Biomedical subjects

Vega Masignani

Publications and source records attributed to Vega Masignani.

22 records · Page 2Linked to original sources

PubMed2002

Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae.

The 2,160,267 bp genome sequence of Streptococcus agalactiae, the leading cause of bacterial sepsis, pneumonia, and meningitis in neonates in the U.S. and Europe, is predicted to encode 2,175 genes. Genome comparisons among S. agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, and the other completely sequenced genomes identified genes specific to the streptococci and to S. agalactiae. These in silico analyses, combined with comparative genome hybridization experiments between the sequenced serotype V strain 2603 V/R and 19 S. agalactiae strains from several serotypes using whole-genome microarrays, revealed the genetic heterogeneity among S. agalactiae strains, even of the same serotype, and provided insights into the evolution of virulence mechanisms.

Amino Acid Sequence↗

PubMed2002

NadA, a novel vaccine candidate of Neisseria meningitidis.

Neisseria meningitidis is a human pathogen, which, in spite of antibiotic therapy, is still a major cause of mortality due to sepsis and meningitis. Here we describe NadA, a novel surface antigen of N. meningitidis that is present in 52 out of 53 strains of hypervirulent lineages electrophoretic types (ET) ET37, ET5, and cluster A4. The gene is absent in the hypervirulent lineage III, in N. gonorrhoeae and in the commensal species N. lactamica and N. cinerea. The guanine/cytosine content, lower than the chromosome, suggests acquisition by horizontal gene transfer and subsequent limited evolution to generate three well-conserved alleles. NadA has a predicted molecular structure strikingly similar to a novel class of adhesins (YadA and UspA2), forms high molecular weight oligomers, and binds to epithelial cells in vitro supporting the hypothesis that NadA is important for host cell interaction. NadA induces strong bactericidal antibodies and is protective in the infant rat model suggesting that this protein may represent a novel antigen for a vaccine able to control meningococcal disease caused by three hypervirulent lineages.

Alleles↗

PubMed2002

Reverse vaccinology: a genome-based approach for vaccine development.

During the last century several approaches have been followed for the development of vaccines. These include live-attenuated viruses and bacteria, killed microorganisms and the subunit vaccines [1]. With the introduction of recombinant DNA technologies, new approaches have been exploited for vaccine manufacturing. However, the major problem remains the rapid identification of highly immunogenic and protective antigens suitable for vaccine development, which still relies on standard biochemical and microbiological techniques. The advent of genomics has greatly contributed to providing a new impulse to the microbial field. The complete genomic sequence of a human pathogen represents a new unexploited field, to be used for the design of novel vaccines and antimicrobial drugs. In the case of meningococcus B, four decades of continuous efforts, using conventional technologies of purifying antigens from the microorganism, had not been sufficient to deliver an effective and universal vaccine. It was therefore decided to obtain the genomic sequence of serogroup B Neisseria meningitidis (MenB) and use this information to identify vaccine candidates. This approach was named "reverse vaccinology"[2].

Animals↗

PubMedDate not supplied

Vir90, a virulence-activated gene coding for a Bordetella pertussis iron-regulated outer membrane protein.

Bordetella pertussis undergoes phenotypic changes modulated by the bvgAS locus, which regulates the expression of many genes related to virulence and immunogenicity. We previously reported the N-terminal sequence of a 90 kDa bvg-regulated outer membrane protein (OMP) of B. pertussis (SWISS-PROT accession No. p81549), a novel potential virulence factor that we named Vir90. The open reading frames (ORFs) which potentially code for Vir90 in B. pertussis, B. parapertussis and B. bronchiseptica were identified by computer analysis of the genomic sequences available for the three Bordetella species. Nucleotide sequence analysis of the vir90 upstream region revealed the presence of a putative promoter, a BvgA binding site and a putative Fur binding site. The B. pertussis Vir90 protein showed significant homology with ferrisiderophore receptors from Gram-negative bacteria. An antiserum raised against Vir90His recombinant protein recognized the 90-kDa protein in immunoblots of OMPs from these three virulent Bordetella species. The accumulation of the Vir90 protein increased 4-fold under low iron growth conditions. Therefore, the vir90 gene is expressed in the tested species and its expression is regulated positively by the BvgAS system and negatively under high iron concentration, likely by Fur.

Amino Acid Sequence↗