Lemon exosome-like nanoparticles enhance stress survival of gut bacteria by RNase P-mediated specific tRNA decay
Chao Lei,
Yun Teng,
Liqing He,
Mohammed Sayed,
Jingyao Mu,
Fangyi Xu,
Xiangcheng Zhang,
Anil Kumar,
Kumaran Sundaram,
Mukesh K. Sriwastva,
Lifeng Zhang,
Shao-yu Chen,
Wenke Feng,
Shuangqin Zhang,
Jun Yan,
Juw Won Park,
Michael L. Merchant,
Xiang Zhang,
Huang-Ge Zhang
Affiliations
Chao Lei
James Graham Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA; Department of Medicine, University of Louisville, Louisville, KY 40202, USA
Yun Teng
James Graham Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Liqing He
Kidney Disease Program and Clinical Proteomics Center, University of Louisville, Louisville, KY, USA
Mohammed Sayed
Department of Computer Engineering and Computer Science, University of Louisville, Louisville, KY 40202, USA
Jingyao Mu
James Graham Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Fangyi Xu
James Graham Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Xiangcheng Zhang
Department of ICU, the Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu 223300, China
Anil Kumar
James Graham Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Kumaran Sundaram
James Graham Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Mukesh K. Sriwastva
James Graham Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Lifeng Zhang
James Graham Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Shao-yu Chen
Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA
Wenke Feng
Department of Medicine, University of Louisville, Louisville, KY 40202, USA
Shuangqin Zhang
Peeples Cancer Institute, 215 Memorial Drive, Dalton, GA 30720, USA
Jun Yan
James Graham Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Juw Won Park
Department of Computer Engineering and Computer Science, University of Louisville, Louisville, KY 40202, USA; KBRIN Bioinformatics Core, University of Louisville, Louisville, KY 40202, USA
Michael L. Merchant
Kidney Disease Program and Clinical Proteomics Center, University of Louisville, Louisville, KY, USA
Xiang Zhang
Kidney Disease Program and Clinical Proteomics Center, University of Louisville, Louisville, KY, USA
Huang-Ge Zhang
Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206, USA; James Graham Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA; Corresponding author
Summary: Diet and bile play critical roles in shaping gut microbiota, but the molecular mechanism underlying interplay with intestinal microbiota is unclear. Here, we showed that lemon-derived exosome-like nanoparticles (LELNs) enhance lactobacilli toleration to bile. To decipher the mechanism, we used Lactobacillus rhamnosus GG (LGG) as proof of concept to show that LELNs enhance LGG bile resistance via limiting production of Msp1 and Msp3, resulting in decrease of bile accessibility to cell membrane. Furthermore, we found that decline of Msps protein levels was regulated through specific tRNAserUCC and tRNAserUCG decay. We identified RNase P, an essential housekeeping endonuclease, being responsible for LELNs-induced tRNAserUCC and tRNAserUCG decay. We further identified galacturonic acid-enriched pectin-type polysaccharide as the active factor in LELNs to increase bile resistance and downregulate tRNAserUCC and tRNAserUCG level in the LGG. Our study demonstrates a tRNA-based gene expression regulation mechanism among lactobacilli to increase bile resistance.
