Multiple Acid Sensors Control Helicobacter pylori Colonization

of the Stomach

Julie Y. Huang, et al. PLoS Pathogens 13(1): e1006118. (2017)

Speaker: Yi Tien (田 依)                                              Time: 13:00~14:00, Mar. 01, 2017

Commentator: Dr. Pei-Jane Tsai (蔡佩珍老師)           Place: Room 601

Abstract

Helicobacter pylori (H. pylori) is one of the most successful human pathogens, which colonizes the mucus layer of the gastric epithelium of more than 50% of the world’s population. Although the fact that H. pylori persist in the stomach, it is not an acidophile and has developed strategies to avoid the acidic environment using motility and chemotaxis. The cues H. pylori senses to locate and colonize the gastric epithelium have not been well defined. Previous studies have reported that the TlpB, a chemoreceptor, is responsible for sensing HCl as a repellent and showed high affinity that allows H. pylori to sensitively detect and swim towards urea which is emanating from the gastric epithelium [1]. Therefore, the author further investigate how H. pylori sense both a repellent and an attractant through TlpB. First, the author used a microscopic gradient with the point source at the micropipette tip and monitored the bacterial chemotactic responses to the gradient in real time using phase-contrast video microscopy [2]. Accidentally, they found that ΔtlpB mutants are not defective in detecting and swimming away from HCl gradients. Using other H. pylori mutants, TlpA and TlpD were identified as independent acid sensors with different sensitivities to HCl. In order to explore the impact of colonization by lacking acid sensor strains, the author created a H. pylori-infected murine model. The double mutant lacking TlpA and TlpD (ΔtlpAD) is defective in its ability to colonize the stomach compared to wild-type H. pylori. Treatment with omeprazole, a proton-pump inhibitor whose raises the gastric pH and restores the ΔtlpAD mutant's defect, allowing it to reach significantly higher bacterial numbers in the murine stomach. Altogether, these results revealed that TlpA and TlpD are important in establishing colonization deep in the gastric glands. This study identified two dominant acid sensors to control H. pylori’s localization and survival in the harshest gastric environments.

References:

1.         Goers Sweeney E,  Henderson JN, et al. Structure 3; 20(7):1177-88. (2012) Structure and proposed mechanism for the pH-sensing Helicobacter pylori chemoreceptor TlpB.

1.              Huang JY,  Sweeney EG, et al. Cell  Host  Microbe 12; 18(2):147-56. (2015) Chemodetection and  Destruction  of  Host  Urea  Allows  Helicobacter  pylori  to  Locate  the  Epithelium.

2.