Dissertation/Thesis Abstract

Discovery of CZB, a novel zinc-binding domain in bacterial chemoreceptors & the genome sequence of Helicobacter pylori strain SS1
by Draper, Jenny Lyn, Ph.D., University of California, Santa Cruz, 2010, 189; 3424535
Abstract (Summary)

The pathogenic bacterium Helicobacter pylori lives in the stomach lining of more than half of the world's population, where it causes ulcers, stomach cancer, and iron deficiency. Chemotaxis, the ability to sense and move in response to a chemical environment, contributes to H. pylori's virulence. H. pylori has four chemoreceptor proteins: three classic transmembrane receptors and one atypical cytoplasmic receptor called TlpD. We previously observed that H. pylori mutants lacking TlpD are defective in their ability to infect mice.

TlpD contains an uncharacterized C-terminal domain which is fairly common in predicted cytoplasmic chemoreceptors, especially within Proteobacteria. This domain contains a highly conserved "H-C-H-H" motif, which suggested a potential metal-binding site. I purified this protein and tested its ability to bind metal ions at this motif. I discovered that it binds zinc with high affinity. The function of this domain's zinc-binding capability is still unclear. It likely plays either a functional role, as seen in other proteins containing this rare coordination motif, or a structural role, as suggested by the decreased stability of TlpD mutants lacking Zn coordination ability. We chose to name this domain "CZB" (Chemoreceptor Zinc-Binding).

In addition, I found that TlpD is both cytoplasmic and membrane-associated—an unusual distribution for cytoplasmic chemoreceptors. Likewise, TlpD appears to interact with the transmembrane chemotaxis array through the atypical chemotaxis protein CheV1, rather than the usual CheW coupling protein.

The genome of H. pylori is highly variable, resulting in many different strains with unique infectious properties. Although 9 strains have already been sequenced, none are capable of infecting mice, a common animal model for studying H. pylori's pathogenicity. We have sequenced the genome of H. pylori SS1, the most-characterized mouse-infecting strain, utilizing 454 and SOLiD paired-end technologies. However, the sequence is proving challenging to assemble, and currently exists in 51 contigs. It appears that rearrangement has occurred within subpopulations of the non-clonal SS1 sample which was sequenced. Much of this variation lies in positioning of the transposable element IS607, and rearrangements within the cytoxin-associated pathogenicity island (cag PAI), a highly variable region crucial for H. pylori's ability to cause disease.

Indexing (document details)
Advisor: Ottemann, Karen
Commitee:
School: University of California, Santa Cruz
School Location: United States -- California
Source: DAI-B 71/10, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Molecular biology, Genetics, Microbiology, Bioinformatics
Keywords: Bacterial chemoreceptors, CZB, Chemotaxis, Genome sequence, Helicobacter pylori, SS1, Zinc-binding domainin
Publication Number: 3424535
ISBN: 9781124236674
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