Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the heat shock response in the mouse pneumonitis strain of Chlamydia trachomatis. The kinetics of the chlamydial heat shock response resembled that of other procaryotes: the induction was rapid, occurring over a 5- to 10-min time period, and was regulated at the level of transcription. Immunoblot analysis and immunoprecipitations with heterologous antisera to the heat shock proteins DnaK and GroEL demonstrated that the rate of synthesis, but not the absolute amount of these two proteins, increased after heat shock. Using a general screen for genes whose mRNAs are induced by heat shock, we identified and cloned two of these. DNA sequence analysis demonstrated that one of the genes is a homolog of dnaK. Further sequence analysis of the region upstream of the dnaK gene revealed that the chlamydial homolog of the grpE gene is located just adjacent to the dnaK gene. The second locus encoded three potential nonoverlapping open reading frames. One of the open reading frames was 52% homologous to the ribosomal protein S18 of Escherichia coli and thus presumably encodes the chlamydial homolog. Interestingly, this ribosomal protein is not known to be induced by heat shock in E. coli. S1 nuclease and primer extension analyses located the start site of the dnaK transcript to the last nucleotide of the grpE coding sequence, suggesting that these two genes, although tandemly arranged, are transcribed separately. No promoter sequences resembling the E. coli consensus heat shock promoter could be identified upstream of either the C. trachomatis dnaK, grpE, or S18 gene. The induction of the dnaK and S18 mRNAs by heat shock occurred at a transcriptional level; their induction could be blocked by rifampin. The mechanisms of induction for these two loci were not the same, however; they were differentially sensitive to chloramphenicol. Whereas the induction of dnaK mRNA required de novo protein synthesis, the induction of the S18 mRNA did not. Thus, C. trachomatis utilizes at least two different pathways to induce the transcription of mRNAs encoding proteins induced in the heat shock response.
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PMID:Heat shock response of murine Chlamydia trachomatis. 225 67

Streptococcus pneumoniae is a major human pathogen that causes high mortality and morbidity rates and has developed resistance to many antibiotics. The genome of S. pneumoniae has recently been completely sequenced revealing many genes encoding hypothetical proteins of unknown function. We have found that the gene encoding one such conserved protein, SP14.3, is essential for growth of S. pneumonia. Since it is essential, SP14.3 represents a potential target for drug discovery. Here, we describe the three-dimensional solution structure of SP14.3 as determined by NMR spectroscopy. The structure consists of two domains each with an alpha/beta-fold. The N-terminal domain contains two alpha-helices and a three-stranded beta-sheet, while the C-terminal domain is composed of one alpha-helix and a five-stranded beta-sheet. The N-terminal domain of the protein contains a highly negatively charged surface and resembles the fold of the N-terminal domain of Thermus thermophilus ribosomal protein S3. The C-terminal domain has a protein fold similar to human small nuclear ribonucleoprotein Sm D3 and Haloarcula marismortui ribosomal protein L21E. The two domains of the protein tumble in solution overall as a whole with an overall molecular rotational correlation time (tau(m)) of 12.9 ns at 25 degrees C. The relative orientation of the two domains is not defined by the nuclear Overhauser effect data. Indeed, residual dipolar couplings and the structure calculations indicate that the relative orientation of the two domains is not rigidly oriented with respect to one another in solution.
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PMID:Solution structure and function of a conserved protein SP14.3 encoded by an essential Streptococcus pneumoniae gene. 1149 12

We evaluated the usefulness of a rapid antigen detection assay for L7/L12 ribosomal protein (Ribotest Mycoplasma; Asahi Kasei Pharma) for diagnosis of Mycoplasma pneumoniae (M. pneumoniae) infection. Nasopharyngeal swabs were obtained from patients with pneumonia and/or bronchitis; real-time PCR and the L 7/L12 antigen assays were performed with each sample. Serum was also taken from each patient, and the particle agglutination (PA) method was used to detect anti-M. pneumoniae antibody in these samples. Macrolide-resistance genes were detected and M. pneumoniae P1 protein subtyping was performed on PCR-positive samples. PCR assays were positive for 85 of 212 specimens (40.1%). Sensitivity and specificity of the L7/L12 antigen assays relative to the PCR standard were 74.1% (63/85) and 81.1% (103/127), respectively. For PCR-positive specimens with a large quantity of M. pneumoniae nucleic acid, sensitivity of the L7/L12 antigen assays seemed to be high. In PCR-positive specimens with fewer than 1.0 x 10(6) copies/mL of M. pneumoniae nucleic acid, sensitivity of the L7/L12 antigen assays seemed to be low. When the PA method was used as the standard, the relative sensitivity and specificity of the L7/L12 antigen assays were 41.7% (5/12) and 75.3% (58/77), respectively, for single serum and 60.9% (14/23) and 85.7% (18/21), respectively, for paired sera. The macrolide-resistance gene A2063G was detected in 20 of the 30 tested PCR-positive specimens (66.7%). Of these 20 A2063G-positive specimens, 13 (65.0%) were positive for the L7/L12 antigen assays. Tne numbers of M. pneumoniae P1 subtypes were as follows: types I (22), IIa(2), IIc(1), and untypable (5). The L7/L12 antigen assays gave positive results for 17 of 21 (81.0%) subtype I, 1 of 2 (50.0%) IIa, and 1 of 1(100%) IIc specimens.
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PMID:[Evaluation of a Rapid Antigen Detection Kit Targeting L7/L12 Ribosomal Protein for Mycoplasma pneumoniae]. 2655 32

Posttranscriptional gene regulation often involves RNA-binding proteins that modulate mRNA translation and/or stability either directly through protein-RNA interactions or indirectly by facilitating the annealing of small regulatory RNAs (sRNAs). The human pathogen Streptococcus pneumoniae D39 (pneumococcus) does not encode homologs to RNA-binding proteins known to be involved in promoting sRNA stability and function, such as Hfq or ProQ, even though it contains genes for at least 112 sRNAs. However, the pneumococcal genome contains genes for other RNA-binding proteins, including at least six S1 domain proteins: ribosomal protein S1 (rpsA), polynucleotide phosphorylase (pnpA), RNase R (rnr), and three proteins with unknown functions. Here, we characterize the function of one of these conserved, yet uncharacterized, S1 domain proteins, SPD_1366, which we have renamed CvfD (conserved virulence factor D), since loss of the protein results in attenuation of virulence in a murine pneumonia model. We report that deletion of cvfD impacts the expression of 144 transcripts, including the pst1 operon, encoding phosphate transport system 1 in S. pneumoniae We further show that CvfD posttranscriptionally regulates the PhoU2 master regulator of the pneumococcal dual-phosphate transport system by binding phoU2 mRNA and impacting PhoU2 translation. CvfD not only controls expression of phosphate transporter genes but also functions as a pleiotropic regulator that impacts cold sensitivity and the expression of sRNAs and genes involved in diverse cellular functions, including manganese uptake and zinc efflux. Together, our data show that CvfD exerts a broad impact on pneumococcal physiology and virulence, partly by posttranscriptional gene regulation.IMPORTANCE Recent advances have led to the identification of numerous sRNAs in the major human respiratory pathogen S. pneumoniae However, little is known about the functions of most sRNAs or RNA-binding proteins involved in RNA biology in pneumococcus. In this paper, we characterize the phenotypes and one target of the S1 domain RNA-binding protein CvfD, a homolog of general stress protein 13 identified, but not extensively characterized, in other Firmicutes species. Pneumococcal CvfD is a broadly pleiotropic regulator, whose absence results in misregulation of divalent cation homeostasis, reduced translation of the PhoU2 master regulator of phosphate uptake, altered metabolism and sRNA amounts, cold sensitivity, and attenuation of virulence. These findings underscore the critical roles of RNA biology in pneumococcal physiology and virulence.
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PMID:S1 Domain RNA-Binding Protein CvfD Is a New Posttranscriptional Regulator That Mediates Cold Sensitivity, Phosphate Transport, and Virulence in Streptococcus pneumoniae D39. 3260 Oct 68