Biology subjects

Otsubo, R.

Publications and source records attributed to Otsubo, R..

2 recordsLinked to original sources

bioRxiv2021

CBL-C E3 ubiquitin ligase acts as a host defense to mediate ubiquitin-proteasomal degradation of enteropathogenic Escherichia coli Tir protein

Translocated intimin receptor (Tir) is an essential bacterial factor for enteropathogenic Escherichia coli (EPEC) to establish Tir-intimin interaction-mediated adherence to the epithelial cell and to form actin pedestal structures beneath the adherent bacteria. However, it remains unclear how the host cells eliminate Tir protein after infection. Here we show that intracellular translocated Tir is degraded via the host ubiquitin- proteasome system. We found that host CBL-C, an E3 ubiquitin-protein ligase, bound to and ubiquitinated the 454 tyrosine-phosphorylated Tir protein. Tir ubiquitination leads to proteasome-dependent degradation and attenuated EPEC colonization of the epithelial cell. Using Citrobacter rodentium, a mouse model for EPEC, we demonstrated that infection with C. rodentium mutant expressing a tyrosine- phenylalanine-substituted Tir (CBL-C resistant) showed increased bacterial loads in the colon and lethality compared with infection with C. rodentium expressing wild-type Tir. These results indicate that CBL-C is a critical host defense factor that determines the fate of cytosolic Tir and terminates bacterial colonization. Graphical Abstracts O_FIG O_LINKSMALLFIG WIDTH=199 HEIGHT=200 SRC="FIGDIR/small/434331v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@d28d7borg.highwire.dtl.DTLVardef@146b7e6org.highwire.dtl.DTLVardef@1d36d14org.highwire.dtl.DTLVardef@19e6b25_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2020

Helicobacter small RNA regulates host adaptation and carcinogenesis

Type-1 carcinogenic Helicobacter pylori that is known to evolve during long-term infection, enters the stomach orally and causes gastric cancer using the carcinogenic protein CagA1. However, little is known about the adaptation mechanisms of H. pylori when the environment changes from the outside to the inside of the living body. Here we show that small non-coding RNA HPnc4160 is a crucial novel RNA molecule of H. pylori that negatively regulates bacterial-host adaptation and gastric cancer. H. pylori isolated from gerbils stomachs eight weeks post-infection acquired mutations in the increased number of T-repeats within the upstream region of the HPnc4160 coding region, which leads to reduced HPnc4160 expression levels that also seen in cancer patients-derived H. pylori. By comparing RNA-seq and iTRAQ analysis between wild-type and hpnc4160 deficient mutant strains, we identified eight targets of HPnc4160 including cagA and unknown factors. Mice infection experiment revealed that the hpnc4160 deficient mutant had a higher number of colonized bacteria in the mice stomach than the wild-type strain, indicating that reduced expression levels of HPnc4160 was important for bacterial host adaptation. The expression level of HPnc4160 was lower in the clinical isolates derived from gastric cancer patients compared with non-cancer-derived strains, while the mRNA expression levels of target factors were higher. Our findings highlight the first discovery that HPnc4160 is an important small RNA for bacteria to adapt to the host environment leading to gastric carcinogenesis.

microbiology↗