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Type III Secretion System

Julia P Steringer, Walter Nickel
As illustrated by a diverse set of examples in this special issue, multiple mechanisms of protein secretion have been identified in eukaryotes that do not involve the endoplasmic reticulum (ER) and the Golgi apparatus. Here we focus on the type I pathway with Fibroblast Growth Factor 2 (FGF2) being the most prominent example. Unconventional secretion of FGF2 from cells is mediated by direct protein translocation across the plasma membrane. A unique feature of this process is the ability of FGF2 to form its own membrane translocation intermediate through oligomerization and membrane insertion...
February 16, 2018: Seminars in Cell & Developmental Biology
Akira Kitamura, Yoshihito Ishida, Hiroshi Kubota, Chan-Gi Pack, Takayuki Homma, Shinya Ito, Kazutaka Araki, Masataka Kinjo, Kazuhiro Nagata
Heat shock protein 47 kDa (HSP47), an ER-resident and collagen-specific molecular chaperone, recognizes collagenous hydrophobic amino acid sequences (Gly-Pro-Hyp) and assists in secretion of correctly folded collagen. Elevated collagen production is correlated with HSP47 expression in various diseases, including fibrosis and keloid. HSP47 knockdown ameliorates liver fibrosis by inhibiting collagen secretion, and inhibition of the interaction of HSP47 with procollagen also prevents collagen secretion. Therefore, a high-throughput system for screening of drugs capable of inhibiting the interaction between HSP47 and collagen would aid the development of novel therapies for fibrotic diseases...
February 10, 2018: Biochemical and Biophysical Research Communications
Amy Smith, Amelia H Lovelace, Brian H Kvitko
Pseudomonas syringae pv. tomato DC3000 is an important model plant pathogen, with a fully annotated genome and multiple compatible plant hosts. Very few studies have examined the regulation of DC3000 gene expression in vivo. We developed a quantitative reverse transcription-polymerase chain reaction assay to monitor transcriptional changes in DC3000 inoculated into Arabidopsis thaliana leaves during disease and exposure to pattern-triggered immunity (PTI). In our approach, bacterial RNA concentrations in total tissue RNA are standardized using P...
February 13, 2018: Molecular Plant-microbe Interactions: MPMI
Dai Wang, Sean P McAteer, Agata B Wawszczyk, Clark D Russell, Amin Tahoun, Alex Elmi, Scott L Cockroft, David Tollervey, Sander Granneman, Jai J Tree, David L Gally
The prokaryotic RNA chaperone Hfq mediates sRNA-mRNA interactions and plays a significant role in post-transcriptional regulation of the type III secretion (T3S) system produced by a range of Escherichia coli pathotypes. UV-crosslinking was used to map Hfq-binding under conditions that promote T3S and multiple interactions were identified within polycistronic transcripts produced from the locus of enterocyte effacement (LEE) that encodes the T3S system. The majority of Hfq binding was within the LEE5 and LEE4 operons, the latter encoding the translocon apparatus (SepL-EspADB) that is positively regulated by the RNA binding protein, CsrA...
February 8, 2018: Nucleic Acids Research
Huanying Pang, Mingsheng Qiu, Jingmin Zhao, Rowena Hoare, Sean J Monaghan, Dawei Song, Yunsheng Chang, Jichang Jian
Vibrio alginolyticus, a bacterial pathogen in fish and humans, expresses a type III secretion system (T3SS) that is critical for pathogen virulence and disease development. However, little is known about the associated effectors (T3SEs) and their physiological role. In this study, the T3SE gene hopPmaJ (hop) was cloned from V. alginolyticus wild-type strain HY9901 and the mutant strain HY9901Δhop was constructed by the in-frame deletion method. The results showed that the deduced amino acid sequence of V. alginolyticus HopPmaJ shared 78-98% homology with other Vibrio spp...
February 7, 2018: Fish & Shellfish Immunology
A Edrees, H Abdelhamed, S W Nho, S B Park, A Karsi, F W Austin, M Essa, T Pechan, M L Lawrence
Catfish is the largest aquaculture industry in the United States. Edwardsiellosis is considered one of the most significant problems affecting this industry. Edwardsiella piscicida is a newly described species within the genus Edwardsiella, and it was previously classified as Edwardsiella tarda. It causes gastrointestinal septicaemia, primarily in summer months, in farmed channel catfish in the south-eastern United States. In the current study, we adapted gene deletion methods used for Edwardsiella to E. piscicida strain C07-087, which was isolated from a disease outbreak in a catfish production pond...
February 9, 2018: Journal of Fish Diseases
Rahul Kumar, Sunil Kumar Yadav, Durga M Swain, Gopaljee Jha
Fungal pathogens are responsible for approximately two third of the infectious plant diseases. Historically they have been associated with several devastating famines, causing death and disabilities in humans. Mostly fungal diseases are being controlled by using fungicides which otherwise have adverse side effects on the health of consumers as well as environment. Due to extensive usages, pathogens have evolved resistance against most of the commonly used fungicides and rendered them ineffective. Controlling fungal disease in a sustainable and eco-friendly fashion remains a challenge...
December 31, 2017: Microbial Cell
Daniela Santos Pontes, Rodrigo Santos Aquino de Araujo, Natalina Dantas, Luciana Scotti, Marcus Tullius Scotti, Ricardo Olimpio de Moura, Francisco Jaime Bezerra Mendonca-Junior
The ever increasing number of multidrug-resistant microorganism pathogens has become a great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms of resistance are intimately associated, but comprehension of the biochemical and molecular functions of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the emergence and impacts of antibiotic resistance...
February 5, 2018: Current Topics in Medicinal Chemistry
Fang Bai, Zhenpeng Li, Akihiro Umezawa, Naohiro Terada, Shouguang Jin
A protein delivery tool based on bacterial type III secretion system (T3SS) has been broadly applied in biomedical researches. In this review, we summarize various applications of the T3SS-mediate protein delivery which enables translocation of proteins directly into mammalian cells without protein purification. Some of the remarkable advancements include delivery of antigens for therapeutic vaccines, nucleases for genome editing, transcription factors for cellular reprogramming and stem cells differentiation, and signaling molecules for post-translational proteomics studies...
February 2, 2018: Biotechnology Advances
Hagit Salem, Yekaterina Yatchenko, Mariana Anosov, Talya Rosenfeld, Gheona Altarescu, Sorina Grisaru-Granovsky, Ruth Birk
Irisin is a novel secreted myokine, encoded by the fibronectin type III domain-containing protein 5 (FNDC5) precursor gene. Irisin plays a role in the female reproductive system in pregnancy and in embryonic development, and is associated with fetal size. It is expressed in the ovary, placenta and neonatal cord serum. We studied whether maternal and neonatal FNDC5 genetic polymorphisms are associated with preterm birth (PTB). Blood for DNA analysis was collected from Israeli mothers (n = 315) and from umbilical veins of their respected idiopathic preterm (24-36 weeks) and control term (>37 weeks) newborns (n = 161)...
January 30, 2018: Gene
Laurent Dortet, Charlotte Lombardi, François Cretin, Andréa Dessen, Alain Filloux
Recent studies highlight that bacterial pathogens can reprogram target cells by influencing epigenetic factors. The type III secretion system (T3SS) is a bacterial nanomachine that resembles a syringe on the bacterial surface. The T3SS 'needle' delivers translocon proteins into eukaryotic cell membranes, subsequently allowing injection of bacterial effectors into the cytosol. Here we show that Pseudomonas aeruginosa induces early T3SS-dependent dephosphorylation and deacetylation of histone H3 in eukaryotic cells...
February 5, 2018: Nature Microbiology
Sarah E Kralicek, Mai Nguyen, Ki-Jong Rhee, Rocio Tapia, Gail Hecht
Enteropathogenic Escherichia coli (EPEC) is a foodborne pathogen that uses a type III secretion system to translocate effector molecules into host intestinal epithelial cells (IECs) subverting several host cell processes and signaling cascades. Interestingly, EPEC infection induces only modest intestinal inflammation in the host. The homologous EPEC effector proteins, NleH1 and NleH2, suppress the nuclear factor-κB (NF-κB) pathway and apoptosis in vitro. Increased apoptosis and activation of NF-κB and MAP kinases (MAPK) contribute to the pathogenesis of inflammatory bowel diseases (IBD)...
February 2, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Andrés Zalguizuri, Gustavo Caetano-Anollés, Viviana Claudia Lepek
In the establishment and maintenance of the interaction between pathogenic or symbiotic bacteria with a eukaryotic organism, protein substrates of specialized bacterial secretion systems called effectors play a critical role once translocated into the host cell. Proteins are also secreted to the extracellular medium by free-living bacteria or directly injected into other competing organisms to hinder or kill. In this work, we explore an approach based on the evolutionary dependence that most of the effectors maintain with their specific secretion system that analyzes the co-occurrence of any orthologous protein group and their corresponding secretion system across multiple genomes...
January 31, 2018: Briefings in Bioinformatics
Antje Munder, Justin Rothschuh, Bastian Schirmer, Jens Klockgether, Volkhard Kaever, Burkhard Tümmler, Roland Seifert, Christina Kloth
The nucleotidyl cyclase ExoY is an effector protein of the type III secretion system of Pseudomonas aeruginosa We compared the cyclic nucleotide production and lung disease phenotypes caused by the ExoY-overexpressing strain PA103ΔexoUexoT::Tc pUCPexoY, its vector control strain PA103ΔexoUexoT::Tc pUCP18, its loss-of-function control PA103ΔexoUexoT::Tc pUCPexoY K81M and natural ExoY-positive and ExoY-negative isolates in a murine acute airway infection model. Only the P. aeruginosa carrier of the exoY-plasmid produced high levels of cUMP and caused the most severe course of infection...
January 2018: Open Biology
Doron Teper, Anil Madhusoodana Girija, Eran Bosis, Georgy Popov, Alon Savidor, Guido Sessa
The Gram-negative bacterium Xanthomonas euvesicatoria (Xe) is the causal agent of bacterial spot disease of pepper and tomato. Xe delivers effector proteins into host cells through the type III secretion system to promote disease. Here, we show that the Xe effector XopAU, which is conserved in numerous Xanthomonas species, is a catalytically active protein kinase and contributes to the development of disease symptoms in pepper plants. Agrobacterium-mediated expression of XopAU in host and non-host plants activated typical defense responses, including MAP kinase phosphorylation, accumulation of pathogenesis-related (PR) proteins and elicitation of cell death, that were dependent on the kinase activity of the effector...
January 29, 2018: PLoS Pathogens
Srinivasan V Narayanan, Miguel A Perez-Pinzon
Ischemic preconditioning (IPC) represents a potential therapy against cerebral ischemia. While our group has previously shown IPC to induce neuroprotection through various pathways, the role of astrocytes in supporting IPC-induced neuroprotection has not been extensively studied. Astrocyte-derived lactate has gained attention as a potential soluble mediator through which astrocytes could impart ischemic tolerance to neurons. Therefore, the goal of this study was to determine if i) IPC-treatment of astrocytes alone could transfer ischemic tolerance to neurons; ii) if IPC-treatment of astrocytes increases lactate production; and if iii) exogenous lactate administration to neurons could induce neuroprotection against lethal ischemia in vitro...
December 2017: Cond Med
Yong Zhang, Jiaman Li, Weiqi Zhang, Hualei Shi, Feng Luo, Yasufumi Hikichi, Xiaojun Shi, Kouhei Ohnishi
LysR-type transcriptional regulators (LTTRs) are ubiquitous and abundant among bacteria and control a variety of cellular processes. Here, we investigated the effect of Rsc1880 (a putative LTTR, hereafter designated PrhO) on pathogenicity of Ralstonia solanacearum. Deletion of prhO substantially reduced the expression of type III secretion system (T3SS) both in vitro and in planta, and resulted in significantly impaired virulence in tomato and tobacco plants. Complementary prhO completely restored the reduced virulence and T3SS expression to that of wild type...
January 24, 2018: Molecular Plant Pathology
Xiaofeng Zhou, Doron Teper, Maxuel O Andrade, Tong Zhang, Sixue Chen, Wen-Yuan Song, Nian Wang
Most pathogenic bacteria deliver virulence factors into host cytosol through type III secretion systems (T3SS) to perturb host immune responses. The expression of T3SS is often repressed in rich medium but is specifically induced in the host environment. The molecular mechanisms underlying host-specific induction of T3SS expression is not completely understood. Here we demonstrate in Xanthomonas citri that host-induced phosphorylation of the ATP-dependent protease Lon stabilizes HrpG, the master regulator of T3SS, conferring bacterial virulence...
January 23, 2018: MBio
Yumi Ikawa, Sayaka Onishi, Akiko Shoji, Ayako Furutani, Seiji Tsuge
The hrp genes of Xanthomonas oryzae pv. oryzae, the causal agent of bacterial leaf blight of rice, encode components of the type III secretion system and are essential for virulence. Expression of hrp genes is regulated by two key hrp regulators HrpG and HrpX; HrpG regulates hrpX and hrpA, and HrpX regulates the other hrp genes on hrpB-hrpF operons. We previously reported the sugar-dependent quantitative regulation of HrpX; the regulator highly accumulates in the presence of xylose, followed by high hrp gene expression...
January 23, 2018: Molecular Plant-microbe Interactions: MPMI
Yunpeng Guan, Kaiyu Yin, Mian Zhou, Minjun Yang, Yuanxing Zhang, Xiaohong Liu, Qiyao Wang
Edwardsiella piscicida is a gram-negative bacterial pathogen invading a wide range of fish species. Response regulator EsrB is essential for activation of type III and type VI secretion systems (T3/T6SS). In this study, proteomes of the wild type E. piscicida EIB202 and a ΔesrB mutant strains were compared to identify the regulon components of EsrB cultured in DMEM allowing T3/T6SS expression. As a result, 19 proteins showed different expression, which were identified to be associated with T3/T6SS, related to amino acid transport and metabolism, and energy production...
January 15, 2018: FEMS Microbiology Letters
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