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bioRxiv · 10.1101/505107

Non-helical Helicobacter pylori show altered gland colonization and elicit less gastric pathology during chronic infection

Martinez, L. E.·O'Brien, V. P.·Leverich, C.·Knoblaugh, S. E.·Salama, N. R.
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Abstract

Half of all humans harbor Helicobacter pylori in their stomachs. Helical cell shape is thought to facilitate H. pyloris ability to bore into the protective mucus layer in a corkscrew-like motion, thus enhancing colonization of the stomach. H. pylori cell shape mutants show impaired colonization of the mouse stomach, highlighting the importance of cell shape in infection. To gain a deeper understanding of how helical cell morphology promotes host colonization by H. pylori, we used 3D-confocal microscopy to visualize the clinical isolate PMSS1 and an isogenic straight rod mutant ({Delta}csd6) within thick longitudinal mouse stomach sections and performed volumetric image analysis to quantify the number of bacteria residing within corpus and antral glands in addition to measuring total colony forming units (CFU). We found that straight rods show attenuation during acute colonization of the stomach (one day or one week post-infection) as measured by total CFU. Our quantitative imaging revealed that wild-type bacteria extensively colonized antral glands at one week post-infection, while csd6 mutants showed variable colonization of the antrum at this timepoint. During chronic infection (one or three months post-infection), total CFU were highly variable, but similar for wild-type and straight rods. Both wild-type and straight rods persisted and expanded in corpus glands during chronic infection. However, the straight rods showed reduced inflammation and disease progression. Thus, helical cell shape contributes to tissue interactions that promote inflammation during chronic infection, in addition to facilitating niche acquisition during acute infection.

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Martinez, L. E., O'Brien, V. P., Leverich, C., Knoblaugh, S. E., Salama, N. R.. 2018-12-26. Non-helical Helicobacter pylori show altered gland colonization and elicit less gastric pathology during chronic infection. https://doi.org/10.1101/505107

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