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https://www.readbyqxmd.com/read/28822333/virtual-screening-and-repositioning-of-inconclusive-molecules-of-beta-lactamase-bioassays-a-data-mining-approach
#1
Akshata Gad, Andrew Titus Manuel, Jinuraj K R, Lijo John, Sajeev R, Shanmuga Priya V G, Abdul Jaleel U C
This study focuses on the best possible way forward in utilizing inconclusive molecules of PubChem bioassays AID 1332, AID 434987 and AID 434955, which are related to beta-lactamase inhibitors of Mycobacterium tuberculosis (Mtb). The inadequacy in the experimental methods that were observed during the invitro screening resulted in an inconclusive dataset. This could be due to certain moieties present within the molecules. In order to reconsider such molecules, insilico methods can be suggested in place of invitro methods For instance, datamining and medicinal chemistry methods: have been adopted to prioritise the inconclusive dataset into active or inactive molecules...
July 29, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28820574/thiol-containing-metallo-%C3%AE-lactamase-inhibitors-resensitize-resistant-gram-negative-bacteria-to-meropenem
#2
Kamaleddin Haj Mohammad Ebrahim Tehrani, Nathaniel I Martin
The prevalence of infections caused by metallo-β-lactamase (MBL) expressing Gram-negative bacteria has grown at an alarming rate in recent years. Despite the fact that MBLs can deactivate virtually all β-lactams antibiotics, there are as of yet no approved drugs available that inhibit their activity. We here examine the ability of previously reported thiol-based MBL inhibitors to synergize with meropenem against a panel of Gram-negative carbapenem-resistant isolates expressing different β-lactamases. Among the compounds tested, thiomandelic acid 3 and 2-merpto-3-phenylpropionic acid 4 were found to efficiently potentiate the activity of meropenem, especially against an IMP producing strain of K...
August 18, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28820386/cost-of-nosocomial-outbreak-caused-by-ndm-1-containing-klebsiella-pneumoniae-in-the-netherlands-october-2015-january-2016
#3
Madelief Mollers, Suzanne P Lutgens, Annelot F Schoffelen, Peter M Schneeberger, Anita W M Suijkerbuijk
During October-December 2015, 29 patients in a hospital in the Netherlands acquired nosocomial infection with a multidrug-resistant, New Delhi-metallo-β-lactamase-positive Klebsiella pneumoniae strain. Extensive infection control measures were needed to stop this outbreak. The estimated economic impact of the outbreak was $804,263; highest costs were associated with hospital bed closures.
September 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28820383/carbapenemase-producing-enterobacteriaceae-and-nonfermentative-bacteria-the-philippines-2013-2016
#4
John Mark Velasco, Maria Theresa Valderama, Trent Peacock, Nirdnoy Warawadee, Kathyleen Nogrado, Fatima Claire Navarro, Domingo Chua, Srijan Apichai, Ruekit Sirigade, Louis R Macareo, Brett Swierczewski
During 2013-2016, we isolated blaNDM- and blaVIM-harboring Enterobacteriaceae and nonfermentative bacteria from patients in the Philippines. Of 130 carbapenem-resistant isolates tested, 45 were Carba NP-positive; 43 harbored blaNDM, and 2 harbored blaVIM. Multidrug-resistant microbial pathogen surveillance and antimicrobial drug stewardship are needed to prevent further spread of New Delhi metallo-β-lactamase variants.
September 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28820368/emergence-of-plasmid-mediated-fosfomycin-resistance-genes-among-escherichia-coli-isolates-france
#5
Yahia Benzerara, Salah Gallah, Baptiste Hommeril, Nathalie Genel, Dominique Decré, Martin Rottman, Guillaume Arlet
FosA, a glutathione S-transferase that inactivates fosfomycin, has been reported as the cause of enzymatic resistance to fosfomycin. We show that multiple lineages of FosA-producing extended spectrum β-lactamase Escherichia coli have circulated in France since 2012, potentially reducing the efficacy of fosfomycin in treating infections with antimicrobial drug-resistant gram-negative bacilli.
September 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28820112/prevalence-study-of-plasmid-mediated-ampc-%C3%AE-lactamases-in-enterobacteriaceae-lacking-inducible-ampc-from-saudi-hospitals
#6
Baha Abdalhamid, Samar Albunayan, Alaa Shaikh, Nasreldin Elhadi, Reem Aljindan
PURPOSE: Enterobacteriaceae encoding plasmid-mediated AmpC (pAmpC) β-lactamases confer resistance to the third generation cephalosporins. pAmpC association with extended spectrum β-lactamases (ESBLs), plasmid-mediated quinolone resistance (PMQR) and aminoglycoside modifying enzymes (AMEs) is well documented. There are limited data regarding the epidemiology and clinical significance of pAmpC in Saudi Arabia. This study aimed to determine the prevalence of pAmpC and its coexistence with ESBLs, PMQR and AMEs in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis isolates in Saudi hospitals from January to December 2015...
August 18, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28819148/analysis-and-comparative-genomics-of-r997-the-first-sxt-r391-integrative-and-conjugative-element-ice-of-the-indian-sub-continent
#7
Michael P Ryan, Patricia Armshaw, John A O'Halloran, J Tony Pembroke
The aim of this study was to analyse R997, the first integrative and conjugative element (ICE) isolated from the Indian Sub-Continent, and to determine its relationship to the SXT/R391 family of ICEs. WGS of Escherichia coli isolate AB1157 (which contains R997) was performed using Illumina sequencing technology. R997 context was assessed by de novo assembly, gene prediction and annotation tools, and compared to other SXT/R391 ICEs. R997 has a size of 85 Kb and harbours 85 ORFs. Within one of the variable regions a HMS-1 β-lactamase resistance gene is located...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818913/draft-genome-sequence-of-klebsiella-pneumoniae-704sk6-an-oxa-48-and-ctx-m-15-encoding-wastewater-isolate
#8
Roger Marti, Roger Stephan, Jochen Klumpp, Magdalena Nüesch-Inderbinen, Jörg Hummerjohann, Claudia Bagutti, Katrin Zurfluh
The Swiss wastewater isolate Klebsiella pneumoniae 704SK6, encoding OXA-48 and CTX-M-15 β-lactamases, was fully sequenced. The assembly resulted in an open chromosome of 5,208,104 bp in size (G+C content, 57.6%) and four closed plasmid sequences of 209,651, 197,670, 65,998, and 63,605 bp in size.
August 17, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28818892/draft-genome-sequences-of-two-enterobacter-cloacae-subsp-cloacae-strains-isolated-from-australian-hematology-patients-with-bacteremia
#9
Lex E X Leong, David Shaw, Lito Papanicolas, Diana Lagana, Ivan Bastian, Geraint B Rogers
Enterobacter cloacae is a common member of the gut microbiota in healthy individuals. However, it is also an opportunistic pathogen, capable of causing bacteremia. We report the draft genomes of two Enterobacter cloacae subspecies cloacae strains isolated from hematology patients with bacteremia. Both isolates carry genes encoding extended-spectrum β-lactamases.
August 17, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28818575/beta-lactam-resistance-among-haemophilus-influenzae-isolates-in-poland
#10
Marlena Kiedrowska, Alicja Kuch, Dorota Żabicka, Izabela Waśko, Patrycja Ronkiewicz, Katarzyna Wasiak, Katarzyna Bojarska, Waleria Hryniewicz, Anna Skoczyńska
OBJECTIVES: Haemophilus influenzae is a human-specific Gram-negative coccobacillus responsible for a significant number of respiratory tract infections and severe invasive infections such as meningitis and sepsis. The purpose of the study was to characterize the mechanisms of β-lactam resistance among Polish H. influenzae isolates and to evaluate the methods applied. METHODS: The study was conducted on 117 Polish H. influenzae isolates collected in 2012. Minimal inhibitory concentrations (MICs) were assessed by the broth microdilution method...
August 14, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28818544/trends-in-antimicrobial-resistance-in-bloodstream-infection-isolates-at-a-large-urban-hospital-in-malawi-1998-2016-a-surveillance-study
#11
Patrick Musicha, Jennifer E Cornick, Naor Bar-Zeev, Neil French, Clemens Masesa, Brigitte Denis, Neil Kennedy, Jane Mallewa, Melita A Gordon, Chisomo L Msefula, Robert S Heyderman, Dean B Everett, Nicholas A Feasey
BACKGROUND: Bacterial bloodstream infection is a common cause of morbidity and mortality in sub-Saharan Africa, yet few facilities are able to maintain long-term surveillance. The Malawi-Liverpool-Wellcome Trust Clinical Research Programme has done sentinel surveillance of bacteraemia since 1998. We report long-term trends in bloodstream infection and antimicrobial resistance from this surveillance. METHODS: In this surveillance study, we analysed blood cultures that were routinely taken from adult and paediatric patients with fever or suspicion of sepsis admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi from 1998 to 2016...
August 14, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28815897/multidrug-resistant-enterobacteriaceae-pseudomonas-aeruginosa-and-vancomycin-resistant-enterococci-three-major-threats-to-hematopoietic-stem-cell-transplant-recipients
#12
REVIEW
Michael J Satlin, Thomas J Walsh
Hematopoietic stem cell transplant (HSCT) recipients are uniquely threatened by the emergence of multidrug-resistant (MDR) bacteria because these patients rely on immediate active antimicrobial therapy to combat bacterial infections. This review describes the epidemiology and treatment considerations for three challenging MDR bacterial pathogens in HSCT recipients: MDR Enterobacteriaceae, including extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus (VRE)...
August 16, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28815732/antibacterial-and-%C3%AE-lactamase-inhibitory-activity-of-monocyclic-%C3%AE-lactams
#13
REVIEW
Lena Decuyper, Marko Jukič, Izidor Sosič, Aleš Žula, Matthias D'hooghe, Stanislav Gobec
Due to the widespread emergence of resistant bacterial strains, an urgent need for the development of new antibacterial agents with novel modes of action has emerged. The discovery of naturally occurring monocyclic β-lactams in the late 1970s, mainly active against aerobic Gram-negative bacteria, has introduced a new approach in the design and development of novel antibacterial β-lactam agents. The main goal was the derivatization of the azetidin-2-one core in order to improve their antibacterial potency, broaden their spectrum of activity, and enhance their β-lactamase stability...
August 16, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28812563/multicopy-plasmids-potentiate-the-evolution-of-antibiotic-resistance-in-bacteria
#14
Alvaro San Millan, Jose Antonio Escudero, Danna R Gifford, Didier Mazel, R Craig MacLean
Plasmids are thought to play a key role in bacterial evolution by acting as vehicles for horizontal gene transfer, but the role of plasmids as catalysts of gene evolution remains unexplored. We challenged populations of Escherichia coli carrying the blaTEM-1 β-lactamase gene on either the chromosome or a multicopy plasmid (19 copies per cell) with increasing concentrations of ceftazidime. The plasmid accelerated resistance evolution by increasing the rate of appearance of novel TEM-1 mutations, thereby conferring resistance to ceftazidime, and then by amplifying the effect of TEM-1 mutations due to the increased gene dosage...
November 7, 2016: Nature ecology & evolution
https://www.readbyqxmd.com/read/28811343/comparative-genomics-of-escherichia-coli-isolated-from-skin-and-soft-tissue-and-other-extraintestinal-infections
#15
Amit Ranjan, Sabiha Shaik, Nishant Nandanwar, Arif Hussain, Sumeet K Tiwari, Torsten Semmler, Savita Jadhav, Lothar H Wieler, Munirul Alam, Rita R Colwell, Niyaz Ahmed
Escherichia coli, an intestinal Gram-negative bacterium, has been shown to be associated with a variety of diseases in addition to intestinal infections, such as urinary tract infections (UTIs), meningitis in neonates, septicemia, skin and soft tissue infections (SSTIs), and colisepticemia. Thus, for nonintestinal infections, it is categorized as extraintestinal pathogenic E. coli (ExPEC). It is also an opportunistic pathogen, causing cross infections, notably as an agent of zoonotic diseases. However, comparative genomic data providing functional and genetic coordinates for ExPEC strains associated with these different types of infections have not proven conclusive...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28809565/dipicolinic-acid-derivatives-as-inhibitors-of-new-delhi-metallo-%C3%AE-lactamase-1
#16
Allie Y Chen, Pei W Thomas, Alesha C Stewart, Alexander Bergstrom, Zishuo Cheng, Callie Miller, Christopher R Bethel, Steven H Marshall, Cy V Credille, Christopher L Riley, Richard C Page, Robert A Bonomo, Michael W Crowder, David L Tierney, Walter Fast, Seth M Cohen
The efficacy of β-lactam antibiotics is threatened by the emergence and global spread of metallo-β-lactamase-(MBL) mediated resistance, specifically New Delhi-Metallo-β- lactamase-1 (NDM-1). Utilizing fragment-based drug discovery (FBDD), a new class of inhibitors for NDM-1 and two related β-lactamases, IMP-1 and VIM-2, was identified. Based on 2,6-dipicolinic acid (DPA), several libraries were synthesized for structure-activity relationship (SAR) analysis. Inhibitor 36 (IC50 = 80 nM) was identified to be highly selective for MBLs when compared to other Zn(II) metalloenzymes...
August 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28808891/nmr-backbone-resonance-assignment-of-new-delhi-metallo-beta-lactamase
#17
Chendie Yao, Qiong Wu, Guohua Xu, Conggang Li
The emerging of the New Delhi metallo-beta-lactamase (NDM-1) has become one of the greatest threats to the clinical treatment. Although the structure of NDM-1 has been determined by X-ray crystallography, the molecular mechanism and process of catalysis reaction remain elusive. NMR spectroscopy plays a unique role in the characterization of conformational dynamics. Here we report the backbone (1)H, (15)N and (13)C chemical shift assignments of NDM-1 by heteronuclear multidimensional NMR spectroscopy as well as its secondary structure in solution as predicted by TALOS+...
August 14, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28808689/role-of-ampr-in-the-high-expression-of-the-plasmid-encoded-ampc-%C3%AE-lactamase-cfe-1
#18
Ryuichi Nakano, Akiyo Nakano, Hisakazu Yano, Ryoichi Okamoto
CFE-1 is a unique plasmid-encoded AmpC β-lactamase with the regulator gene ampR. It imparts high resistance to most cephalosporins with constitutive high-level β-lactamase activity. Here, the β-lactamase activities and expression levels of ampC with or without ampR were investigated. Results suggested that the resistance of CFE-1 to cephalosporins is caused by a substitution in AmpR, in which the Asp at position 135 is modified to Ala to allow the constitutive high-level expression (derepression) of ampC...
July 2017: MSphere
https://www.readbyqxmd.com/read/28807908/activity-of-the-%C3%AE-lactamase-inhibitor-ln-1-255-against-carbapenem-hydrolyzing-class-d-%C3%AE-lactamases-from-acinetobacter-baumannii
#19
Juan Carlos Vázquez-Ucha, María Maneiro, Marta Martínez-Guitián, John Buynak, Christopher R Bethel, Robert A Bonomo, Germán Bou, Margarita Poza, Concepción González-Bello, Alejandro Beceiro
The number of infections caused by Gram-negative pathogens carrying carbapenemases is increasing, and the group of carbapenem-hydrolyzing class D β-lactamases (CHDLs) is especially problematic. Several clinically important CHDLs have been identified in A. baumannii, including OXA-23, OXA-24/40, OXA-58, OXA-143, OXA-235, and the chromosomally encoded OXA-51. The selection and dissemination of carbapenem-resistant A. baumannii strains constitutes a serious global threat. Carbapenems have been successfully utilized as last resort antibiotics for the treatment of multi-drug-resistant A...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28807759/development-of-a-highly-resolved-loop-mediated-isothermal-amplification-method-to-detect-the-n526k-ftsi-mutation-of-%C3%AE-lactamase-negative-ampicillin-resistant-haemophilus-influenzae
#20
Shinsuke Tamura, Takuya Maeda, Kazuhisa Misawa, Morichika Osa, Takaaki Hamamoto, Atsushi Yuki, Kazuo Imai, Kei Mikita, Kyoko Morichika, Akihiko Kawana, Hiroshi Matsumoto, Shigeaki Nonoyama
Rapid and easy detection of sequence polymorphisms, including nucleotide point mutations of bacterial pathogens responsible for amino acid substitutions linked to drug resistance, is essential for the proper use of antimicrobial agents. Here, a detection method using loop-mediated amplification (LAMP) combined with amplification refractory mutation system (ARMS) to accurately distinguish a different single nucleotide in the target sequence was established, named ARMS-SNP LAMP. This procedure is capable of species-specific detection of a nucleotide (1578T) in the ftsI gene on Haemophilus influenzae without amplifying the sequence carrying the point mutations (T1578G/A) in β-lactamase-negative ampicillin resistant (BLNAR) strains...
August 12, 2017: Journal of Microbiological Methods
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