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Abstract

<p>Helicobacter pylori is a Gram negative bacterial pathogen that infects the stomachs of half of all people. While most H. pylori infections result in asymptomatic gastritis, about 10% result in gastric and duodenal ulcers and 1-2% result in non-cardia stomach cancer. H. pylori is the only bacterium that is classified by the World Health Organization as a carcinogen.</p>

<p>H. pylori’s helical shape is important for stomach colonization; in a mouse model of infection, straight-rod mutants of H. pylori are ten times less efficient at colonization than their wild-type helical counterparts. Several proteins have been found that are essential for maintaining helical cell shape. Many of these proteins are enzymes that directly modify cell wall structure. The non-enzymatic cell shape determining proteins may help localize these enzymes. One of these is CcmA, a putative cytoskeletal protein, which I hypothesize to localize preferentially to areas with particular cell surface curvatures to help pattern helical shape in wild-type cells. To study this, I use an advanced 3D cell modelling algorithm to measure the precise shape of the cells and the localization of CcmA. CcmA shows enrichment along the major helical axis, which corresponds to Gaussian curvatures between 0 and 10 ?m-2. In addition to studying CcmA localization in wild-type cells, I have studied it in ?csd2 and ?csd6 mutants, which have a curved- and straight-rod shape respectively. In the mutant cells, I found the surprising result that CcmA is more enriched at regions with negative Gaussian curvature. This implies that Csd2/6 functionality are essential to CcmA’s proper localization. In addition to showing the mislocalization of CcmA, I helped improve the throughput of this cell shape modeling method and data analytics package. The localization of these cell shape proteins furthers our understanding of the basic science of cell shape determination and may be useful in the development of novel therapeutics that target cell shape to fight against this insidious pathogen.</p>

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