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https://www.readbyqxmd.com/read/28642045/mutations-on-ftsz-lateral-helix-h3-that-disrupt-cell-viability-hamper-reorganization-of-polymers-on-lipid-surfaces
#1
Ileana F Márquez, Pablo Mateos-Gil, Jae Yen Shin, Rosalba Lagosb, Octavio Monasterio, Marisela Vélez
FtsZ filaments localize at the middle of the bacterial cell and participate in the formation of a contractile ring responsible for cell division. Previous studies demonstrated that the highly conserved negative charge of glutamate 83 and the positive charge of arginine 85 located in the lateral helix H3 bend of Escherichia coli FtsZ are required for in vivo cell division. In order to understand how these lateral mutations impair the formation of a contractile ring, we extend previous in vitro characterization of these mutants in solution to study their behavior on lipid modified surfaces...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28634179/lessons-from-bacterial-homolog-of-tubulin-ftsz-for-microtubule-dynamics
#2
Rachana Rao Battaje, Dulal Panda
FtsZ, a homolog of tubulin, is found in almost all bacteria and archaea where it has a primary role in cytokinesis. Evidence for structural homology between FtsZ and tubulin came from their crystal structures and identification of the GTP-box. Tubulin and FtsZ constitute a distinct family of GTPases and show striking similarities in many of their polymerization properties. The differences between them, more so, the complexities of microtubule dynamic behavior in comparison to that of FtsZ, indicate that the evolution to tubulin is attributable to the incorporation of the complex functionalities in higher organisms...
June 20, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28633894/synthesis-and-antibacterial-activity-of-5-methylphenanthridium-derivatives-as-ftsz-inhibitors
#3
Fang Liu, Henrietta Venter, Fangchao Bi, Susan J Semple, Jingru Liu, Chaobin Jin, Shutao Ma
5-Methylphenanthridium derivatives were designed, synthesized and evaluated for their in vitro antibacterial activity and cell division inhibitory activity against various Gram-positive and -negative bacteria. Among them, compounds 5A2, 5B1, 5B2, 5B3, 5C1 and 5C2 displayed the best on-target antibacterial activity with an MIC value of 4µg/mL against B. subtilis ATCC9372 and S. pyogenes PS, showing over 2-fold better activity than sanguinarine. The SARs showed that the 5-methylphenanthridium derivatives with the alkyl side chains at the 2-postion, especially the straight alkyl side chains exerted better on-target antibacterial activity...
June 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28630190/%C3%AE-lactam-antibiotics-with-a-high-affinity-for-pbp2-act-synergistically-with-the-ftsz-targeting-agent-txa707-against-methicillin-resistant-staphylococcus-aureus
#4
Edgar Ferrer-González, Malvika Kaul, Ajit K Parhi, Edmond J LaVoie, Daniel S Pilch
Methicillin-resistant Staphylococcus aureus (MRSA) is a multi-drug resistant pathogen that poses a significant risk to global health today. We have developed a promising new FtsZ-targeting agent (TXA707) with potent activity against MRSA isolates resistant to current standard-of-care antibiotics. Here we present results that demonstrate differing extents of synergy between TXA707 and a broad range of β-lactam antibiotics (including six cephalosporins, two penicillins, and two carbapenems) against MRSA. To explore whether there is a correlation between the extent of synergy and the preferential antibacterial target of each β-lactam, we determined the binding affinities of the β-lactam antibiotics for each of the four native penicillin binding proteins (PBPs) of S...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630123/absence-of-the-polar-organizing-protein-popz-causes-aberrant-cell-division-in-agrobacterium-tumefaciens
#5
Matthew Howell, Alena Aliashkevich, Anne K Salisbury, Felipe Cava, Grant R Bowman, Pamela J B Brown
Agrobacterium tumefaciens is a rod-shaped bacterium that grows by polar insertion of new peptidoglycan during cell elongation. As the cell cycle progresses, peptidoglycan synthesis at the pole ceases prior to insertion of new peptidoglycan at mid-cell to enable cell division. The A. tumefaciens homolog of the Caulobacter crescentus polar organelle development protein PopZ has been identified as a growth pole marker and a candidate polar growth promoting factor. Here, we characterize the function of PopZ in cell growth and division of A...
June 19, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28625721/kiloniella-majae-sp-nov-isolated-from-spider-crab-maja-brachydactyla-and-pullet-carpet-shell-clam-venerupis-pullastra
#6
Diego Gerpe, Noemí Buján, Ana L Diéguez, Aide Lasa, Jesús L Romalde
Ten Gram-negative, rod-shaped and motile bacterial strains were isolated from spider crab (M27.10, M27.11a, F36.1, F36.4, M56.1, F76.17b, M146.1, M166.3 and M166.6) and pullet carpet shell clam (SBRF 1.10) collected in the coast of Galicia. Analyses of the 16S rRNA genes showed that the strains belong to the genus Kiloniella and have high similarity with the species Kiloniella spongiae (99.44-99.86%) and Kiloniella litopenaei (99.0-99.5%). Strains M56.1(T) (=CECT 9195, =LMG 29925), M146.1 (=CECT 9193, =LMG 29926) and SBRF 1...
June 10, 2017: Systematic and Applied Microbiology
https://www.readbyqxmd.com/read/28623318/zipa-and-ftsa-stabilize-ftsz-gdp-miniring-structures
#7
Yaodong Chen, Haiyan Huang, Masaki Osawa, Harold P Erickson
The cytokinetic division ring of Escherichia coli comprises filaments of FtsZ tethered to the membrane by FtsA and ZipA. Previous results suggested that ZipA is a Z-ring stabilizer, since in vitro experiments it is shown that ZipA enhanced FtsZ assembly and caused the filaments to bundles. However, this function of ZipA has been challenged by recent studies. First, ZipA-induced FtsZ bundling was not significant at pH greater than 7. Second, some FtsA mutants, such as FtsA* were able to bypass the need of ZipA...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621933/structural-flexibility-of-an-inhibitor-overcomes-drug-resistance-mutations-in-staphylococcus-aureus-ftsz
#8
Junso Fujita, Yoko Maeda, Eiichi Mizohata, Tsuyoshi Inoue, Malvika Kaul, Ajit K Parhi, Edmond J LaVoie, Daniel S Pilch, Hiroyoshi Matsumura
In the effort to combat antibiotic resistance, inhibitors of the essential bacterial protein FtsZ have emerged as a promising new class of compounds with clinical potential. One such FtsZ inhibitor (TXA707) is associated with potent activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) that are resistant to current standard-of-care antibiotics. However, mutations in S. aureus FtsZ (SaFtsZ) that confer resistance to TXA707 have been observed, with mutations in the Gly196 and Gly193 residues being among the most prevalent...
June 16, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28616148/the-structural-assembly-switch-of-cell-division-protein-ftsz-probed-with-fluorescent-allosteric-inhibitors
#9
Marta Artola, Laura B Ruíz-Avila, Erney Ramírez-Aportela, R Fernando Martínez, Lidia Araujo-Bazán, Henar Vázquez-Villa, Mar Martín-Fontecha, María A Oliva, A Javier Martín-Galiano, Pablo Chacón, María L López-Rodríguez, José M Andreu, Sonia Huecas
FtsZ is a widely conserved tubulin-like GTPase that directs bacterial cell division and a new target for antibiotic discovery. This protein assembly machine cooperatively polymerizes forming single-stranded filaments, by means of self-switching between inactive and actively associating monomer conformations. The structural switch mechanism was proposed to involve a movement of the C-terminal and N-terminal FtsZ domains, opening a cleft between them, allosterically coupled to the formation of a tight association interface between consecutive subunits along the filament...
February 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28615720/arc6-mediated-z-ring-like-structure-formation-of-prokaryote-descended-chloroplast-ftsz-in-escherichia-coli
#10
Hiroki Irieda, Daisuke Shiomi
Plant chloroplasts proliferate through binary fission, and the stromal-side molecules that are involved in chloroplast division are bacterial derivatives. As in bacteria, the prokaryotic tubulin homolog FtsZ assembles into a ring-like structure (Z ring) at mid-chloroplast, and this process is followed by constriction. However, the properties of chloroplast FtsZs remain unclarified. Here, we employed Escherichia coli as a novel heterologous system for expressing chloroplast FtsZs and their regulatory components...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28613431/a-conserved-coiled-coil-protein-pair-focuses-the-cytokinetic-z-ring-in-caulobacter-crescentus
#11
Selamawit Woldemeskel, Ryan McQuillen, Alex M Hessel, Jie Xiao, Erin D Goley
The cytoskeletal GTPase FtsZ assembles at midcell, recruits the division machinery, and directs envelope invagination for bacterial cytokinesis. ZapA, a conserved FtsZ-binding protein, promotes Z-ring stability and efficient division through a mechanism that is not fully understood. Here we investigated the function of ZapA in Caulobacter crescentus. We found that ZapA is encoded in an operon with a small coiled-coil protein we named ZauP. ZapA and ZauP co-localized at the division site and were each required for efficient division...
June 14, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28611731/the-genomic-architecture-of-novel-simulium-damnosum-wolbachia-prophage-sequence-elements-and-implications-for-onchocerciasis-epidemiology
#12
James L Crainey, Jacob Hurst, Poppy H L Lamberton, Robert A Cheke, Claire E Griffin, Michael D Wilson, Cláudia P Mendes de Araújo, María-Gloria Basáñez, Rory J Post
Research interest in Wolbachia is growing as new discoveries and technical advancements reveal the public health importance of both naturally occurring and artificial infections. Improved understanding of the Wolbachia bacteriophages (WOs) WOcauB2 and WOcauB3 [belonging to a sub-group of four WOs encoding serine recombinases group 1 (sr1WOs)], has enhanced the prospect of novel tools for the genetic manipulation of Wolbachia. The basic biology of sr1WOs, including host range and mode of genomic integration is, however, still poorly understood...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28600514/bactericidal-metabolites-from-phellinus-noxius-hn-1-against-microcystis-aeruginosa
#13
Pengfei Jin, Haonan Wang, Wenbo Liu, Shujian Zhang, Chunhua Lin, Fucong Zheng, Weiguo Miao
Harmful algal blooms cause serious problems worldwide due to large quantities of cyanotoxins produced by cyanobacteria in eutrophic water. In this study, a new compound named 2-(3, 4-dihydroxy-2-methoxyphenyl)-1, 3-benzodioxole-5-carbaldehyde (Compound 1), together with one known compound, 3, 4-dihydroxybenzalacetone (DBL), was purified from Phellinus noxius HN-1 (CCTCC M 2016242). Compound 1 and DBL displayed activity against the cyanobacteria Microcystis aeruginosa with a half maximal effective concentration of 21 and 5 μg/mL, respectively...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28586174/2-6-difluorobenzamide-inhibitors-of-the-bacterial-cell-division-protein-ftsz-design-synthesis-and-structure-activity-relationship-study
#14
Valentina Straniero, Ermanno Valoti, Carlo Zanotto, Letizia Straniero, Andrea Casiraghi, Stefano Duga, Antonia Radaelli, Carlo de Giuli Morghen
A wide variety of drug-resistant microorganism are continuously emerging, restricting the therapy of common bacterial infections. Originally potent antimicrobial agents are now no longer helpful, due to their weak or null activity towards these antibiotic-resistant bacteria. In addition, none of the recently approved antibiotics affects innovative targets, resulting in a requirement of novel drugs, with innovative antibacterial mechanisms of action. The essential cell division protein FtsZ (Filamentous temperature sensitive Z) emerged as a possible target, thanks to its ubiquitous expression and its homology to eukaryotic -tubulin...
June 6, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28555087/strategic-incorporation-of-fluorine-in-the-drug-discovery-of-new-generation-antitubercular-agents-targeting-bacterial-cell-division-protein-ftsz
#15
Iwao Ojima, Divya Awasthi, Longfei Wei, Krupanandan Haranahalli
This article presents an account of our research on the discovery and development of new-generation fluorine-containing antibacterial agents against drug-resistant tuberculosis, targeting FtsZ. FtsZ is an essential protein for bacterial cell division and a highly promising therapeutic target for antibacterial drug discovery. Through design, synthesis and semi-HTP screening of libraries of novel benzimidazoles, followed by SAR studies, we identified highly potent lead compounds. However, these lead compounds were found to lack sufficient metabolic and plasma stabilities...
April 2017: Journal of Fluorine Chemistry
https://www.readbyqxmd.com/read/28554018/in%C3%A2-vitro-evaluation-of-the-cytotoxic-and-bactericidal-mechanism-of-the-commonly-used-pesticide-triphenyltin-hydroxide
#16
Susobhan Mahanty, Darpan Raghav, Krishnan Rathinasamy
Triphenyltin hydroxide (TPTH) is a widely used pesticide that is highly toxic to a variety of organisms including humans and a potential contender for the environmental pollutant. In the present study, the cytotoxic mechanism of TPTH on mammalian cells was analyzed using HeLa cells and the antibacterial activity was analyzed using B. subtilis and E. coli cells. TPTH inhibited the growth of HeLa cells with a half-maximal inhibitory concentration of 0.25 μM and induced mitotic arrest. Immunofluorescence microscopy analysis showed that TPTH caused strong depolymerization of interphase microtubules and spindle abnormality with the appearance of colchicine type mitosis and condensed chromosome...
May 20, 2017: Chemosphere
https://www.readbyqxmd.com/read/28553278/a-thiazole-orange-derivative-targeting-the-bacterial-protein-ftsz-shows-potent-antibacterial-activity
#17
Ning Sun, Yu-Jing Lu, Fung-Yi Chan, Ruo-Lan Du, Yuan-Yuan Zheng, Kun Zhang, Lok-Yan So, Ruben Abagyan, Chao Zhuo, Yun-Chung Leung, Kwok-Yin Wong
The prevalence of multidrug resistance among clinically significant bacteria calls for the urgent development of new antibiotics with novel mechanisms of action. In this study, a new small molecule exhibiting excellent inhibition of bacterial cell division with potent antibacterial activity was discovered through cell-based screening. The compound exhibits a broad spectrum of bactericidal activity, including the methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and NDM-1 Escherichia coli...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28539635/regulation-of-chloroplast-and-nucleomorph-replication-by-the-cell-cycle-in-the-cryptophyte-guillardia-theta
#18
Ryo Onuma, Neha Mishra, Shin-Ya Miyagishima
The chloroplasts of cryptophytes arose through a secondary endosymbiotic event in which a red algal endosymbiont was integrated into a previously nonphotosynthetic eukaryote. The cryptophytes retain a remnant of the endosymbiont nucleus (nucleomorph) that is replicated once in the cell cycle along with the chloroplast. To understand how the chloroplast, nucleomorph and host cell divide in a coordinated manner, we examined the expression of genes/proteins that are related to nucleomorph replication and chloroplast division as well as the timing of nuclear and nucleomorph DNA synthesis in the cryptophyte Guillardia theta...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28525300/regulation-of-cell-polarity-in-motility-and-cell-division-in-myxococcus-xanthus
#19
Dominik Schumacher, Lotte Søgaard-Andersen
Rod-shaped Myxococcus xanthus cells are polarized with proteins asymmetrically localizing to specific positions. This spatial organization is important for regulation of motility and cell division and changes over time. Dedicated protein modules regulate motility independent of the cell cycle, and cell division dependent on the cell cycle. For motility, a leading-lagging cell polarity is established that is inverted during cellular reversals. Establishment and inversion of this polarity are regulated hierarchically by interfacing protein modules that sort polarized motility proteins to the correct cell poles or cause their relocation between cell poles during reversals akin to a spatial toggle switch...
May 19, 2017: Annual Review of Microbiology
https://www.readbyqxmd.com/read/28523271/the-protein-chaperone-clpx-targets-native-and-non-native-aggregated-substrates-for-remodeling-disassembly-and-degradation-with-clpp
#20
Christopher J LaBreck, Shannon May, Marissa G Viola, Joseph Conti, Jodi L Camberg
ClpX is a member of the Clp/Hsp100 family of ATP-dependent chaperones and partners with ClpP, a compartmentalized protease, to degrade protein substrates bearing specific recognition signals. ClpX targets specific proteins for degradation directly or with substrate-specific adaptor proteins. Native substrates of ClpXP include proteins that form large oligomeric assemblies, such as MuA, FtsZ, and Dps in Escherichia coli. To remodel large oligomeric substrates, ClpX utilizes multivalent targeting strategies and discriminates between assembled and unassembled substrate conformations...
2017: Frontiers in Molecular Biosciences
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