Multiple Acid Sensors Control Helicobacter pylori Colonization of the Stomach

PLoS Pathogens

Julie Y. Huang¹  Manuel R. Amieva²  Emily Goers Sweeney³  Karen Guillemin³ 

[1] Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America;Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada;Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America

关键词: Helicobacter pylori;    Stomach;    Urea;    Swimming;    Bacteria;    Hydrochloric acid;    Pathogen motility;    Ureases;   

DOI  :  10.1371/journal.ppat.1006118

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Helicobacter pylori’s ability to respond to environmental cues in the stomach is integral to its survival. By directly visualizing H. pylori swimming behavior when encountering a microscopic gradient consisting of the repellent acid and attractant urea, we found that H. pylori is able to simultaneously detect both signals, and its response depends on the magnitudes of the individual signals. By testing for the bacteria’s response to a pure acid gradient, we discovered that the chemoreceptors TlpA and TlpD are each independent acid sensors. They enable H. pylori to respond to and escape from increases in hydrogen ion concentration near 100 nanomolar. TlpD also mediates attraction to basic pH, a response dampened by another chemoreceptor TlpB. H. pylori mutants lacking both TlpA and TlpD (ΔtlpAD) are unable to sense acid and are defective in establishing colonization in the murine stomach. However, blocking acid production in the stomach with omeprazole rescues ΔtlpAD’s colonization defect. We used 3D confocal microscopy to determine how acid blockade affects the distribution of H. pylori in the stomach. We found that stomach acid controls not only the overall bacterial density, but also the microscopic distribution of bacteria that colonize the epithelium deep in the gastric glands. In omeprazole treated animals, bacterial abundance is increased in the antral glands, and gland colonization range is extended to the corpus. Our findings indicate that H. pylori has evolved at least two independent receptors capable of detecting acid gradients, allowing not only survival in the stomach, but also controlling the interaction of the bacteria with the epithelium.

【 授权许可】

CC BY