No abstract

Helicobacter pylori persistently colonizes the harsh and dynamic environment of the stomach in over one-half of the world's population and has been identified as a causal agent in a spectrum of pathologies that range from gastritis to invasive adenocarcinoma. The ferric uptake regulator (Fur) is one of the few regulatory proteins that has been identified in H. pylori. Fur regulates genes important for acid acclimation and oxidative stress and has been shown to be important for colonization of H. pylori in both murine and Mongolian gerbil models of infection. To more thoroughly define the role of Fur in vivo, we conducted an extensive temporal analysis of the location of, competitive ability of, and resultant pathology induced by a ⌬fur strain in the Mongolian gerbil model of infection and compared the results to results for its wild-type parent. We found that at the earliest time points postinfection, significantly more ⌬fur bacteria than wild-type bacteria were recovered. However, this trend was reversed by day 3, when there was significantly increased recovery of the wild-type strain. The increased recovery of the ⌬fur strain at 1 day postinfection reflected increased recovery from both the corpus and the antrum of the stomach. When the wild-type strain was allowed to colonize first, the ⌬fur strain was unable to compete for colonization at any time postinfection. However, when the ⌬fur strain was allowed to colonize first, the wild type efficiently outcompeted the ⌬fur strain only at early times postinfection. Finally, we demonstrated that there was a delay in the development and severity of inflammation and pathology of the ⌬fur strain in the gastric mucosa even after comparable levels of colonization occurred. Together, these data indicate that H. pylori Fur is most important at early stages of infection and illustrate the importance of the ability of H. pylori to adapt to its constantly fluctuating environment when it is establishing infection, inflammation, and disease.

We characterized the MHC class II B gene in the green-rumped parrotlet, Forpus passerinus. Three approaches were used: polymerase chain reaction amplification using primers complementary to conserved regions of exon 2, sequencing clones from a genomic library, and amplification of exon 2 using species-specific primers. All three methods indicate that there is only a single class II B locus in this species and no pseudogenes. We suggest that this is the ancestral state for birds. The gene is highly polymorphic; 33 alleles were found in a sample of 25 individuals. Variation in exon 2 is concentrated in the peptide binding residues which show a significant excess of non-synonymous substitutions consistent with the operation of selection in maintaining this extraordinary polymorphism. Genomic clones show that major histocompatibility complex (MHC) gene organization is different from that of chickens; the class II A locus is close to II B. These data provide support for the hypothesis that the bird MHC constitutes a "minimal essential MHC" for responding to infectious disease.

The Ferric Uptake Regulator (Fur) is a transcriptional regulator that is conserved across a broad number of bacterial species and has been shown to regulate expression of iron uptake and storage genes. Additionally, Fur has been shown to be an important colonization factor of the gastric pathogen Helicobacter pylori. In H. pylori, Fur-dependent regulation appears to be unique in that Fur is able to act as a transcriptional repressor when bound to iron as well as in its iron free (apo) form. To date, apo-regulation has not been identified in any other bacterium. To determine whether Fur from other species has the capacity for apo-regulation, we investigated the ability of Fur from Escherichia coli, Campylobacter jejuni, Desulfovibrio vulgaris Hildenborough, Pseudomonas aeruginosa, and Vibrio cholerae to complement both iron-bound and apo-Fur regulation within the context of an H. pylori fur mutant. We found that while some Fur species (E. coli, C. jejuni and V. cholerae) complemented iron-bound regulation, apo-regulation was unable to be complemented by any of the examined species. These data suggest that despite the conservation among bacterial Fur proteins, H. pylori Fur contains unique structure/function features that make it novel in comparison to Fur from other species.