Journal of Microbiology

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PhoU interaction with the PhoR PAS domain is required for repression of the pho regulon and Salmonella virulence, but not for polyphosphate accumulation: Seungwoo Baek, Soomin Choi, Yoontak Han, Eunna Choi, Shinae Park, Jung-Shin Lee, Eun-Jin Lee; J. Microbiol. 2025;63(9):e2505013. Published online September 30, 2025; DOI: https://doi.org/10.71150/jm.2505013

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Abstract PDF Supplementary Material: The pho regulon plays a critical role in maintaining phosphate homeostasis in bacteria, with the PhoU protein functioning as a regulator that bridges the PhoB/PhoR two-component system and the PstSCAB₂ phosphate transporter. While PhoU is known to suppress PhoR autophosphorylation under high phosphate conditions via interaction with its PAS domain, its broader regulatory functions remain elusive. Here, we investigated the role of the PhoU Ala147 residue in Salmonella enterica serovar Typhimurium using a phoU^A147E substitution mutant. Bacterial two-hybrid and immunoprecipitation assays confirmed that Ala147 is essential for PhoU-PhoR PAS domain interaction, and its substitution leads to derepression of pho regulon genes, even in high phosphate conditions. This disruption impaired Salmonella survival inside macrophages and mouse virulence, demonstrating the importance of PhoU-PhoR interaction in Salmonella pathogenesis. However, unlike the phoU deletion mutant, the phoU^A147E mutant does not exhibit growth defects or polyphosphate accumulation, indicating that the PhoU-PhoR interaction is not involved in these phenotypes. Our findings reveal PhoU as a multifaceted regulator, coordinating phosphate uptake and pho regulon expression through distinct molecular interactions, and provide new insights into its role in bacterial physiology and virulence.

Journal Articles

Pat- and Pta-mediated protein acetylation is required for horizontallyacquired virulence gene expression in Salmonella Typhimurium: Hyojeong Koo , Eunna Choi , Shinae Park , Eun-Jin Lee , Jung-Shin Lee; J. Microbiol. 2022;60(8):823-831. Published online May 27, 2022; DOI: https://doi.org/10.1007/s12275-022-2095-y

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Salmonella Typhimurium is a Gram-negative facultative pathogen that causes a range of diseases, from mild gastroenteritis to severe systemic infection in a variety of animal hosts. S. Typhimurium regulates virulence gene expression by a silencing mechanism using nucleoid-associated proteins such as Histone-like Nucleoid Structuring protein (H-NS) silencing. We hypothesize that the posttranslational modification, specifically protein acetylation, of proteins in gene silencing systems could affect the pathogenic gene expression of S. Typhimurium. Therefore, we created acetylation-deficient mutant by deleting two genes, pat and pta, which are involved in the protein acetylation pathway. We observed that the pat and pta deletion attenuates mouse virulence and also decreases Salmonella’s replication within macrophages. In addition, the Δpat Δpta strain showed a decreased expression of the horizontally-acquired virulence genes, mgtC, pagC, and ugtL, which are highly expressed in low Mg2+. The decreased virulence gene expression is possibly due to higher H-NS occupancy to those promoters because the pat and pta deletion increases H-NS occupancy whereas the same mutation decreases occupancy of RNA polymerase. Our results suggest that Pat- and Pta-mediated protein acetylation system promotes the expression of virulence genes by regulating the binding affinity of H-NS in S. Typhimurium.

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Reversible acetylation of ribosomal protein S1 serves as a smart switch for Salmonella to rapidly adapt to host stress
Yi-Lin Shen, Tian-Xian Liu, Lei Xu, Bang-Ce Ye, Ying Zhou
Nucleic Acids Research.2025;[Epub] CrossRef
Multi-Lasso Peptide-Based Synergistic Nanocomposite: A High-Stability, Broad-Spectrum Antimicrobial Agent with Potential for Combined Antibacterial Therapy
Yu Li, Jinyu Zhang, Ke Wei, Di Zhou, Zepeng Wang, Zhiwei Zeng, Yu Han, Weisheng Cao
ACS Nano.2024; 18(45): 31435. CrossRef

A rule governing the FtsH-mediated proteolysis of the MgtC virulence protein from Salmonella enterica serovar Typhimurium: Jonghyun Baek , Eunna Choi , Eun-Jin Lee; J. Microbiol. 2018;56(8):565-570. Published online July 25, 2018; DOI: https://doi.org/10.1007/s12275-018-8245-6

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Abstract PDF

A tightly controlled turnover of membrane proteins is required for lipid bilayer stability, cell metabolism, and cell viability. Among the energy-dependent AAA+ proteases in Salmonella, FtsH is the only membrane-bound protease that contributes to the quality control of membrane proteins. FtsH preferentially degrades the C-terminus or N-terminus of misfolded, misassembled, or damaged proteins to maintain physiological functions. We found that FtsH hydrolyzes the Salmonella MgtC virulence protein when we substitute the MgtC 226th Trp, which is well conserved in other intracellular pathogens and normally protects MgtC from the FtsH-mediated proteolysis. Here we investigate a rule determining the FtsHmediated proteolysis of the MgtC protein at Trp226 residue. Substitution of MgtC tryptophan 226th residue to alanine, glycine, or tyrosine leads to MgtC proteolysis in a manner dependent on the FtsH protease whereas substitution to phenylalanine, methionine, isoleucine, leucine, or valine resists MgtC degradation by FtsH. These data indicate that a large and hydrophobic side chain at 226th residue is required for protection from the FtsH-mediated MgtC proteolysis.

Citations

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Scientific Reports.2019;[Epub] CrossRef

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