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Yi An, Jiawei Wang, Chen Li, André Leier, Tatiana Marquez-Lago, Jonathan Wilksch, Yang Zhang, Geoffrey I Webb, Jiangning Song, Trevor Lithgow
Bacterial effector proteins secreted by various protein secretion systems play crucial roles in host-pathogen interactions. In this context, computational tools capable of accurately predicting effector proteins of the various types of bacterial secretion systems are highly desirable. Existing computational approaches use different machine learning (ML) techniques and heterogeneous features derived from protein sequences and/or structural information. These predictors differ not only in terms of the used ML methods but also with respect to the used curated data sets, the features selection and their prediction performance...
October 24, 2016: Briefings in Bioinformatics
Jamie L Burgess, R Alan Burgess, Yalemi Morales, Jenna M Bouvang, Sean J Johnson, Nicholas E Dickenson
Like many Gram-negative pathogens, Shigella rely on a complex type three secretion system (T3SS) to inject effector proteins into host cells, take over host functions, and ultimately establish infection. Despite these critical roles, the energetics and regulatory mechanisms controlling the T3SS and pathogen virulence remain largely unclear. In this study, we present a series of high-resolution crystal structures of Spa47 and use the structures to model an activated Spa47 oligomer, finding that ATP hydrolysis may be supported by specific sidechain contributions from adjacent protomers within the complex...
October 21, 2016: Journal of Biological Chemistry
Alejandro Romero, Paolo R Saraceni, Susana Merino, Antonio Figueras, Juan M Tomás, Beatriz Novoa
The selection of an experimental animal model is of great importance in the study of bacterial virulence factors. Here, a bath infection of zebrafish larvae is proposed as an alternative model to study the virulence factors of Aeromonas hydrophila. Intraperitoneal infections in mice and trout were compared with bath infections in zebrafish larvae using specific mutants. The great advantage of this model is that bath immersion mimics the natural route of infection, and injury to the tail also provides a natural portal of entry for the bacteria...
2016: Frontiers in Microbiology
Dominic J Pollard, Joanna C Young, Valentina Covarelli, Silvia Herrera-León, Thomas R Connor, Maria Fookes, Danielle Walker, Aurora Echeita, Nicholas R Thomson, Cedric N Berger, Gad Frankel
Salmonella spp. utilize type III secretion systems (T3SS) to translocate effectors into the cytosol of mammalian host cells, subverting cell signaling and facilitating the onset of gastroenteritis. In this study we compared a draft genome assembly of S. enterica subsp. salamae strain 3588/07 (S. salamae) against the genomes of S. enterica subsp. enterica serovar Typhimurium strain LT2 and S. bongori strain 12419. S. salamae encode the Salmonella pathogenicity island (SPI)-1; SPI-2 and the locus of enterocyte effacement (LEE) T3SSs...
October 10, 2016: Infection and Immunity
Shantanu Bhatt, Marisa Egan, Valerie Jenkins, Sarah Muche, Jihad El-Fenej
Enterohemorrhagic and enteropathogenic Escherichia coli are gastrointestinal pathogens that disrupt the intestinal microvilli to form attaching and effacing (A/E) lesions on infected cells and cause diarrhea. This pathomorphological trait is encoded within the pathogenicity island locus of enterocyte effacement (LEE). The LEE houses a type 3 secretion system (T3SS), which upon assembly bridges the bacterial cytosol to that of the host and enables the bacterium to traffic dozens of effectors into the host where they hijack regulatory and signal transduction pathways and contribute to bacterial colonization and disease...
2016: Frontiers in Cellular and Infection Microbiology
Erin R Green, Stacie Clark, Gregory T Crimmins, Matthias Mack, Carol A Kumamoto, Joan Mecsas
All three pathogenic Yersinia species share a conserved virulence plasmid that encodes a Type 3 Secretion System (T3SS) and its associated effector proteins. During mammalian infection, these effectors are injected into innate immune cells, where they block many bactericidal functions, including the production of reactive oxygen species (ROS). However, Y. pseudotuberculosis (Yptb) lacking the T3SS retains the ability to colonize host organs, demonstrating that chromosome-encoded factors are sufficient for growth within mammalian tissue sites...
September 2016: PLoS Pathogens
Hao Tan, Lu Zhang, Qiang Zhao, Ronghao Chen, Chang Liu, Yuding Weng, Qianqian Peng, Fang Bai, Zhihui Cheng, Shouguang Jin, Weihui Wu, Yongxin Jin
DExD/H box RNA helicases play essential roles in various biological processes in prokaryotes and eukaryotes. By screening Pseudomonas aeruginosa strains with mutations in various DExD/H box helicase genes, we identified that deaD was required for bacterial cytotoxicity and virulence in a mouse acute pneumonia model. Compared to a wild-type strain and its complementation strain, the deaD mutant induced less production of proinflammatory cytokines, neutrophil infiltration and lung damage during infection. We further found that the RNA helicase activity of DeaD was required for the expression of type III secretion system (T3SS) genes...
October 2016: FEMS Microbiology Letters
Yvonne T Wu, Connie Tam, Lucia S Zhu, David J Evans, Suzanne M J Fleiszig
PURPOSE: The type III secretion system (T3SS) is a significant virulence determinant for Pseudomonas aeruginosa. Using a rodent model, we found that contact lens (CL)-related corneal infections were associated with lens surface biofilms. Here, we studied the impact of human tear fluid on CL-associated biofilm growth and T3SS expression. METHODS: P. aeruginosa biofilms were formed on contact lenses for up to 7 days with or without human tear fluid, then exposed to tear fluid for 5 or 24 h...
September 23, 2016: Ocular Surface
Michal Ucko, Angelo Colorni, Lidiya Dubytska, Ronald L Thune
An Edwardsiella sp. was isolated from the kidney of diseased groupers (Epinephelus aeneus and E. marginatus) cultured in Eilat (Israel, Red Sea). Affected fish presented a severe suppurative nephritis with large abscesses occasionally spreading into the surrounding musculature. Biochemical profiles and phenotypic comparisons failed to provide a clear identification to the species level, and genetic analysis of the 16S subunit failed to discriminate between Edwardsiella piscicida, E. tarda and E. ictaluri. Analysis of the gyrB gene, however, placed the grouper isolates into the E...
September 26, 2016: Diseases of Aquatic Organisms
Xingming Liu, Lilan Lu, Xinrui Liu, Xiankai Liu, Chao Pan, Erling Feng, Dongshu Wang, Chang Niu, Li Zhu, Hengliang Wang
There are a series of novel effector molecules secreted by the Type Three Secretion System (T3SS) of Shigella spp. reported in recent years. In this study, a proteomic approach is applied to study T3SS effectors systematically. First, proteins secreted by the S. flexneri wild-type strain after Congo Red (CR) induction are separated and identified using two-dimensional electrophoresis (2-DE) to display the relative abundance of all kinds of early effectors for the first time. Then, a gene deletion mutant of known virulence repressor (OspD1) and a gene overexpressed mutant of two known virulence activators (MxiE and IpgC) were constructed and analyzed to discover potential late effectors...
September 23, 2016: Journal of Microbiology and Biotechnology
Xiaohui Xu, Hua Yu, Di Zhang, Junzhi Xiong, Jing Qiu, Rong Xin, Xiaomei He, Halei Sheng, Wenqiang Cai, Lu Jiang, Kebin Zhang, Xiaomei Hu
During infection, bacteria might generate adaptive responses to facilitate their survival and colonization in the host environment. The alarmone guanosine 5'-triphosphate-3'-diphosphate (ppGpp), the levels of which are regulated by the RelA and SpoT enzymes, plays a critical role in mediating bacterial adaptive responses and virulence. However, the mechanism by which ppGpp regulates virulence-associated traits in Pseudomonas aeruginosa is poorly understood. To investigate the regulatory role of ppGpp, the ppGpp-deficient strain ΔRS (relA and spoT gene double mutant) and the complemented strain ΔRS(++) (complemented with relA and spoT genes) were constructed...
November 2016: Microbiological Research
Cecilia M Duarte, Laura A Basile, Andrés Zalguizuri, Viviana C Lepek
Mesorhizobium loti MAFF303099 has a functional Type III secretion system (T3SS) that is involved in the determination of competitiveness for legume nodulation. Here we demonstrate that the transcriptional factor TtsI, which positively regulates T3SS genes expression, is involved in a negative regulation of M. loti swimming motility in soft-agar. Conditions that induce T3SS expression affect flagella production. The same conditions also affect promoter activity of M. loti visN gene, a homolog to the positive regulator of flagellar genes that has been described in other rhizobia...
September 22, 2016: FEMS Microbiology Letters
Christopher A Lopez, Brittany M Miller, Fabian Rivera-Chávez, Eric M Velazquez, Mariana X Byndloss, Alfredo Chávez-Arroyo, Kristen L Lokken, Renée M Tsolis, Sebastian E Winter, Andreas J Bäumler
Citrobacter rodentium uses a type III secretion system (T3SS) to induce colonic crypt hyperplasia in mice, thereby gaining an edge during its competition with the gut microbiota through an unknown mechanism. Here, we show that by triggering colonic crypt hyperplasia, the C. rodentium T3SS induced an excessive expansion of undifferentiated Ki67-positive epithelial cells, which increased oxygenation of the mucosal surface and drove an aerobic C. rodentium expansion in the colon. Treatment of mice with the γ-secretase inhibitor dibenzazepine to diminish Notch-driven colonic crypt hyperplasia curtailed the fitness advantage conferred by aerobic respiration during C...
September 16, 2016: Science
Victoria Auerbuch
Inflammasome-associated innate immune receptors sense host-cell targeting by the type III secretion system (T3SS) of pathogenic Yersinia. In this issue of Cell Host & Microbe, Chung et al. (2016) show that the Yersinia T3SS effector protein YopM counteracts this recognition pathway by restricting the pyrin inflammasome, thus increasing bacterial fitness.
September 14, 2016: Cell Host & Microbe
Shaohui Wang, Xin Liu, Xuan Xu, Denghui Yang, Dong Wang, Xiangan Han, Yonghong Shi, Mingxing Tian, Chan Ding, Daxin Peng, Shengqing Yu
Type III secretion systems (T3SSs) are crucial for bacterial infections because they deliver effector proteins into host cells. The Escherichia coli type III secretion system 2 (ETT2) is present in the majority of E. coli strains, and although it is degenerate, ETT2 regulates bacterial virulence. An ATPase is essential for T3SS secretion, but the function of the ETT2 ATPase has not been demonstrated. Here, we show that EivC is homologous to the β subunit of F0F1 ATPases and it possesses ATPase activity. To investigate the effects of ETT2 ATPase EivC on the phenotype and virulence of avian pathogenic Escherichia coli (APEC), eivC mutant and complemented strains were constructed and characterized...
2016: Frontiers in Microbiology
M A Pallett, V F Crepin, N Serafini, M Habibzay, O Kotik, J Sanchez-Garrido, J P Di Santo, A R Shenoy, C N Berger, G Frankel
The human pathogen enteropathogenic Escherichia coli (EPEC), as well as the mouse pathogen Citrobacter rodentium, colonize the gut mucosa via attaching and effacing lesion formation and cause diarrheal diseases. EPEC and C. rodentium type III secretion system (T3SS) effectors repress innate immune responses and infiltration of immune cells. Inflammatory caspases such as caspase-1 and caspase-4/11 are crucial mediators of host defense and inflammation in the gut via their ability to process cytokines such as interleukin (IL)-1β and IL-18...
September 14, 2016: Mucosal Immunology
Hilo Yen, Masaki Karino, Toru Tobe
Innate immunity is an essential component in the protection of a host against pathogens. Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively) are known to modulate the innate immune responses of infected cells. The interference is dependent on their type III secretion system (T3SS) and T3SS-dependent effector proteins. Furthermore, these cytosolically injected effectors have been demonstrated to engage multiple immune signaling pathways, including the IFN/STAT, MAPK, NF-κB, and inflammasome pathways...
2016: Frontiers in Cellular and Infection Microbiology
Sebastián Riquelme, Macarena Varas, Camila Valenzuela, Paula Velozo, Nicolás Chahin, Paulina Aguilera, Andrea Sabag, Bayron Labra, Sergio A Álvarez, Francisco P Chávez, Carlos A Santiviago
The social amoeba Dictyostelium discoideum has proven to be a useful model for studying relevant aspects of the host-pathogen interaction. In this work, D. discoideum was used as a model to study the ability of Salmonella Typhimurium to survive in amoebae and to evaluate the contribution of selected genes in this process. To do this, we performed infection assays using axenic cultures of D. discoideum co-cultured with wild-type S. Typhimurium and/or defined mutant strains. Our results confirmed that wild-type S...
2016: Frontiers in Microbiology
Carol Smith, Anne M Stringer, Chunhong Mao, Michael J Palumbo, Joseph T Wade
UNLABELLED: Salmonella enterica pathogenicity island 1 (SPI-1) encodes proteins required for invasion of gut epithelial cells. The timing of invasion is tightly controlled by a complex regulatory network. The transcription factor (TF) HilD is the master regulator of this process and senses environmental signals associated with invasion. HilD activates transcription of genes within and outside SPI-1, including six other TFs. Thus, the transcriptional program associated with host cell invasion is controlled by at least 7 TFs...
2016: MBio
Brian C Russo, Luisa M Stamm, Matthijs Raaben, Caleb M Kim, Emily Kahoud, Lindsey R Robinson, Sayantan Bose, Ana L Queiroz, Bobby Brooke Herrera, Leigh A Baxt, Nirit Mor-Vaknin, Yang Fu, Gabriel Molina, David M Markovitz, Sean P Whelan, Marcia B Goldberg
Type 3 secretion systems (T3SSs) of bacterial pathogens translocate bacterial effector proteins that mediate disease into the eukaryotic cytosol. Effectors traverse the plasma membrane through a translocon pore formed by T3SS proteins. In a genome-wide selection, we identified the intermediate filament vimentin as required for infection by the T3SS-dependent pathogen S. flexneri. We found that vimentin is required for efficient T3SS translocation of effectors by S. flexneri and other pathogens that use T3SS, Salmonella enterica serovar Typhimurium and Yersinia pseudotuberculosis...
2016: Nature Microbiology
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