Title:

Pathogenic processes of gut commensal pathobiont

 

Speaker:

Hitoshi Tsugawa, Ph.D.

Associate Professor, Transkingdom Signaling Research Unit, Division of Host Defense Mechanism, Tokai University School of Medicine

 

Abstract:

The human gastrointestinal commensal microbiota is composed predominantly of bacteria, accounting for over 99% of its constituents, with the total number of microbial cells far exceeding that of human cells. These gut commensal bacteria play a pivotal role in modulating host metabolic responses and are considered essential for maintaining human homeostasis, earning them the designation of a “second genome.” Consequently, the human host and its microbiota together constitute a highly complex biological entity, often referred to as a “superorganism.” Among the gut microbiota are certain commensal bacteria termed pathobionts, which have attracted increasing attention due to their potential contribution to various systemic diseases. Pathobionts are defined as symbiotic organisms capable of promoting pathology only under specific genetic or environmental perturbations in the host. Their pathogenicity arises from alterations in host–microbe interactions. Understanding the gut environmental conditions that trigger the transition of pathobionts from a benign to a pathogenic state is of critical importance. In our laboratory, we investigate the mechanisms by which gut commensal bacteria acquire pathogenic potential, with a particular focus on changes in host–bacteria interactions, a process known as transkingdom signaling. In this seminar, we will discuss recent insights into transkingdom signaling dynamics that underline the transformation of symbionts into pathogenic bacteria.

 

Reference:

1. Tsugawa H, Tsubaki S, Tanaka R, Nashimoto S, Imai J, Matsuzaki J, Hozumi K. Macrophage-depleted young mice are beneficial in vivo models to assess the translocation of Klebsiella pneumonia from the gastrointestinal tract to the liver in the elderly. Microbes Infect., 105371, 2024.
2. Tsugawa H, Ohki T, Tsubaki S, Tanaka R, Matsuzaki J, Suzuki H, Hozumi K. Gas6 ameliorates intestinal mucosal immunosenescence to prevent the translocation of a gut pathobiont, Klebsiella pneumoniae, to the liver. PLoS Pathogens, 19(6): e1011139, 2023.
3. Tsugawa H, Kabe Y, Kanai A, Sugiura Y, Hida S, Taniguchi S, Takahashi T, Matsui H, Yasukawa Z, Itou H, Takubo K, Suzuki H, Honda K, Handa H, Suematsu M. Short-chain fatty acids bind to apoptosis-associated speck-like protein to activate inflammasome complex to prevent SalmonellaPLoS Biology. 18(9): e3000813, 2020.
4. Tsugawa H,Kato C, Mori H, Matsuzaki J, Kameyama K, Saya H, Hatakeyama M, Suematsu M, Suzuki H. Cancer stem-cell marker CD44v9-positive cells arise from Helicobacter pylori-infected CAPZA1-overexpressing cells.  Mol. Gastroenterol. Hepatol., 8(3): 319-334, 2019.
5. Matsuzaki J*, Tsugawa H*, Kashiwazaki Y, Mori H, Yamamoto Y, Kameyama H, Masaoka T, Kanai T, Suzuki H. Neutrophil-activating protein polymorphism of Helicobacter pyloridetermines the host risk of dyspepsia.  Mol. Gastroenterol. Hepatol., 8(2): 295-297, 2019. *Contributed equally to this work. 
6. Tsugawa H, Mori H, Matsuzaki J, Sato A, Saito Y, Imoto M, Suematsu M, Suzuki H. CAPZA1 determines the risk of gastric carcinogenesis by inhibiting Helicobcater pyloriCagA-degraded autophagy. Autophagy, 15(2): 242-258, 2019. 
7. Tsugawa H, Mori H, Matsuzaki J, Masaoka T, Hirayama T, Nagasawa H, Sakakibara Y, Suematsu M, Suzuki H. Nordihydroguaiaretic Acid disrupts the antioxidant ability of Helicobacter pylori through the repression of SodB activity in vitro.  Res. Int., 734548, 2015.
8. Tsugawa H, Suzuki H, Saya H, Hatakeyama M, Hirayama T, Hirata K, Nagano O, Matsuzaki J, Hibi T. Reactive oxygen species-induced autophagic degradation of Helicobacter pyloriCagA is specifically suppressed in cancer stem-like cells. Cell Host Microbe, 12(6):764-777, 2012.