfer, Christian Schlensak, Hans-Peter Wendel, Stefanie Krajewski
Surgical site infections (SSIs) are one of the most common nosocomial infections, which can result in serious complications after surgical interventions. Foreign materials such as implants or surgical sutures are optimal surfaces for the adherence of bacteria and subsequent colonization and biofilm formation. Due to a significant increase in antibiotic-resistant bacterial strains, naturally occurring agents exhibiting antibacterial properties have great potential in prophylactic therapies. The aim of this study was to develop a coating for surgical sutures consisting of the antibacterial substance totarol, a naturally occurring diterpenoid isolated from Podocarpustotara in combination with poly(lactide-co-glycolide acid) (PLGA) as a biodegradable drug delivery system...
September 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28923757/clinical-practice-and-infrastructure-review-of-fecal-microbiota-transplantation-for-clostridium-difficile-infection
#14
REVIEW
Brendan J Kelly, Pablo Tebas
A significant proportion of C. difficile infection (CDI) cases recur after completion of antibiotic therapy, and antibiotic cure rates diminish with each recurrence of CDI. Fecal microbiota transplantation (FMT) is an effective therapy for recurrent FMT, which otherwise requires prolonged or indefinite antibiotic treatment. FMT is performed by introducing the fecal microbial community obtained from a healthy donor or pool of donors into the stomach, small intestine, or colon of a patient with CDI. Multiple clinical trials support the utility of FMT in treating recurrent CDI, and CDI treatment guidelines now include consideration of FMT at the third CDI recurrence...
September 15, 2017: Chest
https://www.readbyqxmd.com/read/28923470/tripodal-lipoprotein-variants-with-c-terminal-hydrophobic-residues-allosterically-modulate-activity-of-the-degp-protease
#15
Hyojin Park, Yurie T Kim, Chulwon Choi, Seokhee Kim
DegP, a member of the highly conserved HtrA family of proteases, performs a regulated proteolysis of toxic misfolded proteins in the periplasm of Gram-negative bacteria. The allosteric switch between inactive and active conformations is a central mechanism to carefully control proteolytic activity of DegP and to maintain the optimal cellular fitness, but few other molecules than substrates are known to allosterically control DegP activity. Here, we demonstrate that a mutant variant of an outer membrane lipoprotein, Lpp(+Leu), can function as a novel allosteric effector that changes the dynamic range of DegP activity...
September 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28922811/a-programme-to-create-short-course-chemotherapy-for-pulmonary-mycobacterium-avium-disease-based-on-pharmacokinetics-pharmacodynamics-and-mathematical-forecasting
#16
Devyani Deshpande, Shashikant Srivastava, Tawanda Gumbo
Objectives: Pulmonary Mycobacterium avium complex (MAC) prevalence is on the rise worldwide. The average therapy duration is 1.5 years, which is associated with poor cure rates. Our objective was to develop a programme to design a combination therapy regimen for pulmonary MAC to be administered for 6 months or less with efficacy in > 90% of patients. Methods: We performed a literature search for the following MeSH headings 'Mycobacterium avium' AND 'pharmacokinetics/pharmacodynamics' in PubMed up to 2016...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922807/tedizolid-is-highly-bactericidal-in-the-treatment-of-pulmonary-mycobacterium-avium-complex-disease
#17
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Pooi S Lee, Tawanda Gumbo
Objectives: To determine if tedizolid is effective for pulmonary Mycobacterium avium complex (MAC) disease, and to use pharmacokinetics/pharmacodynamics to design optimal doses. Methods: We performed an exposure-response experiment in the hollow-fibre system model of intracellular MAC (HFS-MAC). We mimicked the tedizolid concentration-time profiles achieved in the lungs of patients treated once daily for 28 days. The HFS-MAC was sampled at intervals to determine the tedizolid pharmacokinetics and MAC intracellular burden...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28921938/prostate-cancer-treatment-in-renal-transplant-recipients-a-systematic-review
#18
REVIEW
Giancarlo Marra, Ettore Dalmasso, Marco Angello, Stefania Munegato, Andrea Bosio, Omidreza Sedigh, Luigi Biancone, Paolo Gontero
BACKGROUND: The majority of kidney transplants are performed in recipients (RTR) over 50; simultaneously their life expectancy is improving. The increasing age and number of RTR is likely to be paralleled by an increase of prostate cancer (PCa) incidence. However, little is known on the optimal management of these patients who represent a therapeutic challenge due to medical and anatomical graft-related issues. METHODS: AMED, Medline and Embase were searched until November 17(th) , 2016 adhering to the PRISMA guidelines and the AMSTAR checklist to investigate oncological and functional outcomes of PCa treatment in RTR...
September 18, 2017: BJU International
https://www.readbyqxmd.com/read/28917799/a-reagentless-and-reusable-electrochemical-aptamer-based-sensor-for-rapid-detection-of-ampicillin-in-complex-samples
#19
Zhi-Gang Yu, Rebecca Y Lai
We report the design and fabrication of a "signal-on" electrochemical aptamer-based (E-AB) sensor for detection of ampicillin. The signaling of the sensor is based on target binding-induced changes in the conformation and flexibility of the methylene blue-modified aptamer probe. The sensor's response is fast; signal saturation can be reached in ~ 200s. Since all the sensor components are surface-immobilized, it is regenerable and can be reused for at least three times. It has demonstrated good specificity and is capable of differentiating between ampicillin and structurally similar antibiotics such as amoxicillin...
January 1, 2018: Talanta
https://www.readbyqxmd.com/read/28916044/antibiotic-affinity-strategy-for-bioluminescent-detection-of-viable-gram-positive-bacteria-using-daptomycin-as-recognition-agent
#20
Mengyao Wang, Yue Wu, Yong He, Xiaoxiao Su, Hui Ouyang, Zhifeng Fu
A bioluminescent method was proposed for rapid detection of viable Gram-positive bacteria based on a novel antibiotic-affinity strategy on a magnetic beads (MBs) platform. Daptomycin, a highly efficient lipopeptide antibiotic for Gram-positive bacteria, was used as a recognition agent to functionalize MBs. The daptomycin-functionalized MBs showed high capture and concentration efficiency for Gram-positive bacteria due to the strong binding between daptomycin and bacterial cell membrane in the presence of Ca(2+) ion...
September 22, 2017: Analytica Chimica Acta
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