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Jonida Toska, Brian T Ho, John J Mekalanos
The type 6 secretion system (T6SS) is a nanomachine used by many Gram-negative bacteria, including Vibrio cholerae , to deliver toxic effector proteins into adjacent eukaryotic and bacterial cells. Because the activity of the T6SS is dependent on direct contact between cells, its activity is limited to bacteria growing on solid surfaces or in biofilms. V. cholerae can produce an exopolysaccharide (EPS) matrix that plays a role in adhesion and biofilm formation. In this work, we investigated the effect of EPS production on T6SS activity between cells...
July 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Christina G Aas, Finn Drabløs, Kjersti Haugum, Jan E Afset
Shiga toxin-producing Escherichia coli (STEC) cause both sporadic infections and outbreaks of enteric disease in humans, with symptoms ranging from asymptomatic carriage to severe disease like haemolytic uremic syndrome (HUS). Bacterial virulence factors like subtypes of the Shiga toxin (Stx) and the locus of enterocyte effacement (LEE) pathogenicity island, as well as host factors like young age, are strongly associated with development of HUS. However, these factors alone do not accurately differentiate between strains that cause HUS and those that do not cause severe disease, which is important in the context of diagnosis, treatment, as well as infection control...
2018: Frontiers in Microbiology
Chih-Feng Wu, Delaney A Smith, Erh-Min Lai, Jeff H Chang
The bacterial type VI secretion system (T6SS) is a contractile nanomachine dedicated to delivering molecules out of bacterial cells. T6SS-encoding loci are in the genome sequences of many Gram-negative bacteria, and T6SS has been implicated in a plethora of roles. In the majority of cases, the T6SSs deliver effector proteins in a contact-dependent manner to antagonize other bacteria. Current models suggest that the effectors are deployed to influence social interactions in microbial communities. In this chapter, we describe the structure, function, and regulation of the T6SS and its effectors...
July 11, 2018: Current Topics in Microbiology and Immunology
Lixing Huang, Wenjia Liu, Qingling Jiang, Yanfei Zuo, Yongquan Su, Lingmin Zhao, Yingxue Qin, Qingpi Yan
Pseudomonas plecoglossicida is a facultative pathogen that is associated with diseases of multiple fish, mainly at 15-20°C. Although fish disease caused by P. plecoglossicida has led to significant economic losses, the mechanisms of the temperature-dependent virulence are unclear. Here, we identify potential pathogenicity mechanisms and demonstrate the direct regulation of several virulence factors by temperature with transcriptomic and proteomic analyses, quantitative real-time PCR (qRT-PCR), RNAi, pyoverdine (PVD) quantification, the chrome azurol S (CAS) assay, growth curve measurements, a biofilm assay, and artificial infection...
2018: Frontiers in Cellular and Infection Microbiology
David Fast, Benjamin Kostiuk, Edan Foley, Stefan Pukatzki
While the structure and regulatory networks that govern type-six secretion system (T6SS) activity of Vibrio cholerae are becoming increasingly clear, we know less about the role of T6SS in disease. Under laboratory conditions, V. cholerae uses T6SS to outcompete many Gram-negative species, including other V. cholerae strains and human commensal bacteria. However, the role of these interactions has not been resolved in an in vivo setting. We used the Drosophila melanogaster model of cholera to define the contribution of T6SS to V...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Lifan Wei, Yanyan Wu, Haoxian Qiao, Wensheng Xu, Yuanxing Zhang, Xiaohong Liu, Qiyao Wang
Edwardsiella piscicida is an infectious Gram-negative bacterium that causes great losses to the aquaculture industry worldwide. Based on pattern analysis of conditional essentiality (PACE), a new method for transposon insertion sequencing (Tn-seq) data analysis, we investigated the genome-wide genetic requirements during the dynamic process of infection and colonization in turbot in this study. As a result, disruption of ETAE_1437 was discovered to lead to substantially reduced colonization, which was similar to the in vivo dynamic patterns of the mutants of T3SS or T6SS...
July 1, 2018: FEMS Microbiology Letters
Qingmei Jia, Marcus A Horwitz
Francisella tularensis is the causative agent of tularemia and a Tier I bioterrorism agent. In the 1900s, several vaccines were developed against tularemia including the killed "Foshay" vaccine, subunit vaccines comprising F. tularensis protein(s) or lipoproteins(s) in an adjuvant formulation, and the F. tularensis Live Vaccine Strain (LVS); none were licensed in the U.S.A. or European Union. The LVS vaccine retains toxicity in humans and animals-especially mice-but has demonstrated efficacy in humans, and thus serves as the current gold standard for vaccine efficacy studies...
2018: Frontiers in Cellular and Infection Microbiology
Jingjing Pan, Meng Zhao, Yuanming Huang, Jing Li, Xiaoshu Liu, Zhihong Ren, Biao Kan, Weili Liang
Vibrio fluvialis , an emerging foodborne pathogen of increasing public health concern, contains two distinct gene clusters encoding type VI secretion system (T6SS), the most newly discovered secretion pathway in Gram-negative bacteria. Previously we have shown that one of the two T6SS clusters, namely VflT6SS2, is active and associates with anti-bacterial activity. However, how its activity is regulated is not completely understood. Here, we report that the global regulator integration host factor (IHF) positively modulates the expression and thus the function of VflT6SS2 through co-regulating its major cluster and tssD 2 -tssI 2 (also known as hcp-vgrG ) orphan clusters...
2018: Frontiers in Microbiology
Kayley H Janssen, Manisha R Diaz, Cindy J Gode, Matthew C Wolfgang, Timothy L Yahr
The Gram-negative opportunistic pathogen Pseudomonas aeruginosa has distinct genetic programs that favor either acute or chronic virulence gene expression. Acute virulence is associated with twitching and swimming motility, expression of a type III secretion system (T3SS), and the absence of alginate, Psl, or Pel polysaccharide production. Traits associated with chronic infection include growth as a biofilm, reduced motility, and expression of a type VI secretion system (T6SS). The Rsm post-transcriptional regulatory system plays important roles in the inverse control of phenotypes associated with acute and chronic virulence...
June 4, 2018: Journal of Bacteriology
Nannan Wang, Jin Liu, Maoda Pang, Yafeng Wu, Furqan Awan, Mark R Liles, Chengping Lu, Yongjie Liu
The type VI secretion system (T6SS) has been considered as a crucial factor in bacterial competition and virulence. The hemolysin co-regulated protein (Hcp) is the hallmark of T6SS. The secretion of Hcp in Aeromonas hydrophila Chinese epidemic strain NJ-35 indicated a functional T6SS. In this study, three copies of the hcp gene were identified in the genome of strain NJ-35. We targeted these Hcp family proteins for generating deletion mutants. These mutants showed varying levels in Hcp production, the interaction with other bacteria or eukaryotic cells, and bacterial virulence...
June 3, 2018: Applied Microbiology and Biotechnology
Pengpeng Li, Dongqing Xu, Tiequn Ma, Daoying Wang, Weidong Li, Jianhua He, Tingting Ran, Weiwu Wang
The type VI secretion system (T6SS) is a versatile and widespread export system found in many Gram-negative bacteria that delivers effector proteins into target cells. The functions of T6SSs are tightly regulated by diverse mechanisms at multiple levels, including posttranslational modification through threonine phosphorylation via the Ser/Thr protein kinase (STPK) PpkA. Here, we identified that PpkA is essential for T6SS secretion in Serratia marcescens since its deletion eliminated the secretion of hemolysin coregulated protein (Hcp), while the periplasmic and transmembrane portion of PpkA was found to be disposable for T6SS secretion...
June 1, 2018: Biochemical Journal
Vera Troselj, Daniel Wall
Bacteria in nature live in taxonomically complex communities where multitude of species and strains inhabit the same niches and compete for limited resources and space. Surviving in these competitive environments requires mechanisms to recognize and associate with kin and to discriminate against non-kin to increase reproductive success among close relatives. Some of the mechanisms bacteria use to address genetic differences are surface receptors, diffusible signals (e.g. quorum sensing) and toxin-immunity systems (e...
April 4, 2018: Microbial Cell
Xiaolong Shao, Xiaoning Zhang, Yingchao Zhang, Miao Zhu, Pan Yang, Jian Yuan, Yingpeng Xie, Tianhong Zhou, Wei Wang, Sheng Chen, Haihua Liang, Xin Deng
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen of humans, particularly those with cystic fibrosis. As a global regulator, RpoN controls a group of virulence-related factors and quorum sensing (QS) genes in P. aeruginosa To further gain insights into the direct targets of RpoN in vivo , the present study focused on identifying the direct targets of RpoN regulation in QS and the type VI secretion system (T6SS). We performed a chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-seq) assay that identified 1,068 binding sites of RpoN, mostly including metabolic genes, a group of genes in QS ( lasI , rhlI and pqsR ) and the T6SS ( hcpA and hcpB )...
May 14, 2018: Journal of Bacteriology
Daniel L Clemens, Bai-Yu Lee, Marcus A Horwitz
Francisella tularensisis subsp. tularensis is an intracellular bacterial pathogen and the causative agent of the life-threatening zoonotic disease tularemia. The Francisella Pathogenicity Island encodes a large secretion apparatus, known as a Type VI Secretion System (T6SS), which is essential for Francisella to escape from its phagosome and multiply within host macrophages and to cause disease in animals. The T6SS, found in one-quarter of Gram-negative bacteria including many highly pathogenic ones, is a recently discovered secretion system that is not yet fully understood...
2018: Frontiers in Cellular and Infection Microbiology
Timothy C Fitzsimons, Jessica M Lewis, Amy Wright, Oded Kleifeld, Ralf B Schittenhelm, David Powell, Marina Harper, John D Boyce
The Type VI Secretion System (T6SS) is a macromolecular machine that delivers protein effectors into host cells and/or competing bacteria. The effectors may be delivered as non-covalently bound cargo of T6SS needle proteins (VgrG/Hcp/PAAR) or as C-terminal extensions of these proteins. Many Acinetobacter baumannii strains produce a T6SS, but little is known about the specific effectors or how they are delivered. In this study, we show that A. baumannii AB307-0294 encodes three vgrG loci, each containing a vgrG gene, a T6SS toxic effector gene and an antitoxin/immunity gene...
May 7, 2018: Infection and Immunity
Xiaobing Yang, Mingxiu Long, Xihui Shen
Type VI protein secretion systems (T6SSs) are specialized transport apparatus which can target both eukaryotic and prokaryotic cells and play key roles in host⁻pathogen⁻microbiota interactions. Therefore, T6SSs have attracted much attention as a research topic during the past ten years. In this review, we particularly summarized the T6SS antibacterial function, which involves an interesting offensive and defensive mechanism of the effector⁻immunity (E⁻I) pairs. The three main categories of effectors that target the cell wall, membranes, and nucleic acids during bacterial interaction, along with their corresponding immunity proteins are presented...
April 26, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jiale Ma, Min Sun, Zihao Pan, Chengping Lu, Huochun Yao
The type VI secretion system (T6SS) is considered as one of the key competition strategies by injecting toxic effectors for intestinal pathogens to acquire optimal colonization in host gut, a microenviroment with high-density polymicrobial community where bacteria compete for niches and resources. Enterotoxigenic Escherichia coli (ETEC), a major cause of infectious diarrhea in human and animals, widely encode T6SS clusters in their genomes. In this report, we first identified VT1, a novel amidase effector in ETEC, significantly hydrolyzed D-lactyl-L-Ala crosslinks between N-acetylmuramoyl and L-Ala in peptidoglycan...
July 2018: Biochimica et Biophysica Acta
Rhishita Chourashi, Suman Das, Debarpan Dhar, Keinosuke Okamoto, Asish K Mukhopadhyay, Nabendu Sekhar Chatterjee
Vibrio cholerae regularly colonizes the chitinous exoskeleton of crustacean shells in the aquatic region. The type 6 secretion system (T6SS) in V. cholerae is an interbacterial killing device. This system is thought to provide a competitive advantage to V. cholerae in a polymicrobial community of the aquatic region under nutrient-poor conditions. V. cholerae chitin sensing is known to be initiated by the activation of a two-component sensor histidine kinase ChiS in the presence of GlcNAc2 (N,N'-diacetylchitobiose) residues generated by the action of chitinases on chitin...
May 2018: Microbiology
Brianne J Burkinshaw, Xiaoye Liang, Megan Wong, Alexander N H Le, Linh Lam, Tao G Dong
The type VI secretion system (T6SS) is used by many Gram-negative bacteria as a molecular weapon to modulate neighbouring bacterial and eukaryotic cells, thereby affecting the dynamics of community structure in multiple species environments. The T6SS injects its inner-needle Hcp tube, the sharpening tip complex consisting of VgrG and PAAR, and toxic effectors into neighbouring cells. Its functions are largely determined by the activities of its delivered effectors. Six mechanisms of effector delivery have been described: two mediated by the inner tube and the others mediated by the VgrG and PAAR tip complex...
May 2018: Nature Microbiology
Savannah L Logan, Jacob Thomas, Jinyuan Yan, Ryan P Baker, Drew S Shields, Joao B Xavier, Brian K Hammer, Raghuveer Parthasarathy
Host-associated microbiota help defend against bacterial pathogens; however, the mechanisms by which pathogens overcome this defense remain largely unknown. We developed a zebrafish model and used live imaging to directly study how the human pathogen Vibrio cholerae invades the intestine. The gut microbiota of fish monocolonized by symbiotic strain Aeromonas veronii was displaced by V. cholerae expressing its type VI secretion system (T6SS), a syringe-like apparatus that deploys effector proteins into target cells...
April 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
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