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T F Meyer

Publications and source records attributed to T F Meyer.

At least 163 records · Page 9Linked to original sources
PubMed1989

[Pathogenic neisseriae--model of bacterial virulence and genetic flexibility].

The early stages of an infection with pathogenic Neisseriae are determined by receptor-mediated events that finally lead to the attachment and invasion of human mucous tissues. The factors participating in this process, the pili, OPA proteins, and perhaps lipopolysaccharide (LPS), are subject to complex genetic changes that enable the pathogens to produce multiple variant forms of these factors. Antigenic variation of the pathogenic Neisseriae permits both, the escape from the human immune response and the interaction with different cells and tissues of the human host. One of the intrinsic mechanisms of antigenic variation, i.e. genetic transformation, allows exchange and recombination of virulence genes between independent Neisseria strains in multiply infected individuals. Factors, such as IgA protease, alpha-factor, and the meningococcal capsule are attributed with further striking properties, and thus render the pathogenic Neisseriae as an excellent model for the investigation of bacterial virulence.

Antigenic Variation↗
PubMed1987

Molecular principles of antigenic variation in Neisseria gonorrhoeae.

The genome of Neisseria gonorrhoeae harbours many gene loci for the production of variant pili. Strain MS11 has two expression genes (pilE) with promoter and complete coding sequences. The remaining genes are silent (pilS) lacking the promoter and the conservative amino terminals coding sequences of pilin. The pilus genes consist of six variable minicassettes (mc's), that are flancked by strictly conserved sequences. Upon phase (P+ to P+) and antigenic (P+ to P-, or vice versa) transitions minicassettes from silent loci are transferred from silent pilus gene copies to the expression gene by gene conversion. P- variants resulting from such rearrangements still produce pilin mRNA as well as pilin, but only a few are found on the surface of those gonococci.

Antigenic Variation↗
PubMed1987

The control mechanism of opacity protein expression in the pathogenic Neisseriae.

The expression of Neisseria gonorrhoeae opacity protein shows frequent phase transitions. The genome contains at least twelve copies of the opa gene. Each copy is complete and different from most of the others in certain hypervariable regions. All opa genes are constitutively transcribed. Part of the leader peptide of all Op's is encoded by repetitive CTTCT pentameric units, the so-called coding repeat (CR). The number of repeat units found in the genes and mRNA is subject to frequent and precise changes. Such changes affect the expression of individual opa genes at the translational level. This control mechanism is common also to the class 5 proteins of N. meningitidis and the Op-related proteins of N. lactamica.

Antigens, Bacterial↗
PubMed1987

Neisseria gonorrhoeae IgA protease. Secretion and implications for pathogenesis.

A cloned 5 kb DNA fragment from Neisseria gonorrhoeae strain MS11 promotes expression and excretion of IgA protease in E. coli and other Gram-negative hosts. DNA sequencing reveals a large open reading frame coding for a precursor molecule of 169 kd. The 106 kd mature IgA protease is released from the bacteria in conjunction with a 15 kd soluble precursor segment, the alpha-protein. In contrast, the carboxy terminal portion of the precursor, the beta-protein (45 kd), remains associated with the outer bacterial membrane. The three proteins result form autoproteolytic cleavage at sites in the precursor which are similar to the target site in IgA1. Consensus sequences of the specific cleavage sites are found in a number of relevant human proteins. IgA protease may therefore have other natural substrates besides IgA1. The soluble alpha-protein as well as the membrane bound beta-protein, both associated with IgA protease, may confer additional virulence functions to the gonococcus.

Amino Acid Sequence↗
PubMed1987

Release of soluble pilin antigen coupled with gene conversion in Neisseria gonorrhoeae.

Gene conversion appears to be the frequent mechanism in Neisseria gonorrhoeae that leads to an altered expression of pilin, the subunit component of the pili. In this process segments of variable sequence information, the minicassettes, are transferred from silent storage loci into an expression locus. As a putative consequence of the rearrangement in the pilE gene, gonococci can enter a different phase of pilin production. Although the removal of a 7-amino acid leader peptide results in the production of typical P+ pilin used to form pili, the loss of an additional 39 amino acids yields S-pilin, a soluble form of pilin that is efficiently secreted into the extracellular environment. Both pilin types can coexist in an apparently homogeneous culture. Ps cells usually are piliated, although less extensively with regard to the length and the number of the pili when compared with P+ cells. Ps cells form T3/T4-type colonies also typical of nonpiliated cells (P-). The observations further suggest that the classical nonsecretory P- phenotype is not generated as a rule by precise gene conversion but rather by genetic changes that cause the production of an over-length pilin (L-pilin).

Amino Acid Sequence↗
PubMed1987

Common mechanism controlling phase and antigenic variation in pathogenic neisseriae.

The expression of the Neisseria gonorrhoeae opacity protein (Op, protein II), a major antigenic determinant of the outer membrane, is subject to frequent phase transitions. At least nine expression loci (opaE) are involved in the production of a large number of serologically distinct Op types. Using opa-specific oligonucleotides as probes in genomic blots, we detect Op-related gene sequences (opr) in N. meningitidis as well as in N. lactamica. DNA sequence analysis of such opr genes derived from N. meningitidis reveals distinct regions of homology with gonococcal opa E genes. As shown in the immunoblot, the proteins encoded by opa and opr are serologically related. Like the opaE genes, the 5'-coding sequences of the opr genes include a repetitive sequence composed of pentameric CTCTT units. The number of these coding repeat (CR) units is variable. This finding, together with the observation that all opr genes are constitutively transcribed, regardless of the status of protein production, suggests a translational control mechanism identical to that of the opa genes in gonococci. The related structures and control mechanisms of opa and opr genes imply a general significance of their gene products for the pathogenic character of the investigated Neisseria species.

Amino Acid Sequence↗
PubMed1986

Opacity genes in Neisseria gonorrhoeae: control of phase and antigenic variation.

The chromosome of N. gonorrhoeae contains several complete expression genes coding for variant opacity proteins. DNA sequence analysis of two opacity genes derived from the same locus (opaE1) of two isogenic gonococcal variants reveals common and variable regions in these genes. Genomic blotting experiments using synthetic probes suggest gene conversion as a principle for the assembly of variant sequence information in opacity genes. The 5' region of opacity genes is composed of identical pentameric pyrimidine units (CTCTT) encoding the hydrophobic portion of the opacity leader peptide. This coding repeat is variable in a given locus with respect of the number of pentameric units. While all expression loci in a single cell are constitutively transcribed, the production of opacity proteins is determined by the coding repeat sequence on the translational level.

Amino Acid Sequence↗
PubMed1986

The repertoire of silent pilus genes in Neisseria gonorrhoeae: evidence for gene conversion.

To investigate the significance of silent gene loci for pilus antigenic variation in N. gonorrhoeae, we determined the nucleotide sequence of the major silent locus, pilS1. The pilS1 locus contains six tandem pilus gene copies linked by a 39 bp repeat sequence also present in the expression loci. All silent copies lack the common N-terminal coding sequence of pilin, containing instead variant sequence information that constitutes a semivariable (SV) and a hypervariable (HV) domain. The SV and HV domains are interspersed with short, strictly conserved (C) regions flanking small cassettes of variable sequence information. It appears that such minicassettes from silent copies can be duplicated and transferred to other silent or expression genes by means of gene conversion.

Amino Acid Sequence↗
PubMed1986

Nucleotide sequence of ompV, the gene for a major Vibrio cholerae outer membrane protein.

The nucleotide sequence of the ompV gene of Vibrio cholerae was determined. The product of the gene is a 28,000 dalton protein which, after the removal of a 19 amino acid signal sequence, produces a mature outer membrane protein of 26,000 daltons. The cleavage site was determined by amino-terminal amino acid sequencing of the purified mature protein. The DNA upstream of the gene shows the presence of a typical promoter region as judged from the Escherichia coli consensus information; however, the Shine-Dalgarno sequence is associated with a region capable of forming a secondary structure in the mRNA. The formation of this structure would inhibit binding of the mRNA to the ribosome and reduce translation. It is proposed that this structure is recognized by a positive activator in V. cholerae and because of its absence in E. coli ompV is poorly expressed. The distribution of rare codons within ompV suggests that they may serve to slow down the translation of particular domains such that the nascent polypeptide has an opportunity to take up its conformation without interference from the later formed regions. Such a mechanism could aid localization of the protein if export were by a contranslational secretion system.

Amino Acid Sequence↗
PubMed1986

Serological properties and processing in Escherichia coli K12 of OmpV fusion proteins of Vibrio cholerae.

Fusion proteins comprising the amino-terminal 99 amino acids of the bacteriophage MS2 replicase and various portions of OmpV a major outer membrane protein of Vibrio cholerae were expressed in Escherichia coli K12. These fusions were expressed under the control of the PL promoter of bacteriophage lambda, and expression was controlled using a cIts repressor. Fusions occurring within the secretory signal sequence of OmpV gave rise to the production of mature OmpV. The efficiency, however, decreased with progressive deletion of the signal sequence within the fusions. The reactivity of various OmpV fusions with antisera raised against purified OmpV and whole bacteria demonstrated the existence of two antigenic domains: one present in the denatured form and another in the membrane-associated form of OmpV. These domains correspond to markedly hydrophilic regions of the protein as would be predicted for surface-exposed epitopes.

Amino Acid Sequence↗
PubMed1985

Role of chromosomal rearrangement in N. gonorrhoeae pilus phase variation.

N. gonorrhoeae undergoes pilus phase and antigenic variation. During phase variation, the pilin gene is turned on and off at high frequencies. Two loci on the gonococcal chromosome from strain MS11 function as expression sites for the pilin gene (pilE1 and pilE2); many other sites apparently contain silent variant pilin sequences. We reported previously that during pilus phase variation, when cells switch from the pilus expressing state (P+) to the nonexpressing state (P-), genome rearrangement occurs. We have examined phase variation in more detail, and we report that in most P+ to P- switches a deletion of pilin gene information occurs in one or both expression sites. This deletion is due to either a simple or a multiple-step recombination event involving directly repeated sequences in the expression loci. The deletion explains the state of some P- cells, but not all. In the latter cells pilin expression is probably controlled by an undefined regulator.

Bacterial Outer Membrane Proteins↗
PubMed1985

A plasmid cloning system utilizing replication and packaging functions of the filamentous bacteriophage fd.

DNA cloning vectors were developed which utilize the replication origin (ori) of bacteriophage fd for their propagation. These vectors depend on the expression of viral gene 2 that was inserted into phage lambda, which in turn was integrated into the host genome. The constitutive expression of gene 2 in the host cells is sufficient for the propagation of at least 100 pfd plasmids per cell. In addition to the fd ori, the pfd vectors carry various antibiotic-resistance genes and unique restriction sites. Some of these vectors have no homologies to commonly used pBR plasmids or to lambda DNA. The nucleotide sequence of the vectors can be deduced from published sequences. Large DNA inserts can be stably propagated in pfd vectors; these are more stable than similar DNA fragments cloned in intact genomes of filamentous bacteriophage. Inclusion of phage sequences required for efficient phage packaging and infection with a helper phage resulted in formation of phage particles containing single-stranded plasmid genomes. Growth at 42 degrees C without selective pressure results in loss of pfd plasmids.

Bacteriophage lambda↗