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https://www.readbyqxmd.com/read/28316602/toll-like-receptor-ligand-based-vaccine-adjuvants-require-intact-myd88-signaling-in-antigen-presenting-cells-for-germinal-center-formation-and-antibody-production
#1
Munir M Mosaheb, Michael L Reiser, Lee M Wetzler
Vaccines are critical in the fight against infectious diseases, and immune-stimulating adjuvants are essential for enhancing vaccine efficacy. However, the precise mechanisms of action of most adjuvants are unknown. There is an urgent need for customized and adjuvant formulated vaccines against immune evading pathogens that remain a risk today. Understanding the specific role of various cell types in adjuvant-induced protective immune responses is vital for an effective vaccine design. We have investigated the role of cell-specific MyD88 signaling in vaccine adjuvant activity in vivo, using Neisserial porin B (PorB), a TLR2 ligand-based adjuvant, compared with an endosomal TLR9 ligand (CpG) and toll-like receptor (TLR)-independent (alum, MF59) adjuvants...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28315387/functional-role-of-ompf-and-ompc-porins-in-pathogenesis-of-avian-pathogenic-escherichia-coli
#2
Hassan M A Hejair, Yingchu Zhu, Jiale Ma, Yue Zhang, Zihao Pan, Wei Zhang, Huochun Yao
Avian pathogenic Escherichia coli is an important pathogen causes systemic infections in avian species and large economic losses in poultry industry worldwide. The functional role of porins during the infection and their mechanisms of interaction with host tissues for adhesion to and invasion are poorly understood. However, whether porins play a role in infection remains unclear. In this study we evaluated the potential of ompF and ompC outer membrane porins in the pathogenesis of avian pathogenic E. coli (APEC) strain TW-XM...
March 14, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28303836/carbapenem-nonsusceptibility-with-modified-oprd-in-clinical-isolates-of-pseudomonas-aeruginosa-from-india
#3
Debarati Choudhury, Anupam Das Talukdar, Manabendra Dutta Choudhury, Anand Prakash Maurya, Debadatta Dhar Chanda, Atanu Chakravorty, Amitabha Bhattacharjee
This study was undertaken to investigate OprD porin-mediated carbapenem nonsusceptibility in clinical isolates of Pseudomonas aeruginosa from a tertiary referral hospital of Northeast India. A total of 267 nonduplicate, consecutive clinical isolates of P. aeruginosa were obtained. Mutation and expression levels of OprD gene were determined in carbapenem-nonsusceptible carbapenemase-nonproducing isolates. Among 19 carbapenem-nonsusceptible carbapenemase-nonproducing isolates, 11 of them demonstrated variable band pattern while performing denaturing gradient gel electrophoresis with amplified products of OprD gene...
January 2017: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28291784/comparative-genome-analyses-of-mycobacteria-give-better-insights-into-their-evolution
#4
Wei Yee Wee, Avirup Dutta, Siew Woh Choo
Mycobacteria a genus of Actinobacteria are widespread in nature ranging from soil-dwelling saprophytes to human and animal pathogens. The rate of growth has been a classifying factor for the Mycobacterium spp., dividing them into the rapid growers and the slow growers. Here we have performed a comparative genome study of mycobacterial species in order to get better understanding of their evolution, particularly to understand the distinction between the rapid and slow growers. Our study shows that the slow growers had generally gained and lost more genes compared to the rapid growers...
2017: PloS One
https://www.readbyqxmd.com/read/28291698/detection-and-analysis-of-different-interactions-between-resistance-mechanisms-and-carbapenems-in-clinical-isolates-of-klebsiella-pneumoniae
#5
Tanise Vendruscolo Dalmolin, Bianca Vendruscolo Bianchini, Grazielle Guidolin Rossi, Ana Carolina Ramos, Ana Cristina Gales, Priscila de Arruda Trindade, Marli Matiko Anraku de Campos
Carbapenems are considered last-line agents for the treatment of serious infections caused by Klebsiella pneumoniae, and this microorganism may exhibit resistance to β-lactam antibiotics due to different mechanisms of resistance. We evaluated 27 isolates of K. pneumoniae resistant to carbapenems recovered from inpatients at the University Hospital of Santa Maria-RS from July 2013 to August 2014. We carried out antimicrobial susceptibility, carbapenemase detection, testing for the presence of efflux pump by broth microdilution and loss of porin by sodium dodecyl sulfate polyacrylamide gel electrophoresis...
February 9, 2017: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/28289035/wck-5107-zidebactam-wck-5153-novel-inhibitors-of-pbp2-showing-potent-%C3%AE-lactam-enhancer-activity-against-pseudomonas-aeruginosa-including-multidrug-resistant-metallo-%C3%AE-lactamase-producing-high-risk-clones
#6
Bartolome Moya, Isabel M Barcelo, Sachin Bhagwat, Mahesh Patel, German Bou, Krisztina M Papp-Wallace, Robert A Bonomo, Antonio Oliver
Zidebactam and WCK 5153 are novel β-lactam enhancers that are bicyclo-acyl hydrazides (BCH), derivatives of diazabicyclooctane (DBO) scaffold, targeted for the treatment of serious infections caused by highly drug-resistant Gram-negative pathogens. In this report, we determined the PBP inhibition profiles and the antimicrobial activity of zidebactam and WCK 5153 against P. aeruginosa, including multidrug-resistant (MDR) metallo-β-lactamase (MBL)-producing high-risk clones. MICs and time-kill assays were conducted for zidebactam, WCK 5153 and antipseudomonal β-lactams using wild-type PAO1 strain, MexAB-OprM-hyperproducing (mexR), porin deficient (oprD) and AmpC-hyperproducing (dacB) derivatives of PAO1 and MBL-expressing clinical strains, ST175 (blaVIM-2) and ST111 (blaVIM-1)...
March 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28276695/proteomic-assessment-of-the-expression-of-genes-related-to-toluene-catabolism-and-porin-synthesis-in-pseudomonas-stutzeri-st-9
#7
Esti Michael, Margarita Gomila, Jorge Lalucat, Yeshayahu Nitzan, Izabella Pechatnikov, Rivka Cahan
The organization and expression of Pseudomonas stutzeri ST-9 genes related to toluene catabolism and porin synthesis was investigated. Toluene-degrading genes were found to be localized in the chromosome close to a phage-type integrase. A regulatory gene and 21 genes related to an aromatics degradation pathway are organized as a putative operon. These proteins are upregulated in the presence of toluene. Fourteen outer membrane proteins were identified as porins in the ST-9 genome. The identified porins showed that the main detected porins are related to the OmpA and OprD superfamilies...
March 9, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28264855/structural-alteration-of-ompr-as-a-source-of-ertapenem-resistance-in-a-ctx-m-15-producing-escherichia-coli-o25b-h4-st131-clinical-isolate
#8
Hervé Dupont, Pascaline Choinier, David Roche, Sandine Adiba, Megan Sookdeb, Catherine Branger, Erick Denamur, Hedi Mammeri
In this study, an ertapenem-non-susceptible Escherichia coli isolate was investigated to determine the genetic basis for its carbapenem resistance phenotype. This clinical strain was recovered from a patient that received, one year ago, ertapenem to treat a cholangitis due to a carbapenem-susceptible extended-spectrum β-lactamase (ESBL)-producing E. coli isolate. Whole-genome sequencing of these strains was performed using Illumina and single molecule real-time sequencing technologies. It revealed that they belonged to the ST131 clonal group, had the predicted O25b:H4 serotype, and produced the CTX-M-15 and TEM-1 β-lactamases...
March 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28242707/oligomeric-lipoprotein-pelc-guides-pel-polysaccharide-export-across-the-outer-membrane-of-pseudomonas-aeruginosa
#9
Lindsey S Marmont, Jacquelyn D Rich, John C Whitney, Gregory B Whitfield, Henrik Almblad, Howard Robinson, Matthew R Parsek, Joe J Harrison, P Lynne Howell
Secreted polysaccharides are important functional and structural components of bacterial biofilms. The opportunistic pathogen Pseudomonas aeruginosa produces the cationic exopolysaccharide Pel, which protects bacteria from aminoglycoside antibiotics and contributes to biofilm architecture through ionic interactions with extracellular DNA. A bioinformatics analysis of genome databases suggests that gene clusters for Pel biosynthesis are present in >125 bacterial species, yet little is known about how this biofilm exopolysaccharide is synthesized and exported from the cell...
February 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28242667/in-vitro-selection-of-meropenem-resistance-among-ceftazidime-avibactam-resistant-meropenem-susceptible-klebsiella-pneumoniae-isolates-with-variant-kpc-3-carbapenemases
#10
Ryan K Shields, M Hong Nguyen, Ellen G Press, Liang Chen, Barry N Kreiswirth, Cornelius J Clancy
Ceftazidime-avibactam resistance is mediated by blaKPC-3 mutations, which restore carbapenem susceptibility. We subjected blaKPC-3 mutant (n=5) and wild-type (n=2) K. pneumoniae isolates to serial meropenem passage. Meropenem MICs against all isolates increased. Ompk36 porin mutations evolved in 5 isolates, including those with wild-type blaKPC-3 In different passage lineages, blaKPC-3 mutations reverted to wild-type, were replaced by new mutations, or were retained. Carbapenem treatment of ceftazidime-avibactam resistant K...
February 27, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28242258/impact-of-defined-cell-envelope-mutations-in-escherichia-coli-on-the-in-vitro-antibacterial-activity-of-avibactam-%C3%AE-lactam-combinations
#11
Sarah M McLeod, Sara A Patey, Michael D Huband, Wright W Nichols
Avibactam is a novel non-β-lactam β-lactamase inhibitor being developed in combination with ceftazidime, ceftaroline and aztreonam for the treatment of infections caused by Gram-negative bacteria. Avibactam protects the antibacterial activity of these antibiotics by inhibiting Ambler classes A and C and some class D β-lactamases. The Gram-negative cell envelope presents a complex barrier to hydrophilic solutes and contains multiple molecular determinants of antibiotic susceptibility and resistance. To investigate the role of some of these determinants in the activity of avibactam and its partner antibiotics in Escherichia coli, an isogenic panel with deletions in specific components of the cell envelope was constructed in an E...
February 24, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28230771/antibiotic-resistance-determinant-focused-acinetobacter-baumannii-vaccine-designed-using-reverse-vaccinology
#12
Zhaohui Ni, Yan Chen, Edison Ong, Yongqun He
As one of the most influential and troublesome human pathogens, Acinetobacter baumannii (A. baumannii) has emerged with many multidrug-resistant strains. After collecting 33 complete A. baumannii genomes and 84 representative antibiotic resistance determinants, we used the Vaxign reverse vaccinology approach to predict classical type vaccine candidates against A. baumannii infections and new type vaccine candidates against antibiotic resistance. Our genome analysis identified 35 outer membrane or extracellular adhesins that are conserved among all 33 genomes, have no human protein homology, and have less than 2 transmembrane helices...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28216041/structure-of-a-type-1-secretion-system-abc-transporter
#13
Jacob L W Morgan, Justin F Acheson, Jochen Zimmer
Type-1 secretion systems (T1SSs) represent a widespread mode of protein secretion across the cell envelope in Gram-negative bacteria. The T1SS is composed of an inner-membrane ABC transporter, a periplasmic membrane-fusion protein, and an outer-membrane porin. These three components assemble into a complex spanning both membranes and providing a conduit for the translocation of unfolded polypeptides. We show that ATP hydrolysis and assembly of the entire T1SS complex is necessary for protein secretion. Furthermore, we present a 3...
March 7, 2017: Structure
https://www.readbyqxmd.com/read/28199365/click-chemistry-approach-to-study-mycoloylated-proteins-evidence-for-porb-and-porc-porins-mycoloylation-in-corynebacterium-glutamicum
#14
Hanane Issa, Emilie Huc-Claustre, Thamila Reddad, Nolwenn Bonadé Bottino, Maryelle Tropis, Christine Houssin, Mamadou Daffé, Nicolas Bayan, Nathalie Dautin
Protein mycoloylation is a recently identified, new form of protein acylation. This post-translational modification consists in the covalent attachment of mycolic acids residues to serine. Mycolic acids are long chain, α-branched, β-hydroxylated fatty acids that are exclusively found in the cell envelope of Corynebacteriales, a bacterial order that includes important genera such as Mycobacterium, Nocardia or Corynebacterium. So far, only 3 mycoloylated proteins have been identified: PorA, PorH and ProtX from C...
2017: PloS One
https://www.readbyqxmd.com/read/28198105/antibiotic-dependent-perturbations-of-extended-spectrum-beta-lactamase-producing-klebsiella-pneumoniae-proteome
#15
Moo-Jin Suh, Sarah L Keasey, Ernst E Brueggemann, Robert G Ulrich
Extended spectrum beta-lactamase producing Klebsiella pneumoniae (ESBL-KP) causes life-threatening infections in susceptible and immuno-compromised individuals. Because of the emergence of multidrug resistance and tolerance, it is crucial to better understand the mechanisms by which ESBL-KP can adapt to antibiotic stress. The aim of this study was to provide an overview of the global proteome changes occurring in ESBL-KP in response to sub-lethal concentrations of the antibiotics doxycycline (DC, bacteriostatic) and streptomycin (SM, bactericidal), which both impair ribosomal synthesis of bacterial proteins...
February 15, 2017: Proteomics
https://www.readbyqxmd.com/read/28177769/a-deletion-variant-partially-complements-a-porin-less-strain-of-i-neurospora-crassa-i
#16
Fraser G Ferens, Victor Spicer, Oleg V Krokhin, Anna Motnenko, William A T Summers, Deborah A Court
Mitochondrial porin, the voltage-dependent anion channel, plays an important role in metabolism and other cellular functions within eukaryotic cells. To further the understanding of porin structure and function, <i>Neurospora crassa</i> wild-type porin was replaced with a deletion variant lacking residues 238-242 (238porin). 238porin was assembled in the mitochondrial outer membrane, but the steady state levels were only about 3% of those of the wild-type protein. The strain harbouring 238porin displayed cytochrome deficiencies and expressed alternative oxidase...
November 2, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28157293/a-whole-cell-based-assay-to-evaluate-structure-permeation-relationships-for-carbapenem-passage-through-the-pseudomonas-aeruginosa-porin-oprd
#17
Ramkumar Iyer, Mark A Sylvester, Camilo Velez-Vega, Ruben Tommasi, Thomas F Durand-Reville, Alita A Miller
The global emergence of antibiotic resistance, especially in Gram-negative bacteria, is an urgent threat to public health. Discovery of novel classes of antibiotics with activity against these pathogens has been impeded by a fundamental lack of understanding of the molecular drivers underlying small molecule uptake. Although it is well-known that outer membrane porins represent the main route of entry for small, hydrophilic molecules across the Gram-negative cell envelope, the structure-permeation relationship for porin passage has yet to be defined...
February 3, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28155846/rationalizing-the-permeation-of-polar-antibiotics-into-gram-negative-bacteria
#18
Mariano Andrea Scorciapino, Silvia Acosta-Gutierrez, Dehbia Benkerrou, Tommaso D'Agostino, Giuliano Malloci, Susruta Samanta, Igor Bodrenko, Matteo Ceccarelli
The increasing level of antibiotic resistance in Gram-negative bacteria, together with the lack of new potential drug scaffolds in the pipeline, make the problem of infectious diseases a global challenge for modern medicine. The main reason that Gram-negative bacteria are particularly challenging is the presence of an outer cell-protecting membrane, which is not present in Gram-positive species. Such an asymmetric bilayer is a highly effective barrier for polar molecules. Several protein systems are expressed in the outer membrane to control the internal concentration of both nutrients and noxious species, in particular: (i) water-filled channels that modulate the permeation of polar molecules and ions according to concentration gradients, and (ii) efflux pumps to actively expel toxic compounds...
March 22, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/28137507/construction-and-evaluation-of-an-edwardsiella-tarda-dna-vaccine-encoding-outer-membrane-protein-c
#19
Fuguo Liu, Xiaoqian Tang, Xiuzhen Sheng, Jing Xing, Wenbin Zhan
Outer membrane protein C is a porin that resides in the outer membrane, and it has been identified as an antigenic protein in many bacteria, such as Escherichia coli, Salmonella typhi, Aeromonas hydrophila and Edwardsiella tarda. In the present work, we aimed at evaluating the immune protective potential of E. tarda OmpC as a DNA vaccine. For this purpose, a recombinant DNA plasmid encoding OmpC (pCG-OmpC) gene was constructed and its vaccine potential was analyzed in a flounder (Paralichthys olivaceus) model...
March 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28133574/panel-strain-of-klebsiella-pneumoniae-for-beta-lactam-antibiotic-evaluation-their-phenotypic-and-genotypic-characterization
#20
Roshan Dsouza, Naina Adren Pinto, InSik Hwang, YoungLag Cho, Dongeun Yong, Jongrak Choi, Kyungwon Lee, Yunsop Chong
Klebsiella pneumoniae is responsible for numerous infections caused in hospitals, leading to mortality and morbidity. It has been evolving as a multi-drug resistant pathogen, acquiring multiple resistances such as such as horizontal gene transfer, transposon-mediated insertions or change in outer membrane permeability. Therefore, constant efforts are being carried out to control the infections using various antibiotic therapies. Considering the severity of the acquired resistance, we developed a panel of strains of K...
2017: PeerJ
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