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OmpK36

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https://www.readbyqxmd.com/read/29782237/effect-of-porins-and-bla-kpc-expression-on-activity-of-imipenem-with-relebactam-in-klebsiella-pneumoniae-can-antibiotic-combinations-overcome-resistance
#1
Gregory Balabanian, Michael Rose, Nyla Manning, David Landman, John Quale
Imipenem with relebactam is a novel β-lactam-β-lactamase inhibitor that has activity against most KPC-producing Enterobacteriaceae. Using 10 isolates of KPC-possessing Klebsiella pneumoniae, we assessed the relationship between imipenem-relebactam minimum inhibitory concentrations (MICs) and mechanisms known to contribute to antimicrobial resistance. The effect of adding a second agent was assessed by time-kill experiments. Mutations affecting the genes encoding porins ompK35 and ompK36 and identification of β-lactamases were assessed by PCR...
May 21, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/29735827/molecular-characterisation-for-clonality-and-transmission-dynamics-of-an-outbreak-of-klebsiella-pneumoniae-amongst-neonates-in-a-tertiary-care-centre-in-south-india
#2
Chaitra Shankar, Manish Kumar, Ashtawarthani Baskaran, Miracle Magdelene Paul, Nithya Ponmudi, Sridhar Santhanam, Joy Sarojini Michael, Balaji Veeraraghavan
Purpose: Sepsis is a significant cause of morbidity and mortality amongst neonates. Klebsiella pneumoniae is a common cause of nosocomial outbreaks causing bacteraemia and having potential of acquiring plasmids enhancing antimicrobial resistance. In the present study, we investigate K. pneumoniae outbreak causing bacteraemia amongst neonates over a span of 2 months. Isolates were characterised for antimicrobial resistance, virulence, molecular typing for clonality and plasmid typing for transmission dynamics, and patient outcome was investigated...
January 2018: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29708041/comparative-analysis-of-klebsiella-pneumoniae-strains-isolated-in-2012-2016-that-differ-by-antibiotic-resistance-genes-and-virulence-genes-profiles
#3
Anastasia I Lev, Eugeny I Astashkin, Angelina A Kislichkina, Ekaterina V Solovieva, Tatiana I Kombarova, Olga V Korobova, Olga N Ershova, Irina A Alexandrova, Vladimir E Malikov, Alexander G Bogun, Alexander I Borzilov, Nikolay V Volozhantsev, Edward A Svetoch, Nadezhda K Fursova
The antibacterial resistance and virulence genotypes and phenotypes of 148 non-duplicate Klebsiella pneumoniae strains collected from 112 patients in Moscow hospitals in 2012-2016 including isolates from the respiratory system (57%), urine (30%), wounds (5%), cerebrospinal fluid (4%), blood (3%), and rectal swab (1%) were determined. The majority (98%) were multidrug resistant (MDR) strains carrying blaSHV (91%), blaCTX-M (74%), blaTEM (51%), blaOXA (38%), and blaNDM (1%) beta-lactamase genes, class 1 integrons (38%), and the porin protein gene ompK36 (96%)...
April 30, 2018: Pathogens and Global Health
https://www.readbyqxmd.com/read/29657865/stress-adaptive-responses-associated-with-high-level-carbapenem-resistance-in-kpc-producing-klebsiella-pneumoniae
#4
Sheila Adams-Sapper, Adam Gayoso, Lee W Riley
Carbapenem-resistant Enterobacteriaceae (CRE) organisms have emerged to become a major global public health threat among antimicrobial resistant bacterial human pathogens. Little is known about how CREs emerge. One characteristic phenotype of CREs is heteroresistance, which is clinically associated with treatment failure in patients given a carbapenem. Through in vitro whole-transcriptome analysis we tracked gene expression over time in two different strains (BR7, BR21) of heteroresistant KPC-producing Klebsiella pneumoniae, first exposed to a bactericidal concentration of imipenem followed by growth in drug-free medium...
2018: Journal of Pathogens
https://www.readbyqxmd.com/read/29626658/immunization-with-the-outer-membrane-proteins-ompk17-and-ompk36-elicits-protection-against-klebsiella-pneumoniae-in-the-murine-infection-model
#5
Kawther E Hussein, Mohammed Bahey-El-Din, Salah A Sheweita
Klebsiella pneumoniae is a Gram-negative bacterium that is increasingly reported as a serious nosocomial and community-acquired pathogen. In the current study, two K. pneumoniae antigens, OmpK17 and OmpK36, as well as their fusion protein cognate F36/17 were investigated as potential vaccine candidates in a murine infection model. Three immunoadjuvants, namely the Gram-positive Enhancer Matrix (GEM) adjuvant, synthetic hemozoin (Hz) adjuvant and incomplete Freund's adjuvant (IFA) were evaluated. Genes of OmpK17 and OmpK36 antigens as well as their fusion protein were cloned in Escherichia coli for recombinant expression...
April 4, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29621592/role-of-association-of-ompk35-and-ompk36-alteration-and-bla-esbl-and-or-bla-ampc-in-conferring-carbapenem-resistance-among-non-producing-carbapenemase-klebsiella-pneumoniae
#6
Zaineb Hamzaoui, Alain Ocampo-Sosa, Marta Fernandez Martinez, Sarrah Landolsi, Sana Ferjani, Elaa Maamar, Mabrouka Saidani, Amine Slim, Luis Martinez-Martinez, Ilhem Boutiba-Ben Boubaker
In K. pneumoniae, the loss of the two major outer membrane porins (OMPs) OmpK35 and OmpK36 confers resistance to carbapenem in strains producing extended spectrum β-lactamases or plasmid-mediated AmpC-type β-lactamases. At Charles Nicolle hospital of Tunis, all carbapenem-resistant Enterobacteriaceae (CRE) were collected over a 6-year period. The aim of this work was to investigate the mechanisms responsible for carbapenem resistance in non-carbapenemase-producing K. pneumoniae (NCPK) strains. Among the 334 CRE collected strains between 2010 and 2015, 44 (13...
April 2, 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29458684/global-survey-of-klebsiella-pneumoniae-major-porins-from-ertapenem-non-susceptible-isolates-lacking-carbapenemases
#7
Mark G Wise, Elizabeth Horvath, Katherine Young, Daniel F Sahm, Krystyna M Kazmierczak
PURPOSE: To understand the diversity of porin disruption in Klebsiella pneumoniae, the major outer membrane protein (OMP) porins, OmpK35 and OmpK36, were examined in a set of isolates that did not harbour traditional carbapenem-hydrolysing enzymes, but nevertheless tested non-susceptible to ertapenem. METHODS: A world-wide collection of Klebsiella pneumoniae isolates that were part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance project over the years 2008-2014 were characterised with regard to their β-lactamase gene carriage and potential permeability defects...
March 2018: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29399114/mechanism-for-carbapenem-resistance-of-clinical-enterobacteriaceae-isolates
#8
Yafei Ye, Lijuan Xu, Yanping Han, Zhe Chen, Cailin Liu, Liang Ming
Carbapenemase-producing 'super bacteria', particularly NDM-1 and its variants, have become a major public health concern worldwide. The present study aimed to explore the molecular mechanism for carbapenem resistance of clinical Enterobacteriaceae isolates. Seventy-eight non-repeated Enterobacteriaceae strains resistant to any carbapenem were screened at the First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) between December 2011 and December 2015. Outer membrane porin (OMP) proteins were detected using SDS-PAGE...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29373087/an-outbreak-of-ndm-1-producing-klebsiella-pneumoniae-associated-with-ompk35-and-ompk36-porin-loss-in-tunisia
#9
Zaineb Hamzaoui, Alain Ocampo-Sosa, Elaa Maamar, Marta Fernandez Martinez, Sana Ferjani, Samia Hammami, Sarra Harbaoui, Nathalie Genel, Guillaume Arlet, Mabrouka Saidani, Amine Slim, Ilhem Boutiba-Ben Boubaker, Luis Martinez-Martinez
OBJECTIVES: To describe clinical and molecular characteristics of an outbreak due to metallo-β-lactamases (MBLs) producing Klebsiella pneumoniae collected at Charles Nicolle Hospital of Tunis and to analyze the impact of outer membrane porin (OMP) loss on carbapenem resistance levels. METHODS: Between 2010 and 2015, 178 carbapenem-resistant Enterobacteriaceae were isolated. Screening for MBL production was performed using combined disk diffusion method, with imipenem and ethylene diamine tetraacetic acid (EDTA) as inhibitors...
January 26, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/29275225/the-efflux-pump-inhibitor-phenylalanine-arginine-%C3%AE-naphthylamide-pa%C3%AE-n-increases-resistance-to-carbapenems-in-chilean-clinical-isolates-of-kpc-producing-klebsiella-pneumoniae
#10
Alejandra Vera-Leiva, Sergio Carrasco-Anabalón, Celia A Lima, Nicolás Villagra, Mariana Domínguez, Helia Bello-Toledo, Gerardo González-Rocha
OBJECTIVES: KPC-producing strains present a wide range of carbapenem minimum inhibitory concentrations (MICs). This variation may be due to differential expression of blaKPC and porin genes, efflux pump activity and the production of extended-spectrum β-lactamases and/or AmpC β-lactamases. The aim of this study was to determine the role of efflux pumps inhibited by phenylalanine-arginine β-naphthylamide (PAβN) in resistance to carbapenems in Chilean clinical isolates of blaKPC -harbouring Klebsiella pneumoniae...
March 2018: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29232167/tigecycline-susceptibility-of-klebsiella-pneumoniae-complex-and-escherichia-coli-isolates-from-companion-animals-the-prevalence-of-tigecycline-nonsusceptible-k-pneumoniae-complex-including-internationally-expanding-human-pathogenic-lineages
#11
Toyotaka Sato, Kazuki Harada, Masaru Usui, Yuzo Tsuyuki, Tsukasa Shiraishi, Yutaka Tamura, Shin-Ichi Yokota
Transmission of tigecycline-nonsusceptible pathogenic Enterobacteriaceae from companion animals to human should be a concern because tigecycline is a last-line drug for treating multidrug-resistant Enterobacteriaceae in human medicine. However, tigecycline susceptibility of Enterobacteriaceae isolated from companion animals has not been investigated. In this study, we investigated the tigecycline susceptibility of Klebsiella pneumoniae complex and Escherichia coli isolates from dogs and cats, and evaluated their human pathogenicity potential...
December 12, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/29230684/imipenem-relebactam-and-meropenem-vaborbactam-two-novel-carbapenem-%C3%AE-lactamase-inhibitor-combinations
#12
REVIEW
George G Zhanel, Courtney K Lawrence, Heather Adam, Frank Schweizer, Sheryl Zelenitsky, Michael Zhanel, Philippe R S Lagacé-Wiens, Andrew Walkty, Andrew Denisuik, Alyssa Golden, Alfred S Gin, Daryl J Hoban, Joseph P Lynch, James A Karlowsky
Relebactam (formerly known as MK-7655) is a non-β-lactam, bicyclic diazabicyclooctane, β-lactamase inhibitor that is structurally related to avibactam, differing by the addition of a piperidine ring to the 2-position carbonyl group. Vaborbactam (formerly known as RPX7009) is a non-β-lactam, cyclic, boronic acid-based, β-lactamase inhibitor. The structure of vaborbactam is unlike any other currently marketed β-lactamase inhibitor. Both inhibitors display activity against Ambler class A [including extended-spectrum β-lactamases (ESBLs), Klebsiella pneumoniae carbapenemases (KPCs)] and class C β-lactamases (AmpC)...
January 2018: Drugs
https://www.readbyqxmd.com/read/29156685/whole-genome-and-transcriptome-analysis-reveal-maldi-tof-ms-and-sds-page-have-limited-performance-for-the-detection-of-the-key-outer-membrane-protein-in-carbapenem-resistant-klebsiella-pneumoniae-isolates
#13
Naina Adren Pinto, Roshan D'Souza, In Sik Hwang, Jongrak Choi, Yong Ha In, Hyung Soon Park, Choong-Min Ryu, Dongeun Yong, Kyungwon Lee
To detect the outer membrane protein (OMP), which plays a key role in carbapenem resistance, whole-genome and transcriptome analysis of the clinical carbapenem-resistant Klebsiella pneumoniae was carried out. The index strain lacked both OmpK35 and OmpK36, whereas the other strains lacked only OmpK35. After SDS-PAGE, the putative OMP bands were excised and identified as OmpA and OmpK36. MALDI-TOF MS showed peaks at ∼36 and ∼38 kDa that corresponded to OmpA and OmpK36, respectively. In all the strains except YMC2014/03/P345, the ∼38 kDa peaks were present...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29038260/meropenem-vaborbactam-resistance-selection-resistance-prevention-and-molecular-mechanisms-in-mutants-of-kpc-producing-klebsiella-pneumoniae
#14
Dongxu Sun, Debora Rubio-Aparicio, Kirk Nelson, Michael N Dudley, Olga Lomovskaya
Vaborbactam (formerly RPX7009) is a new β-lactamase inhibitor based on a cyclic boronic acid pharmacophore with potent inhibitory activity against <u>K</u>lebsiella <u>p</u>neumoniae <u>c</u>arbapenemases (KPC). It has been developed in combination with meropenem. The objective of these studies was to identify the concentrations of both agents associated with the selection or prevention of single-step mutations leading to reduced sensitivity to the combination and to characterize the selected mutations...
December 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28979250/evaluation-of-recombinant-multi-epitope-outer-membrane-protein-based-klebsiella-pneumoniae-subunit-vaccine-in-mouse-model
#15
Litty Babu, Siva R Uppalapati, Murali H Sripathy, Prakash N Reddy
Safety and protective efficacy of recombinant multi-epitope subunit vaccine (r-AK36) was evaluated in a mouse model. Recombinant AK36 protein comprised of immunodominant antigens from outer membrane proteins (Omp's) of Klebsiella pneumoniae namely OmpA and OmpK36. r-AK36 was highly immunogenic and the hyperimmune sera reacted strongly with native OmpA and OmpK36 proteins from different K. pneumoniae strains. Hyperimmune sera showed cross-reactivity with Omp's of other Gram-negative organisms. Humoral responses showed a Th2-type polarized immune response with IgG1 being the predominant antibody isotype...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28932329/molecular-characterization-of-klebsiella-pneumoniae-clinical-isolates-with-elevated-resistance-to-carbapenems
#16
Rasha Barwa, Mona Shaaban
BACKGROUND: Emergence of carbapenems-resistant K. pneumoniae represents a serious challenge for antimicrobial therapy. OBJECTIVE: The aim of this research is to determine different mechanisms mediating the emergence of K. pneumoniae isolates with high-level carbapenem resistance. METHOD: A total of 80 K. pneumoniae isolates were purified from sputum and urine specimens. The minimum inhibitory concentrations (MICs) of imipenem and meropenem were determined by broth microdilution method...
2017: Open Microbiology Journal
https://www.readbyqxmd.com/read/28739787/resistance-to-ceftazidime-avibactam-is-due-to-transposition-of-kpc-in-a-porin-deficient-strain-of-klebsiella-pneumoniae-with-increased-efflux-activity
#17
Kirk Nelson, Peera Hemarajata, Dongxu Sun, Debora Rubio-Aparicio, Ruslan Tsivkovski, Shangxin Yang, Robert Sebra, Andrew Kasarskis, Hoan Nguyen, Blake M Hanson, Shana Leopold, George Weinstock, Olga Lomovskaya, Romney M Humphries
Ceftazidime-avibactam is an antibiotic with activity against serine beta-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). Recently, reports have emerged of KPC-producing isolates resistant to this antibiotic, including a report of a wild-type KPC-3 producing sequence type 258 Klebsiella pneumoniae that was resistant to ceftazidime-avibactam. We describe a detailed analysis of this isolate, in the context of two other closely related KPC-3 producing isolates, recovered from the same patient. Both isolates encoded a nonfunctional OmpK35, whereas we demonstrate that a novel T333N mutation in OmpK36, present in the ceftazidime-avibactam resistant isolate, reduced the activity of this porin and impacted ceftazidime-avibactam susceptibility...
October 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28731269/biofilm-formation-and-antibiotic-resistance-in-klebsiella-pneumoniae-urinary-strains
#18
C Vuotto, F Longo, C Pascolini, G Donelli, M P Balice, M F Libori, V Tiracchia, A Salvia, P E Varaldo
AIMS: Multidrug-resistant Klebsiella pneumoniae has become a relevant healthcare-associated pathogen. Capsule, type 1 and 3 fimbriae (mrkA gene), type 2 quorum-sensing system (luxS), synthesis of D-galactan I (wbbM), LPS transport (wzm) and poly-beta-1,6-N-acetyl-D-glucosamine (pgaA) seem involved in K. pneumoniae biofilm. Nonenzymatic antibiotic resistance is related to nonexpression or mutation of porins (OmpK35 and OmpK36), and efflux pump (acrB) overexpression. The aim of this study was to analyse some virulence factors of K...
July 21, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28713357/extensively-drug-resistant-klebsiella-pneumoniae-causing-nosocomial-bloodstream-infections-in-china-molecular-investigation-of-antibiotic-resistance-determinants-informing-therapy-and-clinical-outcomes
#19
Wenzi Bi, Haiyang Liu, Rhys A Dunstan, Bin Li, Von Vergel L Torres, Jianming Cao, Lijiang Chen, Jonathan J Wilksch, Richard A Strugnell, Trevor Lithgow, Tieli Zhou
The rise in diversity of antimicrobial resistance phenotypes seen in Klebsiella pneumoniae is becoming a serious antibiotic management problem. We sought to investigate the molecular characteristics and clinical implications of extensively drug-resistant (XDR) K. pneumoniae isolated from different nosocomial bloodstream infections (BSIs) patients from July 2013 to November 2015. Even in combination treatment, meropenem did not protect against mortality of BSIs patients (P = 0.015). In contrast, tigecycline in combination with other antimicrobial agents significantly protected against mortality (P = 0...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28708586/whole-genome-and-transcriptome-analysis-reveal-maldi-tof-ms-and-sds-page-have-limited-performance-for-the-detection-of-the-key-outer-membrane-protein-in-carbapenem-resistant-klebsiella-pneumoniae-isolates
#20
Naina Adren Pinto, Roshan D'Souza, In Sik Hwang, Jongrak Choi, Yong Ha In, Hyung Soon Park, Choong-Min Ryu, Dongeun Yong, Kyungwon Lee
To detect the outer membrane protein (OMP), which plays a key role in carbapenem resistance, whole-genome and transcriptome analysis of the clinical carbapenem-resistant Klebsiella pneumoniae was carried out. The index strain lacked both OmpK35 and OmpK36, whereas the other strains lacked only OmpK35. After SDS-PAGE, the putative OMP bands were excised and identified as OmpA and OmpK36. MALDI-TOF MS showed peaks at ~36 and ~38 kDa that corresponded to OmpA and OmpK36, respectively. In all the strains except YMC2014/03/P345, the ~38 kDa peaks were present...
July 5, 2017: Oncotarget
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