Identification and characterisation of a novel adhesin Ifp in Yersinia pseudotuberculosis.

Background: In order to identify new virulence determinants in Y. pseudotuberculosis a comparison between its genome and that of Yersinia pestis was undertaken. This reveals dozens of pseudogenes in Y.

YtxR acts as an overriding transcriptional off switch for the Yersinia enterocolitica Ysc-Yop type 3 secretion system.

The Yersinia enterocolitica YtxR protein is a LysR-type transcriptional regulator that induces expression of the ytxAB locus, which encodes a putative ADP-ribosylating toxin. The ytxR and ytxAB genes are not closely linked in the Y. enterocolitica chromosome, and whereas ytxR is present in all sequenced Yersinia spp.

The Yersinia pseudotuberculosis and Yersinia pestis toxin complex is active against cultured mammalian cells.

The toxin complex (Tc) genes were first identified in the insect pathogen Photorhabdus luminescens and encode approximately 1 MDa protein complexes which are toxic to insect pests. Subsequent genome sequencing projects have revealed the presence of tc orthologues in a range of bacterial pathogens known to be associated with insects. Interestingly, members of the mammalian-pathogenic yersiniae have also been shown to encode Tc orthologues.

The importance of the Rcs phosphorelay in the survival and pathogenesis of the enteropathogenic yersiniae.

The human-pathogenic yersiniae represent an ideal species group to study the evolution of highly virulent bacteria, with Yersinia pestis having emerged from the enteropathogen Y. pseudotuberculosis an estimated 20 000 years ago. Sequence data reveal that the Y.

The insect toxin complex of Yersinia.

Many members of the Yersinia genus encode homologues of insect toxins first observed in bacteria that are insect pathogens such as Photorhabdus, Xenorhabdus and Serratia entomophila. These bacteria secrete high molecular weight insecticidal toxins comprised of multiple protein subunits, termed the Toxin Complexes or Tc's. In Photorhabdus three distinct Tc subunits are required for full oral toxicity in insects, that include the [A], [B] and [C] types, although the exact stochiometry remains unclear.

The RovA regulons of Yersinia enterocolitica and Yersinia pestis are distinct: evidence that many RovA-regulated genes were acquired more recently than the core genome.

RovA is a transcriptional activator of Yersinia invasin, an outer membrane protein involved in bacterial attachment and invasion across the intestinal epithelium. In Y. enterocolitica, a rovA mutant is attenuated for virulence compared with either wild-type or inv mutant strains, indicating that RovA may regulate additional virulence factors.

Comparative phylogenomics of pathogenic bacteria by microarray analysis.

DNA microarrays represent a powerful technology that enables whole-scale comparison of bacterial genomes. This, coupled with new methods to model DNA microarray data, is facilitating the development of robust comparative phylogenomics analyses. Such studies have dramatically increased our ability to differentiate between bacteria, highlighting previously undetected genetic differences and population structures and providing new insight into virulence and evolution of bacterial pathogens.

Analysis of varicella zoster virus attenuation by evaluation of chimeric parent Oka/vaccine Oka recombinant viruses in skin xenografts in the SCIDhu mouse model.

Varicella-zoster virus (VZV) is the only human herpes virus for which a vaccine has been licensed. A clinical VZV isolate, designated the parent Oka (pOka) strain was passed in human and non-human fibroblasts to produce vaccine Oka (vOka). The pOka and vOka viruses exhibit similar infectivity in cultured cells but healthy susceptible individuals given vaccines derived from vOka rarely develop the cutaneous vesicular lesions characteristic of varicella.

Application of DNA microarrays to study the evolutionary genomics of Yersinia pestis and Yersinia pseudotuberculosis.

Yersinia pestis, the causative agent of plague, diverged from Yersinia pseudotuberculosis, an enteric pathogen, an estimated 1500-20,000 years ago. Genetic characterization of these closely related organisms represents a useful model to study the rapid emergence of bacterial pathogens that threaten mankind. To this end, we undertook genome-wide DNA microarray analysis of 22 strains of Y.

Construction of varicella-zoster virus recombinants from parent Oka cosmids and demonstration that ORF65 protein is dispensable for infection of human skin and T cells in the SCID-hu mouse model.

We generated an ORF65 deletion mutant by using a cosmid system constructed from the genome of a low-passage clinical isolate (P-Oka). Using the SCID-hu mouse model, we demonstrated that the ORF65 protein is dispensable for viral replication in skin and T cells, which are critical host cell targets during primary varicella-zoster virus infection.

Mutational analysis of open reading frames 62 and 71, encoding the varicella-zoster virus immediate-early transactivating protein, IE62, and effects on replication in vitro and in skin xenografts in the SCID-hu mouse in vivo.

The varicella-zoster virus (VZV) genome has unique long (U(L)) and unique short (U(S)) segments which are flanked by internal repeat (IR) and terminal repeat (TR) sequences. The immediate-early 62 (IE62) protein, encoded by open reading frame 62 (ORF62) and ORF71 in these repeats, is the major VZV transactivating protein. Mutational analyses were done with VZV cosmids generated from parent Oka (pOka), a low-passage clinical isolate, and repair experiments were done with ORF62 from pOka and vaccine Oka (vOka), which is derived from pOka.

Coxsackie B viruses that use human DAF as a receptor infect pig cells via pig CAR and do not use pig DAF.

Coxsackie B viruses (CVB) are enteroviruses belonging to the family Picornaviridae. Serotypes 1, 3 and 5 of CVB bind to the human membrane complement regulator decay-accelerating factor (DAF) and the coxsackievirus/adenovirus receptor (CAR), using either or both as receptors. These viruses are known to infect pig cell lines, but the receptor(s) involved has not been identified.