Publications

2026

2025

Molecular basis of the hepatobiliary tropism of typhoid toxin promoting Salmonella pathogenicity

HY Kim, GY Lee, AJ Thompson, R McBride, D-J Fu, JC Paulson, and J Song

Science Advances 11:eadt2040 (2025)

doi.org/10.1126/sciadv.adt2040

S. Typhi produces two forms of typhoid toxin using distinct receptor-binding subunits, PltB and PltC. Unlike PltB toxin, the tropism and functional consequences of PltC toxin had not been elucidated. This study demonstrates that PltC toxin targets the hepatobiliary system by binding sulfated glycans, reducing bile acid levels, and promoting S. Typhi colonization in mice. These findings reveal a unique exotoxin mechanism that enhances S. Typhi pathogenicity by targeting the hepatobiliary system.

Rifampin mediated decapsulation and enhanced bacterial clearance: a new mechanism of rifamycins

GY Lee, and J Song

eBioMedicine 117:105787 (2025)

doi.org/10.1016/j.ebiom.2025.105787

The bacterial capsule protects pathogens from host immune defenses and antimicrobials. This study introduces a novel concept, “decapsulation”, which eliminates the Vi capsule from S. Typhi and S. Paratyphi C, thereby rendering them vulnerable to the host immune system. Genomic analyses of other key encapsulated pathogens suggest that decapsulation has the potential to be applied broadly. These results highlight a promising strategy for developing therapies against encapsulated pathogens.

2024

Single missense mutations in Vi capsule synthesis genes confer hypervirulence to Salmonella Typhi

GY Lee, and J Song

Nature Communications 15(1) (2024)

doi.org/10.1038/s41467-024-49590-6

Given the role of S. Typhi Vi capsule in pathogenesis and its use as a major component of the typhoid vaccine, the emergence of Vi variants may be inevitable. This paper reveals S. Typhi continuously evolves to diversify its Vi capsule; 20% of circulating S. Typhi strains are Vi capsule variants. Notably, hyper Vi capsule strains are hypervirulent and globally disseminated, raising concerns about their heightened virulence and their potential resistance to current prevention and treatment methods.

2023

The SARS-CoV-2 accessory protein Orf3a is not an ion channel, but does interact with trafficking proteins

AN Miller, PR Houlihan, E Matamala, D Cabezas-Bratesco, GY Lee, B Cristofori-Armstrong, TL Dilan, S Sanchez-Martinez, D Matthies, R Yan, Z Yu, D Ren, SE Brauchi, DE Clapham

eLife 12:e84477 (2023)

doi.org/10.7554/eLife.84477

Misconceptions about scientific results hinder our efforts to treat diseases. SARS-CoV Orf3a had long been considered an ion channel, but this collaborative work reveals that it does not function as an ion channel. Instead, Orf3a interacts with host cell trafficking proteins, potentially altering intracellular transport processes during infection. This paper clarifies the structural and functional properties of ORF3a, guiding the field away from misplaced therapeutic targets.

2022

2021

2020

Romo1-Derived Antimicrobial Peptide Is a New Antimicrobial Agent against Multidrug-Resistant Bacteria in a Murine Model of Sepsis

H Lee, D You, HK Kim, JW Sohn, MJ Kim, JK Park, GY Lee#, and YD Yoo#

mBio 11(2) (2020)

#, co-corresponding authors

doi.org/10.1128/mbio.03258-19

Pore-forming antimicrobial peptides (AMPs) show promise against antimicrobial resistance but are often limited by in vivo inactivation and toxicities. AMP derived from the pore-forming domain of mitochondrial channel Romo1 (AMPR) exhibits broad-spectrum efficacy against multidrug-resistant Gram-negative and Gram-positive pathogens without adverse effects in a murine sepsis model. This breakthrough makes it the first pore-forming AMP to achieve in vivo effectiveness without serious side effects and has led to its development as the lead peptide for clinical translation. Non-clinical trials are underway at ANDANTE FM CO., LTD., a startup funded by Korea’s Tech Incubator Program for Startups.

2019

2018

Romo1 is a mitochondrial nonselective cation channel with viroporin-like characteristics

GY Lee, D You, H Lee, SW Hwang, C Justin Lee, YD Yoo

Journal of Cell Biology 217(6):2059-2071 (2018)

doi.org/10.1083/jcb.201709001

Mitochondria function as the cell’s power plant, where numerous ion channels and transporters work in harmony. This study reveals that Romo1, previously known as a mitochondrial reactive oxygen species modulator, is a non-selective monovalent cation channel with structural and functional traits akin to class II viroporins. This study not only redefines our understanding of Romo1’s role but also uncovers a novel class of mammalian ion channels resembling viral ion channels.

2017

2016

2012

2011