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Quantitative Proteomic Analysis Reveals Unique Hsp90 Cycle-Dependent Client Interactions, Erick I Rios, Davi Gonçalves, Kevin A Morano, Jill L Johnson

Journal Articles

Hsp90 is an abundant and essential molecular chaperone that mediates the folding and activation of client proteins in a nucleotide-dependent cycle. Hsp90 inhibition directly or indirectly impacts the function of 10-15% of all proteins due to degradation of client proteins or indirect downstream effects. Due to its role in chaperoning oncogenic proteins, Hsp90 is an important drug target. However, compounds that occupy the ATP-binding pocket and broadly inhibit function have not achieved widespread use due to negative effects. More selective inhibitors are needed; however, it is unclear how to achieve selective inhibition. We conducted a quantitative proteomic analysis of soluble …

Evaluation Of Fusobacterium Nucleatum Enoyl-Acp Reductase (Fabk) As A Narrow-Spectrum Drug Target, Jacob T Rutherford, Kristiana Avad, Chetna Dureja, Krissada Norseeda, Bibek Gc, Chenggang Wu, Dianqing Sun, Kirk E Hevener, Julian G Hurdle

Journal Articles

Fusobacterium nucleatum, a pathobiont inhabiting the oral cavity, contributes to opportunistic diseases, such as periodontal diseases and gastrointestinal cancers, which involve microbiota imbalance. Broad-spectrum antimicrobial agents, while effective against F. nucleatum infections, can exacerbate dysbiosis. This necessitates the discovery of more targeted narrow-spectrum antimicrobial agents. We therefore investigated the potential for the fusobacterial enoyl-ACP reductase II (ENR II) isoenzyme FnFabK (C4N14_ 04250) as a narrow-spectrum drug target. ENRs catalyze the rate-limiting step in the bacterial fatty acid synthesis pathway. Bioinformatics revealed that of the four distinct bacterial ENR isoforms, F. nucleatum specifically encodes FnFabK. Genetic studies revealed …

Optimization Of The Antifungal Properties Of The Bacterial Peptide Entv By Variant Analysis, Shantanu Guha, Shane A Cristy, Giuseppe Buda De Cesare, Melissa R Cruz, Michael C Lorenz, Danielle A Garsin

Journal Articles

Fungal resistance to commonly used medicines is a growing public health threat, and there is a dire need to develop new classes of antifungals. We previously described a peptide produced by Enterococcus faecalis, EntV, that restricts Candida albicans to a benign form rather than having direct fungicidal activity. Moreover, we showed that one 12-amino acid (aa) alpha helix of this peptide retained full activity, with partial activity down to the 10aa alpha helix. Using these peptides as a starting point, the current investigation sought to identify the critical features necessary for antifungal activity and to screen for new variants …

Quorum-Sensing, Magdalena Podkowik, Andrew I Perault, Gregory Putzel, Andrew Pountain, Jisun Kim, Ashley L Dumont, Erin E Zwack, Robert J Ulrich, Theodora K Karagounis, Chunyi Zhou, Andreas F Haag, Julia Shenderovich, Gregory A Wasserman, Junbeom Kwon, John Chen, Anthony R Richardson, Jeffrey N Weiser, Carla R Nowosad, Desmond S Lun, Dane Parker, Alejandro Pironti, Xilin Zhao, Karl Drlica, Itai Yanai, Victor J Torres, Bo Shopsin

Journal Articles

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δagr cells undergo a shift towards a hyperactive metabolic …

Synergistic Effects Of Β-Nafeo2 Ferrite Nanoparticles For Photocatalytic Degradation, Antibacterial, And Antioxidant Applications, Tahira Jabeen, Muhammad Shahid Khan, Sana Javaid, Waqar Azeem, Rabia Ayoub, Martin Motola

Journal Articles

Here, synthesis and thorough characterization of β-NaFeO2 nanoparticles utilizing a co-precipitation technique is presented. XRD analysis confirmed a hexagonal-phase structure of β-NaFeO2. SEM revealed well-dispersed spherical nanoparticles with an average diameter of 45 nm. The FTIR spectrum analysis revealed weak adsorption bands at 1054 cm-1 suggested metal-metal bond stretching (Fe-Na). UV-Visible spectroscopy indicates a 4.4 eV optical band gap. Colloidal stability of β-NaFeO2 was evidenced via Zeta potential (-28.5 mV) and Dynamic Light Scattering (DLS) measurements. BET analysis reveals a substantial 343.27 m2 g-1 surface area with mesoporous characteristics. Antioxidant analysis indicates efficacy comparable to standard antioxidants, while concentration-dependent antibacterial …

Genomes Of Bacteroides Ovatus, B. Cellulosilyticus, B. Uniformis, Phocaeicola Vulgatus, And P. Dorei Isolated From Gut Cavernous Fistulous Tract Micropathologies In Crohn's Disease, Vaidhvi Singh, Gail West, Claudio Fiocchi, Fabio Cominelli, Caryn E Good, Michael R Jacobs, Alexander Rodriguez-Palacios

Journal Articles

Surgically removed bowels from Crohn's disease patients exhibit a novel form of micropathologies known as cavernous fistulous tract microlesions (CavFT), resembling fissures. We announce the genomes/plasmids and antimicrobial resistance genes of six CavFT bacterial isolates representing the Bacteroidota genera Bacteroides and Phocaeicola. Plasmids were identified in Bacteroides cellulosilyticus and Phocaeicola vulgatus.

Cytoplasmic Redox Imbalance In The Thioredoxin System Activates Hsf1 And Results In Hyperaccumulation Of The Sequestrase Hsp42 With Misfolded Proteins., Davi Goncalves, Duong Long Duy, Sara Peffer, Kevin A Morano

Journal Articles

Cells employ multiple systems to maintain homeostasis when experiencing environmental stress. For example, the folding of nascent polypeptides is exquisitely sensitive to proteotoxic stressors including heat, pH, and oxidative stress, and is safeguarded by a network of protein chaperones that concentrate potentially toxic misfolded proteins into transient assemblies to promote folding or degradation. The redox environment itself is buffered by both cytosolic and organellar thioredoxin and glutathione pathways. How these systems are linked is poorly understood. Here, we determine that specific disruption of the cytosolic thioredoxin system resulted in constitutive activation of the heat shock response in Saccharomyces cerevisiae and …

Draft Genome Sequences Of Pseudomonas Strains Zfem001-005 Isolated From The Intestine Of Larval Zebrafish Danio Rerio, Sabona B Simbassa, Justin Clark, Keiko Salazar, Anthony Maresso, Anne-Marie Krachler

Journal Articles

Here, we report the draft genome sequences of Pseudomonas strains zfem001–005, five isolates from the intestinal microbiota of healthy larval zebrafish Danio rerio at a developmental age of 7 days post fertilization. The isolates have been identified as Pseudomonas sediminis, Pseudomonas japonica, Pseudomonas otitidis, Pseudomonas sichuanensis, and Pseudomonas tohonis, respectively.

Chimeric Systems Composed Of Swapped Tra Subunits Between Distantly-Related F Plasmids Reveal Striking Plasticity Among Type Iv Secretion Machines, Kouhei Kishida, Yang Grace Li, Natsumi Ogawa-Kishida, Pratick Khara, Abu Amar M Al Mamun, Rachel E Bosserman, Peter J Christie

Journal Articles

Bacterial type IV secretion systems (T4SSs) are a versatile family of macromolecular translocators, collectively able to recruit diverse DNA and protein substrates and deliver them to a wide range of cell types. Presently, there is little understanding of how T4SSs recognize substrate repertoires and form productive contacts with specific target cells. Although T4SSs are composed of a number of conserved subunits and adopt certain conserved structural features, they also display considerable compositional and structural diversity. Here, we explored the structural bases underlying the functional versatility of T4SSs through systematic deletion and subunit swapping between two conjugation systems encoded by the …

Macromolecular Crowding, Phase Separation, And Homeostasis In The Orchestration Of Bacterial Cellular Functions, Begoña Monterroso, William Margolin, Arnold J Boersma, Germán Rivas, Bert Poolman, Silvia Zorrilla

Journal Articles

Macromolecular crowding affects the activity of proteins and functional macromolecular complexes in all cells, including bacteria. Crowding, together with physicochemical parameters such as pH, ionic strength, and the energy status, influences the structure of the cytoplasm and thereby indirectly macromolecular function. Notably, crowding also promotes the formation of biomolecular condensates by phase separation, initially identified in eukaryotic cells but more recently discovered to play key functions in bacteria. Bacterial cells require a variety of mechanisms to maintain physicochemical homeostasis, in particular in environments with fluctuating conditions, and the formation of biomolecular condensates is emerging as one such mechanism. In this …

Exploring The Antibacterial Potential And Underlying Mechanisms Of Prunella Vulgaris L. On Methicillin-Resistant Staphylococcus Aureus, Ziyin Li, Qiqi He, Feifei Xu, Xinxin Yin, Zhuofan Guan, Jia Song, Zhini He, Xingfen Yang, Chen Situ

Journal Articles

Prunella vulgaris L. (PV) is a widely distributed plant species, known for its versatile applications in both traditional and contemporary medicine, as well as in functional food development. Despite its broad-spectrum antimicrobial utility, the specific mechanism of antibacterial action remains elusive. To fill this knowledge gap, the present study investigated the antibacterial properties of PV extracts against methicillin-resistant Staphylococcus aureus (MRSA) and assessed their mechanistic impact on bacterial cells and cellular functions. The aqueous extract of PV demonstrated greater anti-MRSA activity compared to the ethanolic and methanolic extracts. UPLC-ESI-MS/MS tentatively identified 28 phytochemical components in the aqueous extract of PV. …

A Mutation In F-Actin Polymerization Factor Suppresses The Distal Arthrogryposis Type 5 Piezo2 Pathogenic Variant In Caenorhabditis Elegans, Xiaofei Bai, Harold E Smith, Luis O Romero, Briar Bell, Valeria Vásquez, Andy Golden

Journal Articles

The mechanosensitive PIEZO channel family has been linked to over 26 disorders and diseases. Although progress has been made in understanding these channels at the structural and functional levels, the underlying mechanisms of PIEZO-associated diseases remain elusive. In this study, we engineered four PIEZO-based disease models using CRISPR/Cas9 gene editing. We performed an unbiased chemical mutagen-based genetic suppressor screen to identify putative suppressors of a conserved gain-of-function variant pezo-1[R2405P] that in human PIEZO2 causes distal arthrogryposis type 5 (DA5; p. R2718P). Electrophysiological analyses indicate that pezo-1(R2405P) is a gain-of-function allele. Using genomic mapping and whole-genome sequencing approaches, we identified a …

A Kinesin-13 Family Kinesin In Trypanosoma Brucei Regulates Cytokinesis And Cytoskeleton Morphogenesis By Promoting Microtubule Bundling, Huiqing Hu, Yasuhiro Kurasawa, Qing Zhou, Ziyin Li

Journal Articles

The early branching eukaryote Trypanosoma brucei divides uni-directionally along the longitudinal cell axis from the cell anterior toward the cell posterior, and the cleavage furrow ingresses along the cell division plane between the new and the old flagella of a dividing bi-flagellated cell. Regulation of cytokinesis in T. brucei involves actomyosin-independent machineries and trypanosome-specific signaling pathways, but the molecular mechanisms underlying cell division plane positioning remain poorly understood. Here we report a kinesin-13 family protein, KIN13-5, that functions downstream of FPRC in the cytokinesis regulatory pathway and determines cell division plane placement. KIN13-5 localizes to multiple cytoskeletal structures, interacts …

Comprehensive Characterization Of Polyproline Tri-Helix Macrocyclic Nanoscaffolds For Predictive Ligand Positioning., Chia-Lung Tsai, Je-Wei Chang, Kum-Yi Cheng, Yu-Jing Lan, Yi-Cheng Hsu, Qun-Da Lin, Tzu-Yuan Chen, Orion Shih, Chih-Hsun Lin, Po-Hsun Chiang, Mantas Simenas, Vidmantas Kalendra, Yun-Wei Chiang, Chun-Hsien Chen, U-Ser Jeng, Sheng-Kai Wang

Journal Articles

Multivalent ligands hold promise for enhancing avidity and selectivity to simultaneously target multimeric proteins, as well as potentially modulating receptor signaling in pharmaceutical applications. Essential for these manipulations are nanosized scaffolds that precisely control ligand display patterns, which can be achieved by using polyproline oligo-helix macrocyclic nanoscaffolds via selective binding to protein oligomers and cell surface receptors. This work focuses on synthesis and structural characterization of different-sized polyproline tri-helix macrocyclic (PP3M) scaffolds. Through combined analysis of circular dichroism (CD), small- and wide-angle X-ray scattering (SWAXS), electron spin resonance (ESR) spectroscopy, and molecular modeling, a non-coplanar tri-helix loop structure with partially …

Conserved Residues At The Mtr4 C-Terminus Coordinate Helicase Activity And Exosome Interactions, Matthew K Yim, Catherine J Stuart, Markell I Pond, Ambro Van Hoof, Sean J Johnson

Journal Articles

Mtr4 is an essential RNA helicase involved in nuclear RNA processing and degradation and is a member of the Ski2-like helicase family. Ski2-like helicases share a common core architecture that includes two RecA-like domains, a winged helix, and a helical bundle (HB) domain. In Mtr4, a short C-terminal tail immediately follows the HB domain and is positioned at the interface of the RecA-like domains. The tail ends with a SLYΦ sequence motif that is highly conserved in a subset of Ski2-like helicases. Here, we show that this sequence is critical for Mtr4 function. Mutations in the C-terminus result in decreased …

Microbial Co-Occurrences On Catheters From Long-Term Catheterized Patients, Taylor M Nye, Zongsen Zou, Chloe L P Obernuefemann, Jerome S Pinkner, Erin Lowry, Kent Kleinschmidt, Karla Bergeron, Aleksandra Klim, Karen W Dodson, Ana L Flores-Mireles, Jennifer N Walker, Daniel Garrett Wong, Alana Desai, Michael G Caparon, Scott J Hultgren

Journal Articles

Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in catheter and urine samples from 55 human long-term catheterized patients collected over one year. Although most of these patients were prescribed antibiotics over several collection periods, their catheter samples remain colonized by one or more bacterial species. Examination of a total of 366 catheter and urine samples identify 13 positive and 13 negative genus co-occurrences over 12 collection periods, representing associations that occur more or less frequently than expected …

A Bibliometric Analysis Of Literatures On Uterine Leiomyosarcoma In The Last 20 Years, Jinhua Huang, Yu Chen, Ziyin Li, Mimi Chen, Dingwen Huang, Peixin Zhu, Xintong Han, Yi Zheng, Xiaochun Chen, Zhiying Yu

Journal Articles

Background: Uterine leiomyosarcoma(uLMS) is a rare malignant tumor with low clinical specificity and poor prognosis.There are many studies related to uLMS, however, there is still a lack of metrological analyses with generalization. This study provides a bibliometric study of uLMS.

Methods and materials: We chose the Web of Science (WoS) as our main database due to its extensive interdisciplinary coverage. We specifically focused on the literature from the last 20 years to ensure relevance and practicality. By utilizing the WOS core dataset and leveraging the R package "bibliometric version 4.1.0" and Citespace, we performed a comprehensive bibliometric analysis. This allowed …

Colonization Of Larval Zebrafish (Danio Rerio) With Adherent-Invasive Escherichia Coli Prevents Recovery Of The Intestinal Mucosa From Drug-Induced Enterocolitis, Erika Flores, Soumita Dutta, Rachel Bosserman, Ambro Van Hoof, Anne-Marie Krachler

Journal Articles

Although inflammatory bowel diseases are on the rise, what factors influence IBD risk and severity, and the underlying mechanisms remain to be fully understood. Although host genetics, microbiome, and environmental factors have all been shown to correlate with the development of IBD, cause and effect are difficult to disentangle in this context. For example, AIEC is a known pathobiont found in IBD patients, but it remains unclear if gut inflammation during IBD facilitates colonization with AIEC, or if AIEC colonization makes the host more susceptible to pro-inflammatory stimuli. It is critical to understand the mechanisms that contribute to AIEC infections …

Bacterial Outer Membrane Vesicles Provide An Alternative Pathway For Trafficking Of Escherichia Coli O157 Type Iii Secreted Effectors To Epithelial Cells, Natalie Sirisaengtaksin, Eloise J O'Donoghue, Sara Jabbari, Andrew J Roe, Anne Marie Krachler

Journal Articles

Outer membrane vesicles (OMVs) are proteoliposomes shed by Gram-negative bacteria. Their secretion is enhanced by the transition into the intra-host milieu, and OMVs play critical roles during pathogenesis. Enterohemorrhagic Escherichia coli O157 (EHEC) can cause diarrheal disease in humans, and soluble toxins including Shiga-like toxins that contribute to disease severity and clinical complications like hemolytic uremic syndrome have been shown to be OMV associated. In addition to Shiga-like toxins, EHEC produces a type III secretion system (T3SS), and T3SS effectors are associated with colonization and disease severity in vivo. Here, we show that type III secreted substrates including translocators …

Illuminating Type Iv Secretion-Mediated Dna Trafficking Through Long Filaments, Peter J Christie

Journal Articles

No abstract provided.

Benzodioxane-Benzamides As Ftsz Inhibitors: Effects Of Linker's Functionalization On Gram-Positive Antimicrobial Activity, Lorenzo Suigo, William Margolin, Eugenia Ulzurrun, Martina Hrast Rambaher, Carlo Zanotto, Victor Sebastián-Pérez, Nuria E Campillo, Valentina Straniero, Ermanno Valoti

Journal Articles

FtsZ is an essential bacterial protein abundantly studied as a novel and promising target for antimicrobials. FtsZ is highly conserved among bacteria and mycobacteria, and it is crucial for the correct outcome of the cell division process, as it is responsible for the division of the parent bacterial cell into two daughter cells. In recent years, the benzodioxane-benzamide class has emerged as very promising and capable of targeting both Gram-positive and Gram-negative FtsZs. In this study, we explored the effect of including a substituent on the ethylenic linker between the two main moieties on the antimicrobial activity and pharmacokinetic properties. …

Cbx4 Promotes Antitumor Immunity By Suppressing Pdcd1 Expression In T Cells., Liwei Ren, Ziyin Li, Yu Zhou, Jun Zhang, Ziheng Zhao, Zhaofei Wu, Ye Zhao, Yurong Ju, Xuewen Pang, Xiuyuan Sun, Wei Wang, Yu Zhang

Journal Articles

E3 SUMO-protein ligase CBX4 (CBX4), a key component of polycomb-repressive complexes 1 (PRC1), has been reported to regulate a variety of genes implicated in tumor growth, metastasis, and angiogenesis. However, its role in T-cell-mediated antitumor immunity remains elusive. To shed light on this issue, we generated mice with T-cell-specific deletion of Cbx4. Tumor growth was increased in the knockout mice. Additionally, their tumor-infiltrating lymphocytes exhibited impaired tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) production, with an elevated programmed cell death protein 1 (PD-1) level. In fact, dysregulated Pdcd1 expression was observed in all major subsets of peripheral T cells from …

Rcc2 Promotes Prostate Cancer Cell Proliferation And Migration Through Hh/Gli1 Signaling Pathway And Cancer Stem-Like Cells, Shenghan Wang, Zhentao Lei, Wei Liu, Jie Xiong, Yuqiang Shi, Lin Yang, Qiang Gao, Kai Le, Bao Zhang

Journal Articles

BACKGROUND: Regulator of chromosome condensation 2 (RCC2) was a telophase disk-binding protein on mitosis, and functions as an oncogene in many human cancers. However, its role on prostate cancer (PCa) was unknown. The goal of this study is to explore the function of RCC 2 on PCa development.

METHODS: The expression of RCC2 and its methylation level, its correlation with lymph node metastasis or disease-free survival (DFS) was analyzed using TCGA database. The effect of RCC2 on PCa cell proliferation, migration and invasion were detected using CCK-8, cell colony formation, Transwell and wood healing assays. RNA-seq and GSEA analysis were …

A Conceptual Framework For Nomenclatural Stability And Validity Of Medically Important Fungi: A Proposed Global Consensus Guideline For Fungal Name Changes Supported By Abp, Asm, Clsi, Ecmm, Escmid-Efisg, Eucast-Afst, Fdlc, Idsa, Isham, Mmsa, And Msgerc., Sybren De Hoog, Thomas J Walsh, Sarah A Ahmed, Ana Alastruey-Izquierdo, Barbara D Alexander, Maiken Cavling Arendrup, Esther Babady, Feng-Yan Bai, Joan-Miquel Balada-Llasat, Andrew Borman, Anuradha Chowdhary, Andrew Clark, Robert C Colgrove, Oliver A Cornely, Tanis C Dingle, Philippe J Dufresne, Jeff Fuller, Jean-Pierre Gangneux, Connie Gibas, Heather Glasgow, Yvonne Gräser, Jacques Guillot, Andreas H Groll, Gerhard Haase, Kimberly Hanson, Amanda Harrington, David L Hawksworth, Randall T Hayden, Martin Hoenigl, Vit Hubka, Kristie Johnson, Julianne V Kus, Ruoyu Li, Jacques F Meis, Michaela Lackner, Fanny Lanternier, Sixto M Leal, Francesca Lee, Shawn R Lockhart, Paul Luethy, Isabella Martin, Kyung J Kwon-Chung, Wieland Meyer, M Hong Nguyen, Luis Ostrosky-Zeichner, Elizabeth Palavecino, Preeti Pancholi, Peter G Pappas, Gary W Procop, Scott A Redhead, Daniel D Rhoads, Stefan Riedel, Bryan Stevens, Kaede Ota Sullivan, Paschalis Vergidis, Emmanuel Roilides, Amir Seyedmousavi, Lili Tao, Vania A Vicente, Roxana G Vitale, Qi-Ming Wang, Nancy L Wengenack, Lars Westblade, Nathan Wiederhold, Lewis White, Christina M Wojewoda, Sean X Zhang

Journal Articles

The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the …

Candida Auris-Macrophage Cellular Interactions And Transcriptional Response, Pedro Miramón, Andrew W Pountain, Michael C Lorenz

Journal Articles

The pathogenic yeast Candida auris represents a global threat of the utmost clinical relevance. This emerging fungal species is remarkable in its resistance to commonly used antifungal agents and its persistence in the nosocomial settings. The innate immune system is one the first lines of defense preventing the dissemination of pathogens in the host. C. auris is susceptible to circulating phagocytes, and understanding the molecular details of these interactions may suggest routes to improved therapies. In this work, we examined the interactions of this yeast with macrophages. We found that macrophages avidly phagocytose C. auris; however, intracellular replication is …

The Microtubule Quartet Protein Snap1 In Trypanosoma Brucei Facilitates Flagellum And Cell Division Plane Positioning By Promoting Basal Body Segregation, Thiago Souza Onofre, Kieu T M Pham, Qing Zhou, Ziyin Li

Journal Articles

The unicellular protozoan Trypanosoma brucei has a single flagellum that is involved in cell motility, cell morphogenesis, and cell division. Inheritance of the newly assembled flagellum during the cell cycle requires its correct positioning, which depends on the faithful duplication or segregation of multiple flagellum-associated cytoskeletal structures, including the basal body, the flagellum attachment zone, and the hook complex. Along the flagellum attachment zone sites a set of four microtubules termed the microtubule quartet (MtQ), whose molecular function remains enigmatic. We recently reported that the MtQ-localized protein NHL1 interacts with the microtubule-binding protein TbSpef1 and regulates flagellum inheritance by promoting …

Ligand-Displaying Escherichia Coli Cells And Minicells For Programmable Delivery Of Toxic Payloads Via Type Iv Secretion Systems, Yang Grace Li, Kouhei Kishida, Natsumi Ogawa-Kishida, Peter J Christie

Journal Articles

Bacterial type IV secretion systems (T4SSs) are highly versatile macromolecular translocators and offer great potential for deployment as delivery systems for therapeutic intervention. One major T4SS subfamily, the conjugation machines, are well-adapted for delivery of DNA cargoes of interest to other bacteria or eukaryotic cells but generally exhibit modest transfer frequencies and lack specificity for target cells. Here, we tested the efficacy of a surface-displayed nanobody/antigen (Nb/Ag) pairing system to enhance the conjugative transfer of IncN (pKM101), IncF (F/pOX38), or IncP (RP4) plasmids, or of mobilizable plasmids including those encoding CRISPR/Cas9 systems (pCrispr), to targeted recipient cells. Escherichia coli donors …

Coordination Between Aminoacylation And Editing To Protect Against Proteotoxicity, Hong Zhang, Parker Murphy, Jason Yu, Sukyeong Lee, Francis T F Tsai, Ambro Van Hoof, Jiqiang Ling

Journal Articles

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that ligate amino acids to tRNAs, and often require editing to ensure accurate protein synthesis. Recessive mutations in aaRSs cause various neurological disorders in humans, yet the underlying mechanism remains poorly understood. Pathogenic aaRS mutations frequently cause protein destabilization and aminoacylation deficiency. In this study, we report that combined aminoacylation and editing defects cause severe proteotoxicity. We show that the ths1-C268A mutation in yeast threonyl-tRNA synthetase (ThrRS) abolishes editing and causes heat sensitivity. Surprisingly, experimental evolution of the mutant results in intragenic mutations that restore heat resistance but not editing. ths1-C268A destabilizes ThrRS and …

Catalase Produced By Candida Albicans Protects Streptococcus Mutans From H2o2 Stress-One More Piece In The Cross-Kingdom Synergism Puzzle, Callahan Katrak, Bruna A Garcia, Louise M Dornelas-Figueira, Mary Nguyen, Robert B Williams, Michael C Lorenz, Jacqueline Abranches

Journal Articles

Co-infection with Streptococcus mutans and Candida albicans is associated with dental caries, and their co-cultivation results in enhanced biofilm matrix production that contributes to increased virulence and caries risk. Moreover, the catalase-negative S. mutans demonstrates increased oxidative stress tolerance when co-cultivated in biofilms with C. albicans, a catalase-producing yeast. Here, we sought to obtain mechanistic insights into the increased H2O2 tolerance of S. mutans when co-cultivated with clinical isolates of Candida glabrata, Candida tropicalis, and C. albicans. Additionally, the C. albicans SC5314 laboratory strain, its catalase mutant (SC5314Δcat1), and S. mutans UA159 and its glucosyltransferase B/C …

State-Of-The-Art In Carbides/Carbon Composites For Electromagnetic Wave Absorption, Bo Hu, Lixue Gai, Yonglei Liu, Pan Wang, Shuping Yu, Li Zhu, Xijiang Han, Yunchen Du

Journal Articles

Electromagnetic wave absorbing materials (EWAMs) have made great progress in the past decades, and are playing an increasingly important role in radiation prevention and antiradar detection due to their essential attenuation toward incident EM wave. With the flourish of nanotechnology, the design of high-performance EWAMs is not just dependent on the intrinsic characteristics of single-component medium, but pays more attention to the synergistic effects from different components to generate rich loss mechanisms. Among various candidates, carbides and carbon materials are usually labeled with the features of chemical stability, low density, tunable dielectric property, and diversified morphology/microstructure, and thus the combination …