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https://www.readbyqxmd.com/read/28926596/bifurcation-kinetics-of-drug-uptake-by-gram-negative-bacteria
#1
David A Westfall, Ganesh Krishnamoorthy, David Wolloscheck, Rupa Sarkar, Helen I Zgurskaya, Valentin V Rybenkov
Cell envelopes of many bacteria consist of two membranes studded with efflux transporters. Such organization protects bacteria from the environment and gives rise to multidrug resistance. We report a kinetic model that accurately describes the permeation properties of this system. The model predicts complex non-linear patterns of drug uptake complete with a bifurcation, which recapitulate the known experimental anomalies. We introduce two kinetic parameters, the efflux and barrier constants, which replace those of Michaelis and Menten for trans-envelope transport...
2017: PloS One
https://www.readbyqxmd.com/read/28925886/the-microbiota-gut-brain-axis-in-neuropsychiatric-disorders-pathophysiological-mechanisms-and-novel-treatments
#2
Yong-Ku Kim, Cheolmin Shin
BACKGROUND: The human gut microbiome comprise a huge number of microorganisms with co-evolutionary associations with humans. It has been repeatedly revealed that bidirectional communication exists between the brain and the gut and involves neural, hormonal, and immunological pathways. Evidences from neuroscience researches over the past few years suggest that microbiota is essential for the development and maturation of brain systems that are associated to stress responses. METHOD: This review provides that the summarization of the communication among microbiota, gut and brain and the results of preclinical and clinical studies on gut microbiota used in treatments for neuropsychiatric disorders...
September 15, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28925284/ligand-design-for-riboswitches-an-emerging-target-class-for-novel-antibiotics
#3
Illimar Hugo Rek, Ruth Brenk
Riboswitches are cis-acting gene regulatory elements and constitute potential targets for new antibiotics. Recent studies in this field have started to explore these targets for drug discovery. New ligands found by fragment screening, design of analogs of the natural ligands or serendipitously by phenotypic screening have shown antibacterial effects in cell assays against a range of bacteria strains and in animal models. In this review, we highlight the most advanced drug design work of riboswitch ligands and discuss the challenges in the field with respect to the development of antibiotics with a new mechanism of action...
September 19, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28924162/insights-into-the-functionality-of-endophytic-actinobacteria-with-a-focus-on-their-biosynthetic-potential-and-secondary-metabolites-production
#4
Ajit Kumar Passari, Vineet Kumar Mishra, Garima Singh, Pratibha Singh, Brijesh Kumar, Vijai Kumar Gupta, Rupak Kumar Sharma, Ratul Saikia, Anthonia O' Donovan, Bhim Pratap Singh
Endophytic actinobacteria play an important role in growth promotion and development of host plant by producing enormous quantities of novel bioactive natural products. In the present investigation, 169 endophytic actinobacteria were isolated from endospheric tissues of Rhynchotoechum ellipticum. Based on their antimicrobial potential, 81 strains were identified by 16rRNA gene analysis, which were taxonomically grouped into 15 genera. All identified strains were screened for their plant growth promoting attributes and, for the presence of modular polyketide synthases (PKSI, PKSII and nonribosomal peptide synthetase (NRPS) gene clusters to correlate the biosynthetic genes with their functional properties...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923876/co-location-of-the-multiresistance-gene-cfr-and-the-fosfomycin-resistance-gene-fosd-on-a-novel-plasmid-in-staphylococcus-arlettae-from-chicken-farm
#5
Bi-Hui Liu, Chang-Wei Lei, An-Yun Zhang, Yun Pan, Ling-Han Kong, Rong Xiang, Yong-Xiang Wang, Yan-Xian Yang, Hong-Ning Wang
A novel 63,558-bp plasmid pSA-01 harbouring nine antibiotic resistance genes, including cfr, erm(C), tet(L), erm(T), aadD, fosD, fexB, aacA-aphD and erm(B), was characterized in Staphylococcus arlettae strain SA-01 isolated from chicken farm in China. The co-location of cfr and fosD genes was detected for the first time in S. arlettae plasmid. The detection of two IS431-mediated circular forms containing resistance genes in SA-01 suggested that IS431 may facilitate dissemination of antibiotic resistance genes...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28923604/study-on-the-excision-and-integration-mediated-by-class-1-integron-in-streptococcus-pneumoniae
#6
Qun Lin, Pusheng Xu, Jiaowu Li, Jinhua Huang, Yin Chen, Shuhuan Deng
As a novel antibiotic resistance mobile element, integron was recognized as a primary source of antibiotic genes among Gram-positive organisms for its excision and integration of exogenous genes. In this study, Streptococcus pneumoniae was subjected to investigate the excision and integration of class 1 integron with eight different plasmids. As the results indicated, excision in both att site and gene cassettes were successfully observed, which was further confirmed by integration assays and PCR amplification...
September 16, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28923470/tripodal-lipoprotein-variants-with-c-terminal-hydrophobic-residues-allosterically-modulate-activity-of-the-degp-protease
#7
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/28922502/the-three-component-system-esrisr-regulates-a-cell-envelope-stress-response-in-corynebacterium-glutamicum
#8
Britta Kleine, Ava Chattopadhyay, Tino Polen, Daniela Pinto, Thorsten Mascher, Michael Bott, Melanie Brocker, Roland Freudl
When the cell envelope integrity is compromised, bacteria trigger signaling cascades resulting in the production of proteins that counteract these extracytoplasmic stresses. Here, we show that the two-component system EsrSR regulates a cell envelope stress response in the Actinobacterium Corynebacterium glutamicum. The sensor kinase EsrS possesses an amino-terminal phage shock protein C (PspC) domain, a property that sets EsrSR apart from all other two-component systems characterized so far. An integral membrane protein, EsrI, whose gene is divergently transcribed to the esrSR gene locus and which interestingly also possesses a PspC domain, acts as an inhibitor of EsrSR under non-stress conditions...
September 18, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28921079/identification-of-a-new-isoindole-2-yl-scaffold-as-a-qo-and-qi-dual-inhibitor-of-cytochrome-bc-1-complex-virtual-screening-synthesis-and-biochemical-assay
#9
Homa Azizian, Kowsar Bagherzadeh, Sophia Shahbazi, Niusha Sharifi, Massoud Amanlou
Respiratory chain ubiquinol-cytochrome (cyt) c oxidoreductase (cyt bc 1 or complex III) has been demonstrated as a promising target for numerous antibiotics and fungicide applications. In this study, a virtual screening of NCI diversity database was carried out in order to find novel Qo/Qi cyt bc 1 complex inhibitors. Structure-based virtual screening and molecular docking methodology were employed to further screen compounds with inhibition activity against cyt bc 1 complex after extensive reliability validation protocol with cross-docking method and identification of the best score functions...
September 18, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28919737/bacterial-membrane-vesicles-as-novel-nanosystems-for-drug-delivery
#10
REVIEW
Sapna Jain, Jonathan Pillai
Bacterial membrane vesicles (BMVs) are closed spherical nanostructures that are shed naturally and ubiquitously by most bacterial species both in vivo and in vitro. Researchers have elucidated their roles in long-distance transport of a wide array of cargoes, such as proteins, toxins, antigens, virulence factors, microbicidal agents and antibiotics. Given that these natural carriers are important players in intercellular communication, it has been hypothesized that they are equally well attuned for transport and delivery of exogenous therapeutic cargoes...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28918656/diagnosing-kingella-kingae-infections-in-infants-and-young-children
#11
Pablo Yagupsky
Kingella kingae is currently recognized as the prime etiology of skeletal system infections in children aged 6-48 months. The organism is notoriously fastidious, its growth is inhibited by synovial fluid and bone exudates, and its presence in clinical specimens is commonly missed by traditional culture methods. Areas covered. The present review discusses the use of improved laboratory methods to detect the organism in normally sterile body fluids, exudates, and upper respiratory tract specimens. Expert commentary...
September 18, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28918655/what-not-to-do-in-acute-otitis-media-the-top-five-recommendations-proposed-by-the-italian-society-of-preventive-and-social-pediatrics
#12
Elena Chiappini, Barbara Bortone, Mattia Doria, Massimo Landi, Giuseppe Di Mauro, Paola Marchisio
With the aim to reduce inappropriate procedures and antibiotic therapy in the management of acute otitis media (AOM) in children, the Italian Society of Preventive and Social Pediatrics (SIPPS) proposed a top five list of recommendations for clinical practice. Areas covered: AOM is one of the most frequent reasons for antibiotic prescription in pediatric age. The over-estimation of AOM is associated with inappropriate treatment, increased costs, adverse events and spread of antibiotic resistance. Thus, the most recent guidelines provided stringent diagnostic criteria and considered the 'watchful waiting' approach, limiting the immediate antibiotic therapy to a well-characterized subgroup of children...
September 19, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28916044/antibiotic-affinity-strategy-for-bioluminescent-detection-of-viable-gram-positive-bacteria-using-daptomycin-as-recognition-agent
#13
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
https://www.readbyqxmd.com/read/28915357/a-i-yigp-i-mutant-strain-is-a-small-colony-variant-of-i-e-coli-i-and-shows-pleiotropic-antibiotic-resistance
#14
Hui Xia, Qiongwei Tang, Jie Song, Jiang Ye, Haizhen Wu, Huizhan Zhang
Small colony variants (SCVs) are a commonly observed subpopulation of bacteria that have a small colony size and distinctive biochemical characteristics. SCVs are more resistant to some antibiotics than the wild-type, and usually cause persistent infections in the clinic. SCV studies have been very active during the past two decades, especially of <i>Staphylococcus aureus</i>. However, fewer studies on <i>Escherichia coli </i>SCVs exist, so we studied an <i>E. coli </i>SCV during an experiment involving the deletion of the<i> yigP</i> locus...
September 15, 2017: Canadian Journal of Microbiology
https://www.readbyqxmd.com/read/28914989/encapsulating-active-pharmaceutical-ingredients-in-self-assembling-adamantanes-with-short-dna-zippers
#15
Clemens Richert, Helmut Griesser, Alexander Schwenger
Formulating pharmaceutically active ingredients for drug delivery is a challenge. There is a need for new drug delivery systems that take up therapeutic molecules and release them into biological systems. We propose a novel mode of encapsulation that involves matrices formed through co-assembly of drugs with adamantane hybrids that feature four CG dimers as sticky ends. Such adamantanes are accessible via inexpensive solution-phase syntheses, and the resulting materials show attractive properties for controlled release...
September 15, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28912880/spectroscopic-analysis-and-docking-simulation-on-the-recognition-and-binding-of-tem-1-%C3%AE-lactamase-with-%C3%AE-lactam-antibiotics
#16
Jianting Yang, Qian Li, Liujiao Bian
The interaction between TEM-1 β-lactamase and antibiotics is very important in the hydrolysis of antibiotics. In the present study, the recognition and binding of TEM-1 β-lactamase with three β-lactam antibiotics, including penicillin G, cefalexin and cefoxitin, was investigated by fluorescence and ultraviolet-visible absorption spectra in combination with molecular docking in the temperature range of 278-288 K and under simulated physiological conditions. The results demonstrated that the fluorescence emissions of TEM-1 β-lactamase were extinguished by static quenching and the energy of TEM-1 β-lactamase was transferred in a non-radioactive manner...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28912539/diphenyleneiodonium-chloride-dpic-displays-broad-spectrum-bactericidal-activity
#17
Manitosh Pandey, Alok Kumar Singh, Ritesh Thakare, Sakshi Talwar, Pratiksha Karaulia, Arunava Dasgupta, Sidharth Chopra, Amit Kumar Pandey
Indiscriminate use of antibiotics globally has lead to an increase in emergence of drug-resistant pathogens under both nosocomial, as well as more worryingly, in community setting as well. Further, a decrease in the corporate interest and financial commitment has exerted increasing pressure on a rapidly dwindling antimicrobial drug discovery and developmental program. In this context, we have screened the Library of Pharmacologically Active Compounds (LOPAC, Sigma) against Staphylococcus aureus and Mycobacterium tuberculosis to identify potent novel antimicrobial molecules amongst non-antibiotic molecules...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28910076/gold-decorated-porous-silicon-nanopillars-for-targeted-hyperthermal-treatment-of-bacterial-infections
#18
Hashim Alhmoud, Anna Cifuentes-Rius, Bahman Delalat, David G Lancaster, Nicolas H Voelcker
In order to address the issue of pathogenic bacterial colonization of diabetic wounds, a more direct and robust approach is required, which relies on a physical form of bacterial destruction in addition to the conventional biochemical approach (i.e. antibiotics). Targeted bacterial destruction through the use of photothermally active nanomaterials has recently come into the spotlight as a viable approach to solving the rising problem of antibiotic resistant microorganisms. Materials with high absorption coefficients in the near infrared (NIR) region of the electromagnetic spectrum show promise as alternative antibacterial therapeutic agents, since they preclude the development of bacterial resistance and can be activated on demand...
September 14, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28905944/snakebite-envenoming
#19
REVIEW
José María Gutiérrez, Juan J Calvete, Abdulrazaq G Habib, Robert A Harrison, David J Williams, David A Warrell
Snakebite envenoming is a neglected tropical disease that kills >100,000 people and maims >400,000 people every year. Impoverished populations living in the rural tropics are particularly vulnerable; snakebite envenoming perpetuates the cycle of poverty. Snake venoms are complex mixtures of proteins that exert a wide range of toxic actions. The high variability in snake venom composition is responsible for the various clinical manifestations in envenomings, ranging from local tissue damage to potentially life-threatening systemic effects...
September 14, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28905708/williamwhitmania-taraxaci-gen-nov-sp-nov-a-proteolytic-anaerobe-with-a-novel-type-of-cytology-from-lake-untersee-in-antarctica-description-of-williamwhitmaniaceae-fam-nov-and-emendation-of-the-order-bacteroidales-krieg-2012
#20
Elena V Pikuta, Zhe Lyu, Richard B Hoover, Yuchen Liu, Nisha B Patel, Hans J Busse, Paul A Lawson
The proteolytic bacterium strain A7P-90mT was isolated from Lake Untersee, Antarctica. The anoxic water was collected from a perennially sealed (~100 millennia) glacial ice lake. Gram-stain-negative cells were 0.18-0.3×8.0-25.0 µm in size, straight, slender rods with unusual gliding motility by external, not previously reported, organelles named here as antiae. At the end of stationary phase of growth, spheroplasts were terminally formed and the cells resembled dandelions. After death, cells were helical...
September 14, 2017: International Journal of Systematic and Evolutionary Microbiology
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