The Vibrio cholerae MARTX toxin silences the inflammatory response to cytoskeletal damage before inducing actin cytoskeleton collapse.

The Vibrio cholerae MARTX toxin silences the inflammatory response to cytoskeletal damage before inducing actin cytoskeleton collapse. Sci Signal. 2020 Jan 14;13(614): Authors: Woida PJ, Satchell KJF Abstract Multifunctional autoprocessing repeats-in-toxin (MARTX) toxins are pore-forming bacterial toxins that translocate multiple functionally independent effector domains into a target eukaryotic cell. Vibrio cholerae colonizes intestinal epithelial cells (IECs) and uses a MARTX toxin with three effector domains-an actin cross-linking domain (ACD), a Rho inactivation domain (RID), and an α/β hydrolase domain (ABH)-to suppress innate immunity and enhance colonization. We investigated whether these multiple catalytic enzymes delivered from a single toxin functioned in a coordinated manner to suppress intestinal innate immunity. Using cultured human IECs, we demonstrated that ACD-induced cytoskeletal collapse activated extracellular signal-regulated kinase, p38, and c-Jun amino-terminal kinase mitogen-activated protein kinase (MAPK) signaling to elicit a robust proinflammatory response characterized by the secretion of interleukin-8 (IL-8; also called CXCL8) and the expression of CXCL8, tumor necrosis factor (TNF), and other proinflammatory genes. However, RID and ABH, which are naturally delivered together with ACD, blocked MAPK activation through Rac1 and thus prevented ACD-induced inflammation. RID also abolished IL-8 secretion induced by heat-...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research

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[AIM] Maputo -The Mozambican health authorities have declared a cholera outbreak in three districts in the northern province of Cabo Delgado - namely Macomia, Mocimboa da Praia and Ibo.
Source: AllAfrica News: Health and Medicine - Category: African Health Source Type: news
Since the English physician John Snow first mapped London ’s cholera outbreak to a local water pump in the 1850s, it has been understood that a community’s design affects the health of its inhabitants. Present-day research continues to support a dominant role for place-based factors in generating health outcomes, but investment in local drivers of heal th has not kept pace with our understanding of their outsize influence on morbidity and mortality.
Source: JAMA - Category: General Medicine Source Type: research
Abstract Grass carp reovirus (GCRV) is one of the most serious pathogens threatening grass carp (Ctenopharyngodon idella) production and results in high mortality in China. To obtain a genetically engineered oral vaccine against GCRV, the cholera toxin B subunit (CTB) of Vibrio cholerae was fused to VP7 (CTB-VP7) and transformed into BL21(DE3) for expression. SDS-PAGE and Western blotting showed that the purified rCTB-VP7 fusion protein (rCTB-VP7) was approximately 49.0 kDa. The monomeric nature of rCTB-VP7 through multistage purification showed a binding affinity for GM1, a receptor for biologically active CTB....
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Tags: Int J Biol Macromol Source Type: research
TTP, a technology company based in Melbourn, UK, is developing a handheld PCR (polymerase chain reaction) diagnostic device that can rapidly detect influenza viruses, and one day other viruses, in samples of nasal mucus. The company claims that the s...
Source: Medgadget - Category: Medical Devices Authors: Tags: Diagnostics Exclusive Public Health Source Type: blogs
In this report, we investigated six RND efflux-responsive regulatory genes for contributions to V. cholerae virulence factor production. Our data showed that the V. cholerae gene VC2714, encoding a homolog of Escherichia coli OmpR, was a virulence repressor. The expression of ompR was elevated in an RND-null mutant, and ompR deletion partially restored virulence factor production in the RND-negative background. Virulence inhibitory activity in the RND-negative background resulted from OmpR repression of the key ToxR regulon virulence activator aphB, and ompR overexpression in wild-type cells also repressed virulence throug...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Molecular Pathogenesis Source Type: research
In this study, we found that another key virulence regulator, ToxR, was important for V. cholerae resistance to hydrogen peroxide. Through a genome-wide transposon screen, we discovered that a deletion in mneA, which encodes a manganese exporter, restored ROS resistance of the toxR mutant. We then showed that ToxR did not affect mneA transcription but that the ToxR-regulated major porin OmpU was critical for ROS resistance. The addition of manganese in culture medium restored ROS resistance in both the toxR and ompU mutants. Furthermore, elemental analysis indicated that the intracellular concentration of manganese in both...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Molecular Pathogenesis Source Type: research
el Moss Arginine-specific mono-adenosine diphosphate (ADP)-ribosylation is a nicotinamide adenine dinucleotide (NAD)+-dependent, reversible post-translational modification involving the transfer of an ADP-ribose from NAD+ by bacterial toxins and eukaryotic ADP-ribosyltransferases (ARTs) to arginine on an acceptor protein or peptide. ADP-ribosylarginine hydrolase 1 (ARH1) catalyzes the cleavage of the ADP-ribose-arginine bond, regenerating (arginine)protein. Arginine-specific mono-ADP-ribosylation catalyzed by bacterial toxins was first identified as a mechanism of disease pathogenesis. Cholera toxin ADP-ribosylates and...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
[MSF] MSF has been providing healthcare in Cabo Delgado province, one of the poorest and most isolated regions of Mozambique, since February 2019. Early activities were rapidly disrupted by Cyclone Kenneth in late April 2019, and replaced with emergency response to displacement and cholera. Since then, MSF has been building up healthcare activities. Bruno Cardoso, MSF's project coordinator, has just returned from Mozambique and tells us more about the situation and what MSF does there.
Source: AllAfrica News: Health and Medicine - Category: African Health Source Type: news
In 1817 there was a major outbreak of cholera in India that spread to Asia and Europe. The disease reached England in 1831, and war in America and Europe helped its spread. Here the author describes the bacteriology, pathogenesis, diagnosis, treatment and prevention of this notifiable disease.
Source: Trends in Urology and Men's Health - Category: Urology & Nephrology Authors: Tags: Infections Source Type: research
Abstract Type III secretion systems (T3SS) can be found in many pathogenic bacteria, such as Dysentery bacillus, Salmonella typhimurium, Vibrio cholera and pathogenic Escherichia coli. The routes of infection of these bacteria include the T3SS transferring a large number of type III secreted effectors (T3SE) into host cells, thereby blocking or adjusting the communication channels of the host cells. Therefore, the accurate identification of T3SEs is the precondition for the further study of pathogenic bacteria. In this article, a new T3SEs ensemble predictor was developed, which can accurately distinguish T3SEs fr...
Source: Briefings in Bioinformatics - Category: Bioinformatics Authors: Tags: Brief Bioinform Source Type: research
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