Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of murine interferon-gamma (MuIFN-gamma) on the developmental cycle of Chlamydia trachomatis in McCoy cells was analyzed by light and electron microscopy. Addition to the culture media of 10 ng/ml of MuIFN-gamma, either 24 hr before or immediately after Chlamydia infection, resulted in a significant inhibition of the growth of this organism. Microscopic analysis showed that with both treatments the majority of microorganisms were arrested at the elementary body stage. Only a few small chlamydial inclusions were detected at 48 hr postinfection and contained predominately reticulate bodies. Furthermore, the growth of Chlamydia was arrested in cells that were treated with MuIFN-gamma at various intervals following infection. Addition of MuIFN-gamma at 8 or 12 hr after infection resulted in the arrest of chlamydial growth before initiation of reticulate body fission. When the MuIFN-gamma was added 24 hr postinfection, we could detect, by electron microscopy, inhibition at the stage of reticulate body replication.
Exp Mol Pathol 1987 Aug
PMID:Ultrastructural analysis of the anti-chlamydial activity of recombinant murine interferon-gamma. 311 77

The effect of two recombinant human hybrid interferons (IFNs), IFN-alpha AD (BglII) and IFN-alpha DA (BglII), on the growth cycle of Chlamydia trachomatis in a murine (McCoy) cell line was investigated. Ultrastructural analysis indicated that IFN-alpha AD inhibited the growth of chlamydia while IFN-alpha DA-treated cells did not significantly differ from the control monolayers. Treatment of the chlamydia-infected monolayers with IFN-alpha AD resulted in an inhibition in the transformation of elementary bodies to reticulate bodies with a consequent marked decrease in the number of chlamydia inclusions. Furthermore, chlamydial inclusions in the IFN-alpha AD-treated cells contained fewer and more immature chlamydial forms than the control or the IFN-alpha DA-treated cells. Secondary infection occurred in the IFN-alpha DA and in the control monolayer, but no such phenomena was detected in the IFN-alpha AD-treated McCoy cells indicating a loss of infectivity of the chlamydial organisms. From this study it can be concluded that purified recombinant human hybrid IFNs may exert an inhibitory effect on the growth cycle of C. trachomatis in a mouse cell line. This inhibition occurs primarily at the point of transformation from elementary to reticulate body.
Exp Mol Pathol 1984 Oct
PMID:Ultrastructural analysis of the growth cycle of Chlamydia trachomatis in mouse cells treated with recombinant human alpha-interferons. 647 93

The 18 kDa histone H1-like protein from Chlamydia trachomatis (Hc1) is a DNA-binding protein thought to be involved in condensation of the chlamydial chromosome during late stages in the chlamydial life cycle. Expression of Hc1 in Escherichia coli results in an overall relaxation of DNA and severely affects DNA, RNA and protein synthesis. We have analysed the interaction of Hc1 with single-stranded DNA and RNA by Southwestern and Northwestern blotting. Furthermore, we show that purified, recombinant Hc1 dramatically affects transcription and translation in vitro at physiologically relevant concentrations. These results were found to coincide with the formation of condensed Hc1-DNA and Hc1-RNA complexes as revealed by agarose gel electrophoresis and electron microscopy. The implications of these results for possible functions of Hc1 in vivo are discussed.
Mol Microbiol 1994 Mar
PMID:Interaction of the Chlamydia trachomatis histone H1-like protein (Hc1) with DNA and RNA causes repression of transcription and translation in vitro. 751 87

Chlamydiae possess a genus-specific epitope that is located on the lipopolysaccharide (LPS) and is composed of a 3-deoxy-D-manno-octulosonic acid (Kdo) trisaccharide of the sequence alpha Kdo-(2-->8)--alpha Kdo-(2-->4)-alpha Kdo. In Chlamydia trachomatis, this trisaccharide is biosynthetically generated through the action of a multi-functional Kdo-transferase encoded by the gene gseA. gseA of Chlamydia psittaci 6BC was cloned and expressed in a rough mutant (Re chemotype) of Escherichia coli (strain F515) that contains an LPS with only two alpha 2-->4-linked Kdo residues. Recombinant strains were able to add the immunodominant Kdo residue in alpha 2-->8-linkage to the parental LPS, as determined by SDS-PAGE and Western blot analysis using a monoclonal antibody against the genus-specific epitope. The DNA sequence of gseA was determined and aligned to that published recently for C. trachomatis serovar L2. Most surprisingly, the two deduced amino acid sequences shared only an overall homology of 67%. Thus, gseA exhibits species specificity at the DNA level, whereas its gene product results in the synthesis of a carbohydrate antigen with genus specificity.
Mol Microbiol 1993 Dec
PMID:The genus-specific lipopolysaccharide epitope of Chlamydia is assembled in C. psittaci and C. trachomatis by glycosyltransferases of low homology. 752 26

Immunophilins are housekeeping proteins present in a wide variety of organisms. Members of two protein superfamilies, cyclophilins (Cyps) and FK506-binding proteins (FKBPs) belong to this class of immunophilins. Despite the fact that the amino acid sequences of Cyp and FKBPs do not exhibit noticeable homology to each other, proteins of both classes are able to ligate immunosuppressive peptide derivatives. Cyps form complexes with the cyclic undercapeptide cyclosporin A and FKBPs are able to bind FK506 as well as rapamycin, both of which have a pipecolyl bond within their structure. In a ligand-bound form, immunophilins interfere with signal transduction in T cells. In addition, immunophilins have peptidyl prolyl cis-trans isomerase (PPlase) activity and are able to accelerate the rate of conformational events in proline-containing polypeptides. Microorganisms produce proteins that exhibit extensive sequence homologies to cyclophilins and FKBPs of higher organisms and which have considerable PPlase catalytic activity. While cyclophilins seem to be present in most if not all microbial species investigated, FKBPs are produced by yeasts as well as by a number of pathogenic bacteria, such as Legionella pneumophila, Chlamydia trachomatis and Neisseria meningitidis. The Mip protein of L. pneumophila is a virulence factor that plays an essential role in the ability of the bacteria to survive and multiply in phagocytic cells. Some results are summarized on the structure and putative functions of immunophilins and place special emphasis on the contribution of these polypeptides to the virulence of pathogenic microorganisms.
Mol Microbiol 1993 Nov
PMID:Immunophilins: structure-function relationship and possible role in microbial pathogenicity. 752 21

Trimethoprim and sulphisoxazole were used as selective agents in culture to isolate, by a stepwise procedure, a series of Chlamydia trachomatis L2 populations resistant to the cytotoxic effects of the drugs. Two trimethoprim-resistant populations, L2TriR-60 and L2TriR-100, and one sulphonamide-resistant population, L2SulfR-100, were characterized in more detail. In addition to being resistant to trimethoprim, L2TriR-60 was cross-resistant to methotrexate, sensitive to sulphisoxazole and displayed a ribonucleotide auxotrophy similar to that of its parental wild type, C. trachomatis L2. Surprisingly, L2TriR-100 and L2SulfR-100 appeared phenotypically identical. Both mutants were highly resistant to trimethoprim, sulphisoxazole, and methotrexate. In contrast to wild-type C. trachomatis L2, these populations were sensitive to 5-fluorouracil. L2TriR-100 and L2SulfR-100 were incapable of taking pyrimidine ribonucleotides from the host cell and no longer synthesized thymidine nucleotides de novo. The pyrimidine requirement of these mutants was met by salvaging host-cell uracil and thymidine, a property which can account for their drug-resistant characteristics. L2TriR-100 and L2SulfR-100 could also salvage adenine and guanine. Using L2TriR-100 as a starting stock, a mutant population resistant to the cytotoxic effects of trimethoprim and 5-fluorouracil (L2Tri/5-FU) was selected. L2Tri/5-FU was resistant to 5-fluorouracil because it had regained the capacity to take pyrimidine ribonucleotides from the host cell.
Mol Microbiol 1994 Oct
PMID:Characterization of trimethoprim- and sulphisoxazole-resistant Chlamydia trachomatis. 753 Mar 18

The Mip-like protein of Chlamydia trachomatis has sequence similarity with both the Mip protein of Legionella pneumophila, a virulence factor necessary for optimal intracellular infection, and FK506-binding proteins (FKBPs) of both prokaryotic and eukaryotic origin. FKBPs contain a site for peptidyl-prolyl cis/trans isomerase activity, which is blocked upon binding of the drugs, FK506 or rapamycin. In this paper we report that the recombinant chlamydial Mip-like protein exhibits a peptidyl-prolyl cis/trans isomerase activity which is inhibited by either rapamycin or FK506. To assess the role of the Mip-like protein in chlamydial infection, rapamycin or FK506 (25 microM), were used in either treatment of chlamydial organisms prior to inoculation, or were present at different intervals through the infection. Pretreatment of organisms alone reduced infectivity for McCoy cells by 30%, with inhibition rising to 80% on more prolonged exposure from 0 to 8h and 8 to 16h post-inoculation and declining thereafter. When drug was present during the developmental cycle at intervals from 0 to 24h post-inoculation abnormal chlamydiae were induced in residual inclusions. The results suggest that inhibition of the isomerase of the Mip-like protein interferes with one or more early events in the infective process that determine productive intracellular infection.
Mol Microbiol 1993 Mar
PMID:Chlamydia trachomatis Mip-like protein has peptidyl-prolyl cis/trans isomerase activity that is inhibited by FK506 and rapamycin and is implicated in initiation of chlamydial infection. 768 81

We analysed transcription of the DNA region immediately downstream of the origin of replication in the chlamydial plasmid pCT. This region comprises two convergent open reading frames (ORF7, ORF8), encoding putative polypeptides that are homologous to each other and with C-terminal domains typical of the phage integrase family of proteins. Northern blot and RNA 5' end mapping analyses indicated that both ORFs were transcribed in the late phase of the chlamydial replicative cycle. RNA mapping showed the presence of a transcript starting 31 nucleotides (nt) before the ATG start codon of ORF7, and two temporally regulated transcripts starting 59 and 89 nt upstream of the ATG start codon of ORF8. Two abundant RNA species of 225 and 415 nt were also identified as overlapping anti-sense transcripts (AS-RNAs), complementary to the 3' end of ORF8 mRNA, with identical 5' ends but different 3' ends. In vitro and in vivo experiments in Escherichia coli showed that the sigma 70-RNA polymerase complex was capable of initiating RNA synthesis at the same sites as observed in Chlamydia trachomatis for ORF7 and AS-RNA transcripts, but was not able to transcribe ORF8. In accord with this, sequences at -10 and -35 nt upstream of the RNA 5' ends resemble sigma 70 consensus promoters in the case of ORF7 and AS, but not in the case of the two ORF8 transcripts. Therefore, transcription of ORF7 and ORF8 is controlled by different types of promoters.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Gen Genet 1993 Mar
PMID:Transcriptional analysis of the Chlamydia trachomatis plasmid pCT identifies temporally regulated transcripts, anti-sense RNA and sigma 70-selected promoters. 768 69

Chlamydiae are obligate intracellular bacteria which occupy a non-acidified vacuole (the inclusion) throughout their developmental cycle. Little is known about events leading to the establishment and maintenance of the chlamydial inclusion membrane. To identify chlamydial proteins which are unique to the intracellular phase of the life cycle, an expression library of Chlamydia psittaci DNA was screened with convalescent antisera from infected animals and hyperimmune antisera generated against formalin-killed purified chlamydiae. Overlapping genomic clones were identified which expressed a 39 kDa protein only recognized by the convalescent sera. Sequence analysis of the clones identified two open reading frames (ORFs), one of which (ORF1) coded for a predicted 39 kDa gene product. The ORF1 sequence was amplified and fused to the malE gene of Escherichia coli and antisera were raised against the resulting fusion protein. Immunoblotting with these antisera demonstrated that the 39 kDa protein was present in lysates of infected cells and in reticulate bodies (RBs), but was at the limit of detection in lysates of purified C. psittaci elementary bodies. Fluorescence microscopy experiments demonstrated that this protein was localized in the inclusion membrane of infected HeLa cells, but was not detected on the developmental forms within the inclusion. Because the protein produced by ORF1 is deposited on the inclusion membrane of infected cells, this gene has been designated incA, (inclusion membrane protein A) and its gene product, IncA. In addition to the inclusion membrane, these antisera labelled structures that extended from the inclusion over the nucleus or into the cytoplasm of infected cells. Immunoblotting also demonstrated that IncA, in lysates of infected cells, had a migration pattern that seemed indicative of post-translational modification. This pattern was not observed in immunoblots of RBs or in the E. coli expressing IncA. Collectively, these data identify a chlamydial gene which codes for a protein that is released from RB and is localized in the inclusion membrane of infected cells.
Mol Microbiol 1995 Feb
PMID:Cloning and characterization of a Chlamydia psittaci gene coding for a protein localized in the inclusion membrane of infected cells. 778 34

We have examined the relationship between Chlamydia trachomatis found in clinical samples in which the cryptic plasmid was absent and known serovars of C. trachomatis. PCR and RNase protection assays were used to compare 12 C. trachomatis serovars and a plasmidless L2 serovar strain with the reactivity of clinical specimens taken from patients with pelvic inflammatory disease (PID) containing the C. trachomatis 16S rRNA gene and 16S rRNA but lacking plasmid DNA. Serovars D, E, H and I were unreactive in either or both of the PCR and RNase protection assays. The plasmidless L2 strain had reactivities indistinguishable from the nucleic acids found in the PID clinical specimens. Serovar D, the plasmidless L2 strain, and nucleic acids from two of the PID specimens were further compared by amplifying, cloning and sequencing the 16S rRNA genes detected in these samples. The sequences of the 16S rRNA genes detected in the PID clinical samples and the 16S rRNA gene of the plasmidless C. trachomatis variant were indistinguishable from previously reported sequences of the C. trachomatis 16S rRNA. Serovar D showed five base changes over the same region. We conclude that although these clinical samples lack the C. trachomatis cryptic plasmid, they do contain C. trachomatis nucleic acid.
Mol Cell Probes 1994 Oct
PMID:Molecular cloning and nucleic acid sequencing of Chlamydia trachomatis 16S rRNA genes from patient samples lacking the cryptic plasmid. 787 40


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>