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Erin P McCauley, Hanh Lam, Nicholas Lorig-Roach, Justin Luu, Cameron Lloyd, Karen Tenney, Halina Pietraszkiewicz, Cristina Diaz, Frederick A Valeriote, Victoria Auerbuch, Phillip Crews
This research set out to identify compounds from marine sponges that can act as bacterial virulence blockers. Extracts from a total of 80 sponges collected from throughout Indonesia were screened in a high-throughput NF-κB-based screen that identifies compounds capable of inhibiting the bacterial type III secretion system (T3SS) in Yersinia pseudotuberculosis. An extract that was shown to inhibit T3SS-driven NF-κB expression was obtained from an Iotrochota cf. iota sponge and was the source of seven new bromo- and iodo-containing compounds, all of which contain a 2-(4-oxyphenyl)ethan-1-amine core...
November 16, 2017: Journal of Natural Products
Abram R Bernard, T Carson Jessop, Prashant Kumar, Nicholas E Dickenson
Type three secretion systems (T3SS) are specialized nano-machines that support infection by injecting bacterial proteins directly into host cells. The Shigella T3SS has uniquely evolved to sense environmental levels of the bile salt deoxycholate (DOC) and up-regulate virulence in response to DOC. In this study, we describe a rare i+5 hydrogen bonding secondary structure element (π-helix) within the type three secretion system tip protein IpaD that plays a critical role in DOC-enhanced virulence. Specifically, engineered mutations within the π-helix altered the pathogen's response to DOC with one mutant construct in particular exhibiting an unprecedented reduction in virulence following DOC exposure...
November 14, 2017: Biochemistry
Jinxin Liu, Zhe Zhao, Yiqing Deng, Yan Shi, Yupeng Liu, Chao Wu, Peng Luo, Chaoqun Hu
Vibrio spp. are the most common pathogens for animals reared in aquaculture. Vibrio campbellii, which is often involved in shrimp, fish and mollusks diseases, is widely distributed in the marine environment worldwide, but our knowledge about its pathogenesis and antimicrobial resistance is very limited. The existence of this knowledge gap is at least partially because that V. campbellii was originally classified as Vibrio harveyi, and the detailed information of its comparative genome analysis to other Vibrio spp...
2017: Frontiers in Microbiology
Massiel Cepeda-Molero, Cedric N Berger, Alistair D S Walsham, Samuel J Ellis, Simon Wemyss-Holden, Stephanie Schüller, Gad Frankel, Luis Ángel Fernández
Enteropathogenic E. coli (EPEC) is a human pathogen that causes acute and chronic pediatric diarrhea. The hallmark of EPEC infection is the formation of attaching and effacing (A/E) lesions in the intestinal epithelium. Formation of A/E lesions is mediated by genes located on the pathogenicity island locus of enterocyte effacement (LEE), which encode the adhesin intimin, a type III secretion system (T3SS) and six effectors, including the essential translocated intimin receptor (Tir). Seventeen additional effectors are encoded by genes located outside the LEE, in insertion elements and prophages...
October 2017: PLoS Pathogens
Weiqi Zhang, Jing Li, Yu Tang, Kai Chen, Xiaojun Shi, Kouhei Ohnishi, Yong Zhang
Previously, we isolated several genes that potentially affected the expression of type III secretion system (T3SS) in Ralstonia solanacearum OE1-1. Here, we focused on the rsp0316, which encodes a putative 2-nitropropane dioxygenase (hereafter designated NpdA). The deletion of npdA substantially reduced the T3SS expression and virulence in OE1-1, and the complementation with functional NpdA could completely restore its reduced T3SS expression and virulence to that of wild type. The NpdA was highly conserved among diverse R...
2017: Frontiers in Microbiology
A V Grishin, S I Luyksaar, L N Kapotina, D D Kirsanov, E S Zayakin, A S Karyagina, N A Zigangirova
Chlamydia trachomatis is a widespread sexually transmitted pathogen that resides within a special vacuole inside host cells. Although acute infection can be treated with antibiotics, chlamydia can enter persistent state, leading to chronic infection that is difficult to cure. Thus, novel anti-chlamydial compounds active against persistent chlamydia are required. Chlamydia rely upon type III secretion system (T3SS) to inject effector proteins into host cell cytoplasm, and T3SS inhibitor are viewed as promising compounds for treatment of chlamydial infections...
October 25, 2017: Chemical Biology & Drug Design
Mickael Vourc'h, Antoine Roquilly, Alexis Broquet, Gaelle David, Philippe Hulin, Cedric Jacqueline, Jocelyne Caillon, Christelle Retiere, Karim Asehnoune
Pseudomonas aeruginosa (PA) expresses the type III secretion system (T3SS) and effector exoenzymes that interfere with intracellular pathways. Natural killer (NK) cells play a key role in antibacterial immunity and their activation is highly dependent on IL-12 produced by myeloid cells. We studied PA and NK cell interactions and the role of IL-12 using human peripheral blood mononuclear cells, sorted human NK cells, and a human NK cell line (NK92). We used a wild-type (WT) strain of PA (PAO1) or isogenic PA-deleted strains to delineate the role of T3SS and exoenzymes...
2017: Frontiers in Immunology
Huifang Cao, Cuiting Yang, Shu Quan, Tianjian Hu, Lingzhi Zhang, Yuanxing Zhang, Dahai Yang, Qin Liu
Bacterium usually utilizes type III secretion systems (T3SS) to deliver effectors directly into host cells with the aids of chaperones. Hence, it is very important to identify bacterial T3SS effectors and chaperones for better understanding of host-pathogen interactions. Edwardsiella piscicida is an invasive enteric bacterium, which infects a wide range of hosts from fish to human. Given E. piscicida encodes a functional T3SS to promote infection, very few T3SS effectors and chaperones have been identified in this bacterium so far...
October 11, 2017: Cellular Microbiology
Kyung Moon, Richard P Bonocora, David D Kim, Qing Chen, Joseph T Wade, Scott Stibitz, Deborah M Hinton
Nearly all virulence factors in Bordetella pertussis are activated by a master two-component system, BvgAS, composed of the sensor kinase BvgS and the response regulator BvgA. When BvgS is active, BvgA is phosphorylated (BvgA~P), and virulence-activated genes (vags) are expressed [Bvg(+) mode]. When BvgS is inactive and BvgA is not phosphorylated, virulence-repressed genes (vrgs) are induced [Bvg(-) mode]. Here, we have used transcriptome sequencing (RNA-seq) and reverse transcription-quantitative PCR (RT-qPCR) to define the BvgAS-dependent regulon of B...
October 10, 2017: MBio
Grandjean Teddy, Boucher Anne, Thepaut Marion, Monlezun Laura, Guery Benoit, Faudry Eric, Kipnis Eric, Dessein Rodrigue
While NLRC4-dependent sensing of intracellular Gram-negative pathogens such as Salmonella Typhimurium is a beneficial host response, NLRC4-dependent sensing of the Pseudomonas aeruginosa type 3 secretion system (T3SS) has been shown to be involved in pathogenicity. In mice, different pathogen-associated microbial patterns are sensed by the combination of the NLRC4-inflammasome with different members of neuronal apoptosis inhibitory protein (NAIPs). NAIP2 is involved in sensing PscI, an inner-rod protein of the P...
August 28, 2017: International Immunology
Irit Tseytin, Avner Dagan, Sonia Oren, Neta Sal-Man
The type III secretion system (T3SS) is a multi-protein complex that plays a central role in the virulence of many Gram-negative bacterial pathogens. In enteropathogenic Escherichia coli, a prevalent cause of diarrheal diseases, the needle complex base of the T3SS is formed by multi-rings: two concentric inner-membrane rings made by the two oligomerizing proteins (EscD and EscJ), and an outer ring made of a single oligomerizing protein (EscC). Although the oligomerization activity of these proteins is critical for their function and can, therefore, affect the virulence of the pathogen, the mechanisms underlying the oligomerization of these proteins have yet to be identified...
October 4, 2017: Biochimica et Biophysica Acta
Pongpan Songwattana, Rujirek Noisangiam, Kamonluck Teamtisong, Janpen Prakamhang, Albin Teulet, Panlada Tittabutr, Pongdet Piromyou, Nantakorn Boonkerd, Eric Giraud, Neung Teaumroong
The Bradyrhizobium sp. DOA9 strain isolated from a paddy field has the ability to nodulate a wide spectrum of legumes. Unlike other bradyrhizobia, this strain has a symbiotic plasmid harboring nod, nif, and type 3 secretion system (T3SS) genes. This T3SS cluster contains all the genes necessary for the formation of the secretory apparatus and the transcriptional activator (TtsI), which is preceded by a nod-box motif. An in silico search predicted 14 effectors putatively translocated by this T3SS machinery. In this study, we explored the role of the T3SS in the symbiotic performance of DOA9 by evaluating the ability of a T3SS mutant (ΩrhcN) to nodulate legumes belonging to Dalbergioid, Millettioid, and Genistoid tribes...
2017: Frontiers in Microbiology
Yi-Fan Zhang, Kook Han, Courtney E Chandler, Brian Tjaden, Robert K Ernst, Stephen Lory
During environmental adaptation bacteria use small regulatory RNAs (sRNAs) to repress or activate expression of a large fraction of their proteome. We extended the use of the in vivo RNA proximity ligation method towards probing global sRNA interactions with their targets in Pseudomonas aeruginosa and verified the method with a known regulon controlled by the PrrF1 sRNA. We also identified two sRNAs (Sr0161 and ErsA) that interact with the mRNA encoding the major porin OprD responsible for the uptake of carbapenem antibiotics...
October 4, 2017: Molecular Microbiology
Jae Hoon Lee, Youfu Zhao
The bacterial enhancer binding protein (bEBP) HrpS is essential for Erwinia amylovora virulence by activating the type III secretion system (T3SS). However, how the hrpS gene is regulated remains poorly understood in E. amylovora. In this study, 5' rapid amplification of cDNA ends and promoter deletion analyses showed that the hrpS gene contains two promoters driven by HrpX/HrpY and the Rcs phosphorelay system, respectively. Electrophoretic mobility shift and gene expression assays demonstrated that integration host factor IHF positively regulates hrpS expression through directly binding the hrpX promoter and positively regulating hrpX/hrpY expression...
September 30, 2017: Molecular Genetics and Genomics: MGG
Yong Zhang, Jing Li, Weiqi Zhang, Rongsheng Wang, Qiaoqing Qiu, Feng Luo, Yasufumi Hikichi, Kouhei Ohnishi, Wei Ding
Hydroxycinnamic acids (HCAs) are typical monocyclic phenylpropanoids, including cinnamic acid (Cin), coumaric acid (Cou), caffeic acid (Caf), ferulic acid (FA) and their isomers, and involved in the interactions between pathogens and host plants. Here, we focused on the impact of HCAs on expression of type III secretion system (T3SS) in Ralstonia solanacearum. FA significantly induced the expression of the T3SS and some type III effectors (T3Es) genes in hrp-inducing medium, while did not the other HCAs. However, exogenously supplemented FA did not affect the T3SS expression in planta and the elicitation of the hypersensitive response (HR) in tobacco leaves...
2017: Frontiers in Plant Science
Laura Chalupowicz, Gal Nissan, Maria T Brandl, Michael McClelland, Guido Sessa, Georgy Popov, Isaac Barash, Shulamit Manulis-Sasson
Salmonella enterica serovar Typhimurium, a human enteric pathogen, has the ability to multiply and survive endophytically in plants. Genes encoding the type III secretion system (T3SS) or its effectors (T3Es) may contribute to its colonization. Two reporter plasmids for T3E translocation into plant cells that are based on hypersensitive response (HR) domains of avirulence proteins from the Pantoea agglomerans/beet and Xanthomonas euvesicatoria/pepper pathosystems were employed in this study to investigate the role of T3Es in the interaction of S...
September 27, 2017: Molecular Plant-microbe Interactions: MPMI
Giulia Pilla, Gareth McVicker, Christoph M Tang
Acquisition of a single copy, large virulence plasmid, pINV, led to the emergence of Shigella spp. from Escherichia coli. The plasmid encodes a Type III secretion system (T3SS) on a 30 kb pathogenicity island (PAI), and is maintained in a bacterial population through a series of toxin:antitoxin (TA) systems which mediate post-segregational killing (PSK). The T3SS imposes a significant cost on the bacterium, and strains which have lost the plasmid and/or genes encoding the T3SS grow faster than wild-type strains in the laboratory, and fail to bind the indicator dye Congo Red (CR)...
September 2017: PLoS Genetics
Shaohui Wang, Xuan Xu, Xin Liu, Dong Wang, Hua Liang, Xiaojun Wu, Mingxing Tian, Chan Ding, Guijun Wang, Shengqing Yu
The Escherichia coli type III secretion system 2 (ETT2) is found in most E. coli strains, including pathogenic and commensal strains. Although many ETT2 gene clusters carry multiple genetic mutations or deletions, ETT2 is known to be involved in bacterial virulence. In enterohaemorrhagic E. coli (EHEC), ETT2 affects adhesion through the regulator EtrA, which regulates transcription and secretion of the type III secretion system (T3SS) encoded by the locus of enterocyte effacement (LEE). To date, no studies have been conducted on the role of EtrA in the virulence of avian pathogenic E...
September 12, 2017: Microbiology
Aditi, Malini Shariff, Sunil K Chhabra, Mujeeb-Ur Rahman
PURPOSE: Pseudomonas aeruginosa is one of the agents that are commonly implicated in nosocomial infections. However, it is also present as a commensal in various body sites of healthy persons, making the diagnosis of infection by culture difficult. A number of virulence factors expressed by the organism have been implicated in its pathogenicity. We undertook this study to identify the host and organism factors associated with infection. METHODOLOGY: Pathogenic, colonizing and environmental isolates were tested for apr, lasB, the T3SS effector exoenzymes (exoS, exoT, exoU and exoY) and toxA genes, biofilm production and antimicrobial susceptibility...
October 2017: Journal of Medical Microbiology
Ronan R McCarthy, Martina Valentini, Alain Filloux
Bacteria produce toxins to enhance their competitiveness in the colonization of an environment as well as during an infection. The delivery of toxins into target cells is mediated by several types of secretion systems, among them our focus is Type III and Type VI Secretion Systems (T3SS and T6SS, respectively). A thorough methodology is provided detailing how to identify if cyclic di-GMP signaling plays a role in the P. aeruginosa toxin delivery mediated by T3SS or T6SS. This includes in vitro preparation of the samples for Western blot analysis aiming at detecting possible c-di-GMP-dependent T3SS/T6SS switch, as well as in vivo analysis using the model organism Galleria mellonella to demonstrate the ecological and pathogenic consequence of the switch between these two secretion systems...
2017: Methods in Molecular Biology
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