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https://www.readbyqxmd.com/read/28433743/the-antibiotic-polymyxin-b-exhibits-novel-antifungal-activity-against-fusarium-species
#1
Li-Hang Hsu, Hsuan-Fu Wang, Pei-Lun Sun, Fung-Rong Hu, Ying-Lien Chen
The genus Fusarium comprises many species, including Fusarium oxysporum, Fusarium solani, Fusarium graminearum and Fusarium verticillioides, and causes severe infections in plants and humans. In clinical settings, Fusarium is the third most frequent mould to cause invasive fungal infections after Aspergillus and the Mucorales. Fusarium solani and F. oxysporum are the most prevalent Fusarium spp. causing clinical disease. However, few effective antifungal drugs are available to treat human and plant Fusarium infections...
April 19, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28432959/molecular-dynamics-simulation-studies-of-novel-%C3%AE-lactamase-inhibitor
#2
Farhan Ul Haq, Asma Abro, Saad Raza, Klaus R Liedl, Syed Sikander Azam
New Delhi Metallo-β-Lactamase-1 (NDM-1) has drawn great attention due to its diverse antibiotic resistant activity. It can hydrolyze almost all clinically available β-lactam antibiotics. To inhibit the activity of NDM-1 a new strategy is proposed using computational methods. Molecular dynamics (MD) simulations are used to analyze the molecular interactions between selected inhibitor candidates and NDM-1 structure. The enzyme-ligand complex is subject to binding free energy calculations using MM(PB/GB)SA methods...
April 4, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28432048/solithromycin-a-novel-ketolide-antibiotic
#3
Michael J Buege, Jack E Brown, Samuel L Aitken
PURPOSE: The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, clinical safety, and current regulatory status of solithromycin are reviewed. SUMMARY: Solithromycin is a novel ketolide antibiotic developed for the treatment of community-acquired bacterial pneumonia (CABP). Its pharmacologic, pharmacokinetic, and pharmacodynamic properties provide activity against a broad range of intracellular organisms, including retained activity against pathogens displaying various mechanisms of macrolide resistance...
April 21, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28431088/stationary-phase-genes-upregulated-by-polyamines-are-responsible-for-the-formation-of-escherichia-coli-persister-cells-tolerant-to-netilmicin
#4
Alexander G Tkachenko, Natalya M Kashevarova, Elena A Tyuleneva, Mikhail S Shumkov
Persisters are rare phenotypic variants of regular bacterial cells that survive lethal antibiotics or stresses owing to slowing down of their metabolism. Recently, we have shown that polyamine putrescine can upregulate persister cell formation in Escherichia coli via the stimulation of rpoS expression, encoding a master regulator of general stress response. We hypothesized that rmf and yqjD, the stationary-phase genes responsible for ribosome inactivation, might be good candidates for the similar role owing to their involvement in translational arrest and the ability to be affected by polyamines...
April 19, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28429505/total-synthesis-of-albocycline
#5
Vijay K Chatare, Rodrigo B Andrade
The macrolactone natural product (-)-albocycline is a promising antibiotic candidate for the treatment of both methicillin resistant Staphylococcus aureus (MRSA) and vancomycin-resistant strains. Herein we report a concise total synthesis of (-)-albocycline in 14 steps from commercially available methyl (R)-3-hydroxybutyrate. Novel key steps include the highly regio- and stereoselective reactions of chiral N-sulfinyl metallodienamines (NSMDs) with aldehydes and the Davis oxaziridine, in addition to the Horner-Wadsworth-Emmons olefination of N-sulfinyl imines...
April 21, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28428950/endogenous-and-exogenous-kdpf-peptide-increases-susceptibility-of-mycobacterium-bovis-bcg-to-nitrosative-stress-and-reduces-intramacrophage-replication
#6
Mariana Rosas Olvera, Eric Vivès, Virginie Molle, Anne-Béatrice Blanc-Potard, Laila Gannoun-Zaki
Emerging antibiotic resistance in pathogenic bacteria like Mycobacterium sp., poses a threat to human health and therefore calls for the development of novel antibacterial strategies. We have recently discovered that bacterial membrane peptides, such as KdpF, possess anti-virulence properties when overproduced in pathogenic bacterial species. Overproduction of the KdpF peptide in Mycobacterium bovis BCG decreased bacterial replication within macrophages, without presenting antibacterial activity. We propose that KdpF functions as a regulatory molecule and interferes with bacterial virulence, potentially through interaction with the PDIM transporter MmpL7...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28428067/targeting-and-synergistic-action-of-an-antifungal-peptide-in-an-antibiotic-drug-delivery-system
#7
Seong-Cheol Park, Young-Min Kim, Jong-Kook Lee, Nam-Hong Kim, Eun-Ji Kim, Hun Heo, Min-Young Lee, Jung Ro Lee, Mi-Kyeong Jang
Amphotericin B (AmB) has been widely used against fungal infections throughout almost the entire body, including the skin, nails, oral cavity, respiratory tract, and urinary tract. However, the development of AmB-loaded nanoparticles demands a novel technique that reduces its toxicity and other associated problems. Here, we developed a pH-responsive and redox-sensitive polymer-based AmB-delivery carrier system. In particular, this system was functionalized by conjugation with the antifungal peptide histatin 5, which acts both as a targeting ligand and a synergistic antifungal molecule against Candida albicans, a major systemic fungal pathogen of humans...
April 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28427639/synergistic-degradation-of-antibiotic-norfloxacin-in-a-novel-heterogeneous-sonochemical-fe-0-tetraphosphate-fenton-like-system
#8
Tao Zhou, Xiaoli Zou, Xiaohui Wu, Juan Mao, Jia Wang
In this study, synergistic degradation of antibiotic norfloxacin (NOR) was obtained in a novel sonochemical ultrasound/zero-valent iron/tetraphosphate system (US/ZVI/TPP). Compared to three common organic ligands (EDTA, EDDS, and DTPA), TPP could perform more excellently in activation of O2 to produce reactive oxidative species (ROS) and lead to efficient Fenton-like oxidative degradation of NOR in the sonochemical in situ chemical oxidation (ISCO) system. An optimized initial condition was obtained as 10mg/L NOR, 0...
July 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28427561/molecular-targets-of-ascochlorin-and-its-derivatives-for-cancer-therapy
#9
Jason Chua Min-Wen, Benjamin Chua Yan-Jiang, Srishti Mishra, Xiaoyun Dai, Junji Magae, Ng Shyh-Chang, Alan Prem Kumar, Gautam Sethi
Cancer is an extremely complex disease comprising of a multitude of characteristic hallmarks that continue to evolve with time. At the genomic level, random mutations leading to deregulation of diverse oncogenic signal transduction cascades and polymorphisms coupled with environmental as well as life style-related factors are major causative agent contributing to chemoresistance and the failure of conventional therapies as well as molecular targeted agents. Hence, there is an urgent need to identify novel alternative therapies based on alternative medicines to combat this dreaded disease...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28426995/antibacterial-activity-of-n-methylbenzofuro-3-2-b-quinoline-and-n-methylbenzoindolo-3-2-b-quinoline-derivatives-and-study-of-their-mode-of-action
#10
Ning Sun, Ruo-Lan Du, Yuan-Yuan Zheng, Bao-Hua Huang, Qi Guo, Rui-Fang Zhang, Kwok-Yin Wong, Yu-Jing Lu
The emergence of multidrug-resistant bacteria causes an urgent need for new generation of antibiotics, which may have a different mechanism of inhibition or killing action from the existing. Targeting at the inhibition of bacterial cell division via the control of FtsZ function is one of the effective and promising approaches. Some natural extracts from plants such as sanguinarine and berberine (analogs of pyridinium compounds) are known to alter FtsZ function. In this study, a series of novel quaternary pyridinium compounds was constructed based on the N-methylbenzofuro[3,2-b]quinoline and N-methylbenzoindolo[3,2-b]-quinoline derivatives and their antibacterial activity against nine significant pathogens was investigated using broth microdilution method...
April 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28425478/data-intensive-genome-level-analysis-for-identifying-novel-non-toxic-drug-targets-for-multi-drug-resistant-mycobacterium-tuberculosis
#11
Divneet Kaur, Rintu Kutum, Debasis Dash, Samir K Brahmachari
We report the construction of a novel Systems Biology based virtual drug discovery model for the prediction of non-toxic metabolic targets in Mycobacterium tuberculosis (Mtb). This is based on a data-intensive genome level analysis and the principle of conservation of the evolutionarily important genes. In the 1623 sequenced Mtb strains, 890 metabolic genes identified through a systems approach in Mtb were evaluated for non-synonymous mutations. The 33 genes showed none or one variation in the entire 1623 strains, including 1084 Russian MDR strains...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28425464/metabolic-labelling-of-the-carbohydrate-core-in-bacterial-peptidoglycan-and-its-applications
#12
Hai Liang, Kristen E DeMeester, Ching-Wen Hou, Michelle A Parent, Jeffrey L Caplan, Catherine L Grimes
Bacterial cells are surrounded by a polymer known as peptidoglycan (PG), which protects the cell from changes in osmotic pressure and small molecule insults. A component of this material, N-acetyl-muramic acid (NAM), serves as a core structural element for innate immune recognition of PG fragments. We report the synthesis of modifiable NAM carbohydrate derivatives and the installation of these building blocks into the backbone of Gram-positive and Gram-negative bacterial PG utilizing metabolic cell wall recycling and biosynthetic machineries...
April 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28425301/development-of-a-novel-rationally-designed-antibiotic-to-inhibit-a-nontraditional-bacterial-target
#13
Pavel Dibrov, Elena Dibrov, Thane G Maddaford, Melissa Kenneth, Jordan Nelson, Craig Resch, Grant N Pierce
The search for new nontraditional targets is a high priority in antibiotic design today. Bacterial membrane energetics based on sodium ion circulation offers potential alternative targets. The present work identifies the Na(+)-translocating NADH:ubiquinone oxidoreductase (Na(+)-NQR), a key respiratory enzyme in many microbial pathogens, as indispensible for the Chlamydia trachomatis infectious process. Infection by Chlamydia trachomatis significantly increased first H(+) and then Na(+) levels within the host mammalian cell...
April 20, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28424085/the-within-host-population-dynamics-of-mycobacterium-tuberculosis-vary-with-treatment-efficacy
#14
Andrej Trauner, Qingyun Liu, Laura E Via, Xin Liu, Xianglin Ruan, Lili Liang, Huimin Shi, Ying Chen, Ziling Wang, Ruixia Liang, Wei Zhang, Wang Wei, Jingcai Gao, Gang Sun, Daniela Brites, Kathleen England, Guolong Zhang, Sebastien Gagneux, Clifton E Barry, Qian Gao
BACKGROUND: Combination therapy is one of the most effective tools for limiting the emergence of drug resistance in pathogens. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We address this question by studying the population dynamics of Mycobacterium tuberculosis within tuberculosis patients undergoing treatment with different combinations of antibiotics...
April 19, 2017: Genome Biology
https://www.readbyqxmd.com/read/28421881/factors-pivotal-for-designing-of-nanoantimicrobials-an-exposition
#15
Bushra Jamil, Muhammad Imran
Understanding the interplay between bacterial pathogens and antimicrobials is a key to realize the control over infections causing morbidity and mortality. An important current issue of contemporary medicine and microbiology is the search for new strategies for adequate therapy of infectious diseases associated with rapidly emerging multidrug-resistant (MDR) pathogens. Recently, a great deal of progress has been made in the field of nanobiotechnology towards the development of various nanoantimicrobials (NAMs) as novel therapeutic solution...
April 19, 2017: Critical Reviews in Microbiology
https://www.readbyqxmd.com/read/28420878/synergistic-antimicrobial-effects-of-silver-transition-metal-combinatorial-treatments
#16
Javier A Garza-Cervantes, Arturo Chávez-Reyes, Elena C Castillo, Gerardo García-Rivas, Oscar Antonio Ortega-Rivera, Eva Salinas, Margarita Ortiz-Martínez, Sara Leticia Gómez-Flores, Jorge A Peña-Martínez, Alan Pepi-Molina, Mario T Treviño-González, Xristo Zarate, María Elena Cantú-Cárdenas, Carlos Enrique Escarcega-Gonzalez, J Rubén Morones-Ramírez
Due to the emergence of multi-drug resistant strains, development of novel antibiotics has become a critical issue. One promising approach is the use of transition metals, since they exhibit rapid and significant toxicity, at low concentrations, in prokaryotic cells. Nevertheless, one main drawback of transition metals is their toxicity in eukaryotic cells. Here, we show that the barriers to use them as therapeutic agents could be mitigated by combining them with silver. We demonstrate that synergism of combinatorial treatments (Silver/transition metals, including Zn, Co, Cd, Ni, and Cu) increases up to 8-fold their antimicrobial effect, when compared to their individual effects, against E...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420074/natural-pathogen-control-chemistry-to-replace-toxic-treatment-of-microbes-and-biofilm-in-cooling-towers
#17
REVIEW
Lon Brouse, Richard Brouse, Daniel Brouse
Application of toxic antibacterial agents is considered necessary to control prevalent fresh water microorganisms that grow in evaporative cooling water systems, but can adversely affect the environment and human health. However, natural antibacterial water chemistry has been applied in industrial cooling water systems for over 10 years to inhibit microorganisms with excellent results. The water chemistry method concentrates natural minerals in highly-softened water to produce elevated pH and dissolved solids, while maintaining low calcium and magnesium content...
March 31, 2017: Pathogens
https://www.readbyqxmd.com/read/28419231/antibiotic-resistance-in-staphylococcus-aureus-current-status-and-future-prospects
#18
Timothy J Foster
The major targets for antibiotics in staphylococci are (i) the cell envelope, (ii) the ribosome and (iii) nucleic acids. Several novel targets emerged from recent targeted drug discovery programmes including the ClpP protease and FtsZ from the cell division machinery. Resistance can either develop by horizontal transfer of resistance determinants encoded by mobile genetic elements viz plasmids, transposons and the staphylococcal cassette chromosome or by mutations in chromosomal genes. Horizontally acquired resistance can occur by one of the following mechanisms: (i) enzymatic drug modification and inactivation, (ii) enzymatic modification of the drug binding site, (iii) drug efflux, (iv) bypass mechanisms involving acquisition of a novel drug-resistant target, (v) displacement of the drug to protect the target...
April 13, 2017: FEMS Microbiology Reviews
https://www.readbyqxmd.com/read/28418235/discovery-of-the-showdomycin-gene-cluster-from-streptomyces-showdoensis-atcc-15227-yields-insight-into-the-biosynthetic-logic-of-c-nucleoside-antibiotics
#19
Kaisa Palmu, Petja Rosenqvist, Keshav Thapa, Yulia Ilina, Vilja Siitonen, Bikash Baral, Janne Mäkinen, Georgi Belogurov, Pasi Virta, Jarmo Niemi, Mikko Metsä-Ketelä
Nucleoside antibiotics are a large class of pharmaceutically relevant chemical entities, which exhibit a broad spectrum of biological activities. Most nucleosides belong to the canonical N-nucleoside family, where the heterocyclic unit is connected to the carbohydrate through a carbon-nitrogen bond. However, atypical C-nucleosides have been isolated from Streptomyces bacteria over 50 years ago, but the molecular basis for formation of these metabolites has been unknown. Here we have sequenced the genome of S...
April 18, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28417606/caboxamycin-biosynthesis-pathway-and-identification-of-novel-benzoxazoles-produced-by-cross-talk-in-streptomyces-sp-ntk-937
#20
Armando A Losada, Carolina Cano-Prieto, Raúl García-Salcedo, Alfredo F Braña, Carmen Méndez, José A Salas, Carlos Olano
Streptomyces sp. NTK937, producer of benzoxazole antibiotic caboxamycin, produces in addition a methyl ester derivative, O-methylcaboxamycin. Caboxamycin cluster, comprising one regulatory and nine structural genes, has been delimited, and each gene has been individually inactivated to demonstrate its role in the biosynthetic process. The O-methyltransferase potentially responsible for O-methylcaboxamycin synthesis would reside outside this cluster. Five of the genes, cbxR, cbxA, cbxB, cbxD and cbxE, encoding a SARP transcriptional regulator, salicylate synthase, 3-oxoacyl-ACP-synthase, ACP and amidohydrolase, respectively, have been found to be essential for caboxamycin biosynthesis...
April 18, 2017: Microbial Biotechnology
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