Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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A meningococcal genomic expression library was screened for potent CD4+ T-cell antigens, using patients' peripheral blood lymphocytes (PBLs). One of the most promising positive clones was fully characterized. The recombinant meningococcal DNA contained a single, incomplete, open reading frame (ORF), which was fully reconstructed with reference to available genomic sequence data. The gene was designated autA (auto-transporter A) as its peptide sequence shares molecular characteristics of the auto-transporter family of proteins. Only a single copy of this gene was detected in the meningococcal, and none in the gonococcal, genomic sequence databases. The complete autA gene, when cloned into an expression vector, expressed a protein of approximately 68 kDa. Purified rAutA recalled strong secondary T-cell responses in PBLs of patients and some healthy donors, and induced strong primary T-cell responses in healthy donors. The human B-cell immunogenicity and cross-reactivity of AutA, purified under native conditions, was confirmed in dot immunoblot experiments. Immunoblots with rabbit polyclonal antibodies to rAutA demonstrated the conserved nature, antigenicity and cross-reactivity of AutA amongst meningococci of different serogroups and strains representing different hypervirulent lineages. AutA showed homology with another meningococcal and gonococcal ORF (designated AutB). AutB was cloned and expressed and used to raise an autB-specific antiserum. Immunoblot experiments indicated that AutB is not expressed in meningococci and does not cross-react with AutA. Thus, AutA, being a potent CD4+ T-cell and B-cell-stimulating antigen, which is highly conserved, deserves further investigation as a potential vaccine candidate.
Mol Microbiol 2000 Sep
PMID:Auto-transporter A protein of Neisseria meningitidis: a potent CD4+ T-cell and B-cell stimulating antigen detected by expression cloning. 1097 28

Neisseria gonorrhoeae lacks several common DNA repair pathways found in other organisms. As recent evidence had indicated that gonococci use recombinational repair to repair UV-induced DNA lesions, this study examined whether the gonococcal RecJ homologue contributes in this repair capacity. The recJ gene from strain MS11 was cloned and sequenced and was found to show a considerable degree of identity to its Escherichia coli homologue. A N. gonorrhoeae delta recJ mutant was constructed and tested for recombinational proficiency as well as for defects in DNA repair. In the absence of the RecJ exonuclease, DNA transformation and pilin switching occurred at wild type levels, indicating that the efficiency of recombination remained unimpaired. In contrast, N. gonorrhoeae delta recJ mutants showed extreme sensitivity to low levels of UV irradiation and to exposure to DNA-alkylating reagents [e.g. ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS)]. Complementation of the gonococcal recJ mutant in cis restored resistance to low-level UV, indicating that the gonococcal RecJ protein is involved in recombinational repair, and can act independently of other single-strand-specific exonucleases. Furthermore, transformation competence was not required for RecJ-dependent DNA repair. Overall, the data show that N. gonorrhoeae recJ mutants present a unique phenotype when compared to their E. coli recJ counterparts, and further support the contention that RecORJ-dependent recombinational repair is a major DNA repair pathway in the genus Neisseria.
Mol Gen Genet 2000 Oct
PMID:Neisseria gonorrhoeae recJ mutants show defects in recombinational repair of alkylated bases and UV-induced pyrimidine dimers. 1108 66

Neisseria gonorrhoeae (the gonococcus) is the causative agent of the sexually transmitted disease gonorrhoea. Most gonococcal infections remain localized to the genital tract but, in a small proportion of untreated cases, the bacterium becomes systemic to produce the serious complication of disseminated gonococcal infection (DGI). We have identified a large region of chromosomal DNA in N. gonorrhoeae that is not found in a subset of gonococcal isolates (a genetic island), in the closely related pathogen, Neisseria meningitidis or in commensal Neisseria that do not usually cause disease. Certain versions of the island carry a serum resistance locus and a gene for the production of a cytotoxin; these versions of the island are found preferentially in DGI isolates. All versions of the genetic island encode homologues of F factor conjugation proteins, suggesting that, like some other pathogenicity islands, this region encodes a conjugation-like secretion system. Consistent with this hypothesis, a wild-type strain released large amounts of DNA into the medium during exponential growth without cell lysis, whereas an isogenic strain mutated in a peptidoglycan hydrolase gene (atlA) was drastically reduced in its ability to donate DNA for transformation during growth. This genetic island constitutes the first major discriminating factor between the gonococcus and the other Neisseria and carries genes for providing DNA for genetic transformation.
Mol Microbiol 2001 Jul
PMID:A variable genetic island specific for Neisseria gonorrhoeae is involved in providing DNA for natural transformation and is found more often in disseminated infection isolates. 1145 18

LPS is a fundamental constituent of the outer membrane of all Gram-negative bacteria, and the lipid A domain plays a central role in the induction of inflammatory responses. We identified genes of the Neisseria gonorrhoeae lipid A biosynthetic pathway by searching the complete gonococcal genome sequence with sequences of known enzymes from other species. The lpxLII gene was disrupted by an insertion-deletion in an attenuated aroA mutant of the gonococcal strain MS11. Lipopolysaccharide (LPS) and lipid A analysis demonstrated that the lpxLII mutant had synthesized an altered LPS molecule lacking a single lauric fatty acid residue in the GlcN II of the lipid A backbone. LPS of the lpxLII mutant had a markedly reduced ability to induce the proinflammatory cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-8 from human macrophages and IL-8 from polymorphonuclear cells. This study demonstrates that the lpxLII gene in gonococci encodes for a late-functioning lauroyl acyl transferase that adds a lauric acid at position 2' in the lipid A backbone. The presence of lauric acid at such a position appears to be crucial for the induction of full inflammatory responses by N. gonorrhoeae LPS.
Mol Microbiol 2001 Oct
PMID:The Neisseria gonorrhoeae lpxLII gene encodes for a late-functioning lauroyl acyl transferase, and a null mutation within the gene has a significant effect on the induction of acute inflammatory responses. 1167 76

Urethral epithelial cells are invaded by Neisseria gonorrhoeae during gonococcal infection in men. To understand further the mechanisms of gonococcal entry into host cells, we used the primary human urethral epithelial cells (PHUECs) tissue culture system recently developed by our laboratory. These studies showed that human asialoglycoprotein receptor (ASGP-R) and the terminal lactosamine of lacto-N-neotetraose-expressing gonococcal lipooligosaccharide (LOS) play an important role in invasion of PHUECs. Microscopy studies showed that ASGP-R traffics to the cell surface after gonococcal challenge. Co-localization of ASGP-R with gonococci was observed. As ASGP-R-mediated endocytosis is clathrin dependent, clathrin localization in PHUECs was examined after infection. Infected PHUECs showed increased clathrin recruitment and co-localization of clathrin and gonococci. Preincubating PHUECs in 0.3 M sucrose or monodansylcadaverine (MDC), which both inhibit clathrin-coated pit formation, resulted in decreased invasion. N. gonorrhoeae strain 1291 produces a single LOS glycoform that terminates with Gal(beta1-4)GlcNac(beta1-3)Gal(beta1-4)Glc (lacto-N-neotetraose). Invasion assays showed that strain 1291 invades significantly more than four isogenic mutants expressing truncated LOS. Sialylation of strain 1291 LOS inhibited invasion significantly. Preincubation of PHUECs in asialofetuin (ASF), an ASGP-R ligand, significantly reduced invasion. A dose-response reduction in invasion was observed in PHUECs preincubated with increasing concentrations of NaOH-deacylated 1291 LOS. These studies indicated that an interaction between lacto-N-neotetraose-terminal LOS and ASGP-R allows gonococcal entry into PHUECs.
Mol Microbiol 2001 Nov
PMID:Receptor-mediated endocytosis of Neisseria gonorrhoeae into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor. 1172 33

We tested the susceptibility patterns of 128 N. gonorrhoeae isolates to six antimicrobials; penicillin, tetracycline, spectinomycin, ceftriaxone, ciprofloxacin and azithromycin, and examined whether certain demographic or behavioral factors related to antibiotic use increased the likelihood of infection by a resistant strain. There was a low rate of resistance to penicillin; penicillinase-producing and chromosomal-mediated penicillin resistant gonorrhea were estimated to be 0.8%. A much higher proportion of isolates were resistant to tetracycline (up to 15%). All isolates were sensitive to spectinomycin, ciprofloxacin and ceftriaxone. However, less than 2% of isolates displayed intermediate resistance to both ciprofloxacin and ceftriaxone, and 9% exhibited intermediate resistance to spectinomycin. Patients who had obtained medication before attending the clinic and had taken all of the medication were more likely (p = 0.03) to be infected with a resistant strain of gonococcus. Also, patients who were asked by a clinic doctor to return for a test of cure during an earlier clinic visit, but who did not return were more likely to be infected with a resistant organism (p = 0.006) compared to those who returned at the doctor's request. These findings have important implications for antibiotic use and educational programs in Trinidad and Tobago.
Cell Mol Biol (Noisy-le-grand) 2001 Sep
PMID:Antibiotic resistant N. gonorrhoeae in Trinidad and Tobago. 1178 65

Genetic linkage within Neisseria gonorrhoeae populations is in equilibrium, yet the physical linkage map indicates a relatively stable chromosome structure, despite an apparently vast potential for mispairing between repeated sequences (e.g. between the multiple pil or opa alleles, or through mispairing of any of the numerous small repeated sequences that are liberally scattered throughout the chromosome). Therefore, the stability of the physical linkage map suggests that aberrant recombination between repeated sequences is a rare event. This study was undertaken to explore some of the parameters that may govern deletion events between short direct oligonucleotide repeats, using a chromosomal locus that appears to be especially prone to deletions (the pilin expression locus; pilE). In this report, we demonstrate that deletion formation at pilE occurs primarily through recombinational error following a pilE/pilS interaction; illegitimate (i.e. RecA-independent) events can occur, but they are infrequent. In contrast, when genetically engineered opa deletion substrates were constructed and placed in the chromosome, deletions at the opa loci were infrequent even under rec(+) conditions. A model is presented in which the gonococcal RecA and RecJ proteins promote pilE deletions through a recombination event that is templated or stabilised by a pilE/pilS interaction.
Mol Genet Genomics 2002 Feb
PMID:Recombinational error and deletion formation in Neisseria gonorrhoeae: a role for RecJ in the production of pilE (L) deletions. 1186 90

Diagnosis of chlamydial and gonococcal infections is the foundation of most sexually transmitted infection control programs. Early detection and treatment of disease is essential for disruption of transmission. DNA-based assays have been shown to have the highest available sensitivity and specificity but are often time-consuming and technically demanding. The COBAS Amplicor is an automated system that performs a combined chlamydia and gonorrhea diagnostic assay suitable for use in either public health or reference laboratories.
Expert Rev Mol Diagn 2002 Jul
PMID:COBAS Amplicor: an automated PCR system for detection of C. trachomatis and N. gonorrhoeae. 1213 3

Min proteins are involved in the correct placement of division septa in many bacterial species. In Escherichia coli (Ec) cells, these proteins oscillate from pole to pole, ostensibly to prevent unwanted polar septation. Here, we show that Min proteins from the coccus Neisseria gonorrhoeae (Ng) also oscillate in E. coli. Green fluorescent protein (GFP) fusions to gonococcal MinD and MinE localized dynamically in different E. coli backgrounds. GFP-MinDNg moved from pole to pole in rod-shaped E. coli cells with a 70 +/- 25 s localization cycle when MinENg was expressed in cis. The oscillation time of GFP-MinDNg was reduced when wild-type MinENg was replaced with MinENg carrying a R30D mutation, but lengthened by 15 s when activated by MinEEc. Several mutations in the N-terminal domain of MinDNg, including K16Q and 4- and 19-amino acid truncations, prevented oscillation; these MinDNg mutants showed decreased or lost interaction with themselves and MinENg. Like MinEEc-GFP, MinENg-GFP formed MinE rings and oscillated in E. coli cells when MinDEc was expressed in cis. Finally, in round E. coli cells, GFP-MinDNg appeared to move in a plane parallel to completed septa. This pattern of movement is predicted to be similar in gonococcal cells, which also divide in alternating perpendicular planes.
Mol Microbiol 2002 Oct
PMID:Conservation of dynamic localization among MinD and MinE orthologues: oscillation of Neisseria gonorrhoeae proteins in Escherichia coli. 1240 24

Although natural genetic transformation is a widely disseminated form of genetic exchange in prokaryotic species, the proficiencies with which DNA recognition, uptake and processing occur in nature vary greatly. However, the molecular factors and interactions underlying intra- and interspecies diversity in levels of competence for natural genetic transformation are poorly understood. In Neisseria gonorrhoeae, the Gram-negative aetiologic agent of gonorrhoea, DNA binding and uptake involve components required for Type IV pilus (Tfp) biogenesis as well as those which are structurally related to Tfp biogenesis components but dispensable for organelle expression. We demonstrate here that the gonococcal PilV protein, structurally related to Tfp pilin subunits, is an intrinsic inhibitor of natural genetic transformation which acts ultimately by reducing the levels of sequence-specific DNA uptake into the cell. Specifically, we show that DNA uptake is enhanced in strains bearing pilV mutations and reduced in strains overexpressing PilV. Furthermore, we show that PilV exerts its effect by acting as an antagonist of ComP, a positive effector of sequence-specific DNA binding. As it prevents the accumulation of ComP at a site where it can be purified by shear extraction of intact cells, the data are most consistent with PilV either obstructing ComP trafficking or altering ComP stability. In addition, we report that ComP and PilV play overlapping and partially redundant roles in Tfp biogenesis and document other genetic interactions between comP and pilV together with the pilE and pilT genes required for the expression of retractile Tfp. Together, the results reveal a novel mechanism by which the levels of competence are governed in prokaryotic species and suggest unique ways by which competence might be modulated.
Mol Microbiol 2002 Dec
PMID:An inhibitor of DNA binding and uptake events dictates the proficiency of genetic transformation in Neisseria gonorrhoeae: mechanism of action and links to Type IV pilus expression. 1245 28


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