Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HTLV-1-infection is associated with a variety of human diseases including adult T-cell leukemia (ATL) and non-neoplastic inflammatory diseases. The latter includes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 uveitis (HU) and other diseases with unestablished associations such as arthropathy, pneumopathy, dermatitis, exocrinopathy and myositis. ATL is defined as neoplastic clonal growth of HTLV-1-infected T-cells and is characterized by unique clinical features including hypercalcemia and severe organ infiltration of leukemic cells. HAM/TSP and HU are characterized by infiltration of HTLV-1-infected lymphocytes and dysregulated production of cytokines. Four major subtypes (genotypes) of HTLV-1 have been identified, which depend more on geography than disease. No disease-specific variants or mutations have been identified to date. A viral transcriptional regulator, Tax, regulates virus and cellular gene expression through binding to transcription factors or other cytoplasmic cellular molecules. Aberrant expression of cellular genes will affect fundamental cellular functions. The interaction between HTLV-1-infected cells and different kinds of cells in the host appears to be one of the basic mechanisms underlying the development of HTLV-1-associated diseases. This interaction may play a major role in determining tumorigenicity and in forming clinical features of the disease. Increased provirus load found in patients with HAM/TSP and HU results from clonal expansion of the HTLV-1-infected T-cells, which has been implicated in the pathogenesis of HTLV-1-associated diseases. Regulatory mechanisms of clonal growth remain unknown. Efforts to characterize functions of the viral proteins and the virus-infected cells and to understand the natural history of the HTLV-1-infection are required to determine the mechanisms of HTLV-1 viral pathogenesis.
 ...
PMID:HTLV-1-associated diseases. 940 Dec 72

Transcriptional regulatory networks are fundamental to how microbes alter gene expression in response to environmental stimuli, thereby playing a critical role in bacterial pathogenesis. However, understanding how bacterial transcriptional regulatory networks function during host-pathogen interaction is limited. Recent studies in group A Streptococcus (GAS) suggested that the transcriptional regulator catabolite control protein A (CcpA) influences many of the same genes as the control of virulence (CovRS) two-component gene regulatory system. To provide new information about the CcpA and CovRS networks, we compared the CcpA and CovR transcriptomes in a serotype M1 GAS strain. The transcript levels of several of the same genes encoding virulence factors and proteins involved in basic metabolic processes were affected in both DeltaccpA and DeltacovR isogenic mutant strains. Recombinant CcpA and CovR bound with high-affinity to the promoter regions of several co-regulated genes, including those encoding proteins involved in carbohydrate and amino acid metabolism. Compared to the wild-type parental strain, DeltaccpA and DeltacovRDeltaccpA isogenic mutant strains were significantly less virulent in a mouse myositis model. Inactivation of CcpA and CovR alone and in combination led to significant alterations in the transcript levels of several key GAS virulence factor encoding genes during infection. Importantly, the transcript level alterations in the DeltaccpA and DeltacovRDeltaccpA isogenic mutant strains observed during infection were distinct from those occurring during growth in laboratory medium. These data provide new knowledge regarding the molecular mechanisms by which pathogenic bacteria respond to environmental signals to regulate virulence factor production and basic metabolic processes during infection.
 ...
PMID:A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection. 2033 40

Streptococcus pyogenes is a strict human pathogen responsible for more than 700 million infections annually worldwide. Strains of serotype M28 S. pyogenes are typically among the five more abundant types causing invasive infections and pharyngitis in adults and children. Type M28 strains also have an unusual propensity to cause puerperal sepsis and neonatal disease. We recently discovered that a one-nucleotide indel in an intergenic homopolymeric tract located between genes Spy1336/R28 and Spy1337 altered virulence in a mouse model of infection. In the present study, we analyzed size variation in this homopolymeric tract and determined the extent of heterogeneity in the number of tandemly-repeated 79-amino acid domains in the coding region of Spy1336/R28 in large samples of strains recovered from humans with invasive infections. Both repeat sequence elements are highly polymorphic in natural populations of M28 strains. Variation in the homopolymeric tract results in (i) changes in transcript levels of Spy1336/R28 and Spy1337 in vitro, (ii) differences in virulence in a mouse model of necrotizing myositis, and (iii) global transcriptome changes as shown by RNAseq analysis of isogenic mutant strains. Variation in the number of tandem repeats in the coding sequence of Spy1336/R28 is responsible for size variation of R28 protein in natural populations. Isogenic mutant strains in which genes encoding R28 or transcriptional regulator Spy1337 are inactivated are significantly less virulent in a nonhuman primate model of necrotizing myositis. Our findings provide impetus for additional studies addressing the role of R28 and Spy1337 variation in pathogen-host interactions.
 ...
PMID:Genetic heterogeneity of the Spy1336/R28-Spy1337 virulence axis in Streptococcus pyogenes and effect on gene transcript levels and pathogenesis. 3221 38