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Timothy Palzkill
The most common mechanism of resistance to β-lactam antibiotics in Gram-negative bacteria is the production of β-lactamases that hydrolyze the drugs. Class A β-lactamases are serine active-site hydrolases that include the common TEM, CTX-M, and KPC enzymes. The TEM enzymes readily hydrolyze penicillins and older cephalosporins. Oxyimino-cephalosporins, such as cefotaxime and ceftazidime, however, are poor substrates for TEM-1 and were introduced, in part, to circumvent β-lactamase-mediated resistance. Nevertheless, the use of these antibiotics has lead to evolution of numerous variants of TEM with mutations that significantly increase the hydrolysis of the newer cephalosporins...
2018: Frontiers in Molecular Biosciences
María Araque, Indira Labrador
Objectives: Antimicrobial resistant extended-spectrum-β-lactamase-producing Enterobacteriaceae (ESBL-PE) have been shown to be present in healthy communities. This study examined healthy children from the rural Andean village of Llano del Hato, Mérida, Venezuela, who have had little or no antibiotic exposure to determine the prevalence of fecal carriage of ESBL-producing Escherichia coli (ESBL-EC). Methods: A total of 78 fecal samples were collected in healthy children aged from 1 to 5 years...
January 2018: Osong Public Health and Research Perspectives
Zhu-Jun Yu, Sha Liu, Shu Zhou, Hui Li, Fan Yang, Ling-Ling Yang, Yong Wu, Li Guo, Guo-Bo Li
Rosmarinic acid (RA), a polyphenolic phytochemical, has broad-spectrum biological and pharmacological activity. A virtual target screening method termed IFPTarget combined with enzyme inhibition assays led to the identification of the clinically relevant metallo-β-lactamase (MBL) VIM-2 as one of unexploited targets of RA. The enzyme kinetic studies indicated that RA is a fully reversible, substrate-competitive VIM-2 inhibitor. The isothermal titration calorimetry (ITC) analyses revealed that the initial binding of RA to VIM-2 is mainly due to enthalpy contribution...
February 14, 2018: Bioorganic & Medicinal Chemistry Letters
Fang Chen, Ling Wang, Min Wang, Yixin Xie, Xiaomeng Xia, Xianping Li, Yanhua Liu, Wei Cao, Tingting Zhang, Pengling Li, Min Yang
The present study aimed to develop a rational therapy based on the genetic epidemiology, molecular mechanism evaluation and in vitro antibiotic combinations activity in multidrug-resistant Acinetobacter baumannii (MDRAB). MDRAB was screened by the Kirby-Bauer method. The random amplified polymorphic DNA technique was used to establish genetic fingerprinting, and a series of resistance genes were detected by polymerase chain reaction. Antimicrobial agents including amikacin (AK), cefoperazone/sulbactam (SCF I/II), meropenem (MEM), minocycline (MINO) and ciprofloxacin (CIP) were used to determine the minimum inhibitory concentrations (MICs) and interactions between antibiotics by the broth microdilution method and chequerboard assays...
February 2018: Oncology Letters
Masomeh Dehshiri, Seyed Sajjad Khoramrooz, Mohammad Zoladl, Seyed Abdolmajid Khosravani, Najmeh Parhizgari, Mohammad Hossein Motazedian, Soheyla Jahedi, Asghar Sharifi
BACKGROUND: The extended- spectrum β-lactamase producing bacteria are widely spread worldwide. The productions of these enzymes cause bacterial resistance to a wide range of antibiotics. The aim of this study was to investigated the frequency of K. pneumonia encoding genes for CTX-M, TEM-1 and SHV-1 extended-spectrum beta lactamases enzymes isolated from urinary tract infection. METHODS: This study is cross-sectional study. All K. pneumonia isolates from urine samples, which had grown on media culture more than 105 were delivered to the medical microbiology laboratory...
February 13, 2018: Annals of Clinical Microbiology and Antimicrobials
Vitaly Grigorenko, Igor Uporov, Maya Rubtsova, Irina Andreeva, Dmitrii Shcherbinin, Alexander Veselovsky, Oksana Serova, Maria Ulyashova, Igor Ishtubaev, Alexey Egorov
Highly mutable β-lactamases are responsible for the ability of Gram-negative bacteria to resist β-lactam antibiotics. Using site-directed mutagenesis technique, we have produced in vitro a number of recombinant analogs of naturally occurring TEM-type β-lactamases, bearing the secondary substitution Q39K and key mutations related to the extended-spectrum (E104K, R164S) and inhibitor-resistant (M69V) β-lactamases. The mutation Q39K alone was found to be neutral and hardly affected the catalytic properties of β-lactamases...
January 2018: FEBS Open Bio
Lei Han, Jine Lei, Jiru Xu, Shaoshan Han
Acinetobacter baumannii is one of the major threats in clinical infections due to its antibiotic resistance ability. It shows increasing resistance to carbapenems, mainly due to β-lactamase mediated mechanisms. The aim of this study was to investigate carbapenem resistance (CR) profiles and analyze β-lactamases genes composition of clinical A. baumannii strains from a teaching hospital in Xi'an. The resistance patterns to imipenem and meropenem were checked for 51 clinical A. baumannii strains. The existence of 15 β-lactamases genes was detected by polymerase chain reaction (PCR), and the positive genes were sequenced...
December 2017: Medicine (Baltimore)
María Díez-Aguilar, María-Carmen Conejo, María-Isabel Morosini, Núria Tormo Palop, Concepción Gimeno, Rafael Cantón, Álvaro Pascual
A nationwide study was developed to evaluate the ability of 60 Spanish clinical microbiology laboratories to predict the underlying β-lactam resistance mechanisms of 12 Enterobacteriaceae strains (CCS01-CCS12). Results obtained by two reference laboratories were compared with those reported by the participants that used their own routine susceptibility testing methodology. CLSI interpretive criteria were used in 53.3% of the centres, while 46.7% used EUCAST. The overall categorical agreement (CA) was 85.5%...
December 21, 2017: International Journal of Antimicrobial Agents
Tiphaine Cecchini, Eun-Jeong Yoon, Yannick Charretier, Chloé Bardet, Corinne Beaulieu, Xavier Lacoux, Jean-Denis Docquier, Jerome Lemoine, Patrice Courvalin, Catherine Grillot-Courvalin, Jean-Philippe Charrier
Resistance to β-lactams in Acinetobacter baumannii involves various mechanisms. To decipher them, whole genome sequencing (WGS) and real-time quantitative polymerase chain reaction (RT-qPCR) were complemented by mass spectrometry (MS) in selected reaction monitoring mode (SRM) in 39 clinical isolates. The targeted label-free proteomic approach enabled, in one hour and using a single method, the quantitative detection of 16 proteins associated with antibiotic resistance: eight acquired β-lactamases (i.e. GES, NDM-1, OXA-23, OXA-24, OXA-58, PER, TEM-1 and VEB), two resident β-lactamases (i...
December 19, 2017: Molecular & Cellular Proteomics: MCP
Su Wang, Shu-Zhen Xiao, Fei-Fei Gu, Jin Tang, Xiao-Kui Guo, Yu-Xing Ni, Jie-Ming Qu, Li-Zhong Han
BACKGROUND: Enterobacter cloacae is a major nosocomial pathogen causing bloodstream infections. We retrospectively conducted a study to assess antimicrobial susceptibility and phylogenetic relationships of E. cloacae bloodstream isolates in two tertiary university-affiliated hospitals in Shanghai, in order to facilitate managements of E. cloacae bloodstream infections and highlight some unknowns for future prevention. METHODS: Fifty-three non-duplicate E. cloacae bloodstream isolates were consecutively collected from 2013 to 2016...
2017: PloS One
Sima Tokajian, Rima Moghnieh, Tamara Salloum, Harout Arabaghian, Sahar Alousi, Jennifer Moussa, Edmond Abboud, Souad Youssef, Rola Husni
AIM: To evaluate the effects of population influx of refugees on the prevalence of extended-spectrum β-lactamase-producing Escherichia coli in wastewater networks in Lebanon. MATERIALS & METHODS: Pulsed-field gel electrophoresis, multilocus sequence typing and antibiotic resistance genes typing were performed. RESULTS: 53.1% of isolates recovered from Al-Qaa refugee camp were positive for the tested resistant determinants compared with 49...
January 2018: Future Microbiology
Selma Uzunović, Amir Ibrahimagić, Branka Bedenić
Aim To investigate the prevalence of derepressed/partly derepressed/inducible and ESBL/AmpC-producing Enterobacter cloacae isolates and treatment options for infections associated with those isolates. Methods Antibiotic susceptibility was determined by disc diffusion and broth microdilution according to CLSI guidelines. Doubledisk synergy test (DDST) was performed in order to screen for ESBLs and combined disk test with phenylboronic acid to detect AmpC β -lactamases. PCR was used to detect blaESBL/blacarb genes...
February 1, 2018: Medicinski Glasnik
Alicia Tran-Dien, Simon Le Hello, Christiane Bouchier, François-Xavier Weill
BACKGROUND: Ampicillin, the first semi-synthetic penicillin active against Enterobacteriaceae, was released onto the market in 1961. The first outbreaks of disease caused by ampicillin-resistant strains of Salmonella enterica serotype Typhimurium were identified in the UK in 1962 and 1964. We aimed to date the emergence of this resistance in historical isolates of S enterica serotype Typhimurium. METHODS: In this retrospective, whole-genome sequencing study, we analysed 288 S enterica serotype Typhimurium isolates collected between 1911 and 1969 from 31 countries on four continents and from various sources including human beings, animals, feed, and food...
February 2018: Lancet Infectious Diseases
Lingwei Meng, Xiangkun Li, Xinran Wang, Kaili Ma, Gaige Liu, Jie Zhang
This study aimed to reveal how amoxicillin (AMX) affected the microbial community and the spread mechanism of antibiotic resistance genes (ARGs) in the AMX manufacture wastewater treatment system. For this purpose, a 1.47 L expanded granular sludge bed (EGSB) reactor was designed and run for 241days treating artificial AMX manufacture wastewater. 454 pyrosequencing was applied to analyze functional microorganisms in the system. The antibiotic genes OXA-1 , OXA-2 , OXA-10 , TEM-1 , CTX-M-1 , class I integrons (intI1) and 16S rRNA genes were also examined in sludge samples...
November 2017: Journal of Environmental Sciences (China)
Muhammad Attiq Rehman, Xianhua Yin, Dion Lepp, Chad Laing, Kim Ziebell, Guylaine Talbot, Edward Topp, Moussa Sory Diarra
The production of extended-spectrum β-lactamases (ESBLs) conferring resistance to new derivatives of β-lactams is a major public health threat if present in pathogenic Gram-negative bacteria. The objective of this study was to characterize ceftiofur (TIO)- or cefotaxime (FOX)-resistant Escherichia coli isolated from dairy cow manure. Twenty-four manure samples were collected from four farms and incubated under anaerobic conditions for 20 weeks at 4 °C or at 25 °C. A total of 37 TIO- or FOX-resistant E. coli were isolated from two of the four farms to determine their susceptibility to 14 antibiotics...
November 17, 2017: Veterinary Sciences
X-J Ma, X-F Chen, W-L Chen, R Chen, J Huang, X-D Luo, J-Y Liao, X-P Chen
OBJECTIVE: To study the alteration of CD8+ memory T cell subsets under different immune statuses during the spontaneous clearance of hepatitis B virus (HBV) in Chinese patients with chronic HBV infection. PATIENTS AND METHODS: We analyzed Chinese patients with chronic HBV infection including 10 patients with Hepatitis B surface Antigen (HBsAg) spontaneous seroconversion, 25 patients with Hepatitis B virus e Antigen (HBeAg) spontaneous seroconversion, 25 patients with chronic hepatitis B (CHB), and 25 chronic HBV carriers...
October 2017: European Review for Medical and Pharmacological Sciences
Michael J Rennie, Mark L Watsford, Robert W Spurrs, Stephen J Kelly, Matthew J Pine
OBJECTIVES: To examine the frequency and time spent in the phases of Australian Football (AF) match-play and to assess the intra-assessor reliability of coding these phases of match-play. DESIGN: Observational, intra-reliability assessment. METHODS: Video footage of 10 random quarters of AF match-play were coded by a single researcher. Phases of offence, defence, contested play, umpire stoppage, set shot and goal reset were coded using a set of operational definitions...
October 23, 2017: Journal of Science and Medicine in Sport
Vera Manageiro, David Félix, Daniela Jones-Dias, Daniel A Sampaio, Luís Vieira, Luísa Sancho, Eugénia Ferreira, Manuela Caniça
A new QepA4 variant was detected in an O86:H28 ST156-fimH38 Escherichia coli, showing a multidrug-resistance phenotype. PAβN inhibition of qepA4-harboring transconjugant resulted in increase of nalidixic acid accumulation. The qepA4 and catA1 genes were clustered in a 26.0-kp contig matching an IncF-type plasmid, and containing a Tn21-type transposon with multiple mobile genetic elements. This QepA variant is worrisome because these determinants might facilitate the selection of higher-level resistance mutants, playing a role in the development of resistance, and/or confer higher-level resistance to fluoroquinolones in association with chromosomal mutations...
2017: Frontiers in Microbiology
P Boonyalekha, A Meechai, C Tayapiwatana, K Kitidee, D Waraho-Zhmayev
Protease inhibitors (PIs) have been used to treat various types of symptoms or diseases. However, current PIs block the protease activity by targeting the protease active site which has been shown to be sensitive to the off-target effect due to crossreactivity with protease homologues. An alternative approach to inhibiting protease activity is to target the substrate, specifically by blocking the substrate cleavage site. We propose to employ synthetic biology approach to create a synthetic E. coli to be used as a protease inhibitor detecting biomachine that can effectively isolate intrabodies, a new generation of protease inhibitor drug...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
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