Disease relevance of virK

• The virulence plasmid pWR100 and the repertoire of proteins secreted by the type III secretion apparatus of Shigella flexneri [1].
• Expression of virK in Escherichia coli using a T7 RNA polymerase-dependent promoter system yielded a 36 kDa protein [2].
• The association of axenically grown trophozoites of Entamoeba histolytica strains HK-9 or HM-1:IMSS with various types of gram-negative bacteria for relatively short periods markedly increased their virulence, as evidenced by their ability to destroy monolayers of tissue-cultured cells [3].
• INTERPRETATION: The TTSS is a central virulence factor of diarrhoea-causing bacteria such as shigella, salmonella, and enteropathogenic Escherichia coli, which cause gastroenteritis by invading or intimately interacting with intestinal epithelial cells [4].
• Inorganic polyphosphate is essential for long-term survival and virulence factors in Shigella and Salmonella spp [5].

Psychiatry related information on virK

• This life style requires a sophisticated anti-host strategy, which is implemented by the Yersinia virulence plasmid [6].
• Although the common mucosal immune system has generally been considered to have only short-term memory, recent data suggest that long-term memory exists for Shigella virulence plasmid antigens [7].

High impact information on virK

• We have identified a region (virG) on the 230 kb virulence plasmid of S. flexneri that is required for cell-to-cell spread of the bacterium [8].
• Sequences hybridizing to this region were found in all intact virulence plasmids of Shigellae and enteroinvasive E. coli [8].
• This downregulation of immediate defense effectors might promote bacterial adherence and invasion into host epithelium and could be an important virulence parameter [9].
• DNA supercoiling and environmental regulation of virulence gene expression in Shigella flexneri [10].
• A number of environmental stresses (such as osmotic shock and anaerobiosis) have been shown to induce changes in DNA supercoiling that can directly affect the transcription of a specific subset of bacterial genes, at least some of which (the outer-membrane porins and type 1 fimbriae) play a part in bacterial virulence [10].

Chemical compound and disease context of virK

• The virulence factor IpgD, delivered into nonphagocytic cells by the type III secretion system of the pathogen Shigella flexneri, is a phosphoinositide 4-phosphatase generating phosphatidylinositol 5 monophosphate (PtdIns5P) [11].
• Lipopolysaccharide, particularly the O-antigen component, is one of many virulence determinants necessary for Shigella flexneri pathogenesis [12].
• The gene responsible for a nonstoichiometric alpha-1,7-linked N-acetylglucosamine substituent in the heptose (inner core) region was identified on the large virulence plasmids of E. coli O157 and Shigella flexneri serotype 2a [13].
• Genes encoding the synthesis and transport of aerobactin, a hydroxamate siderophore associated with increased virulence of enteric bacteria, were mapped within a pathogenicity island in Shigella flexneri [14].
• It is shown that Shigella flexneri maintains genetic control over the modal chain length of the O-antigen polysaccharide chains of its lipopolysaccharide (LPS) molecules because such a distribution is required for virulence [15].

Biological context of virK

• Expression of these functions requires the Mxi-Spa type III secretion apparatus and the secreted IpaA-D proteins, all of which are encoded by a virulence plasmid [1].
• The virulence traits of these pathogens include their ability to enter into epithelial cells and induce apoptosis in macrophages [1].
• Complete DNA sequence and analysis of the large virulence plasmid of Shigella flexneri [16].
• In the complete sequence of the virulence plasmid, 286 open reading frames (ORFs) were identified [16].
• Fifty putative proteins show no significant homology to proteins of known function; of these, 18 have a G+C content of less than 40%, typical of known virulence genes on the plasmid [16].

Anatomical context of virK

• The transductants all simultaneously became deregulated for virulence and invaded HeLa cells equally well at 30 degrees C and 37 degrees C. Other virulence-associated phenotypes were also deregulated and expressed at 30 degrees C. Southern hybridization with a probe for Tn10 determined the insertion to be on the chromosome [17].
• The median lethal dose and infection kinetics in mice suggest that the toxin is required for virulence and facilitates Salmonella survival within mouse peritoneal macrophages [18].
• The type III secretion (TTS) pathway is used by numerous Gram-negative pathogens to inject virulence factors into eukaryotic cells [19].
• The mutation, previously shown to compromise urinary tract virulence, was located within a 1112 bp gene that restored normal swarming of the mutant when expressed in trans [20].
• In contrast, the MreB system is required for establishment of the rod shape of the cell and for polar targeting of other polar constituents, such as the Shigella virulence factor IcsA and the aspartate chemoreceptor Tar, in a process that is independent of the Min system [21].

Associations of virK with chemical compounds

• Virulence of Entamoeba histolytica trophozoites. Effects of bacteria, microaerobic conditions, and metronidazole [3].
• Interaction of trophozoites with bacteria that were heat inactivated, glutaraldehyde fixed, or disrupted by sonication, or bacteria treated with inhibitors of protein synthesis, did not augment amebic virulence [3].
• In some of these mutants lacking ppk, the phenotypes included features indicative of decreased virulence such as: (i) growth defects, (ii) defective responses to stress and starvation, (iii) loss of viability, (iv) polymyxin sensitivity, (v) intolerance to acid and heat, and (vi) diminished invasiveness in epithelial cells [5].
• We showed that S. flexneri has two functional msbB genes, one carried by the chromosome (msbB1) and the other by the virulence plasmid (msbB2), the products of which act in complement to produce full acyl-oxy-acylation of the myristate at the 3' position of the lipid A glucosamine disaccharide [22].
• The 50 mutants were characterized with respect to their virulence phenotypes, including three different mutations that affect invasion of epithelial cells, bacterial metabolism and structure of lipopolysaccharide [23].

Regulatory relationships of virK

• H-NS, one of the main nucleoid-associated proteins, controls the temperature-dependent expression of the virulence genes by repressing the in vivo transcription of virF only below a critical temperature (approximately 32 degrees C) [24].
• It acts as a transcriptional activator and is itself transcriptionally activated by another virulence protein, VirF [25].

Other interactions of virK

• icsB: a Shigella flexneri virulence gene necessary for the lysis of protrusions during intercellular spread [26].
• Identification of a novel virulence gene, virA, on the large plasmid of Shigella, involved in invasion and intercellular spreading [27].
• The S. flexneri cytotoxic genes have been localized to the ipa operon of shigella's virulence plasmid. ipaB, C and D deletion mutants are not invasive and therefore not cytotoxic [28].
• Using TnphoA mutagenesis, we have identified two virulence plasmid genes, mxiJ and mxiM, that encode proteins exported by the general export pathway [29].
• Recombinant plasmids carrying this regulatory gene, designated ipaR, were found to restore full virulence to a non-invasive ipaR::Tn5 insertion mutant [M90T-W(pHS1042)] that had lost the ability to synthesize four Ipa antigens (IpaA, 70 kDa; IpaB, 62 kDa; IpaC, 42 kDa; and IpaD, 37 kDa) [30].

Analytical, diagnostic and therapeutic context of virK

• The complete sequence analysis of the 210-kb Shigella flexneri 5a virulence plasmid was determined [16].
• Plant bioassays showed that these mutants were significantly reduced in virulence, demonstrating both the presence of novel pathogenicity determinants in Eca, and the impact of functional genomics in expanding our understanding of phytopathogenicity in the Enterobacteriaceae [31].
• Molecular dissection of VirB, a key regulator of the virulence cascade of Shigella flexneri [32].
• Molecular cloning and characterization of chromosomal virulence region kcpA of Shigella flexneri [33].
• DNA hybridization and PCR demonstrated that eatA resides on the 92-kDa pCS1 virulence plasmid of H10407 and that it is present in multiple clinical ETEC strains [34].

References