A joint research team from the Catholic University of Korea and Sungkyunkwan University has revealed the secret of the antibiotic shield of the super bacteria 'Pseudomonas aeruginosa.' 

- Pseudomonas aeruginosa Outer Membrane Blocking Large Pathway Found 'Caps' Protein...Presenting a New Target for Antibiotic Resistance Overcoming Research 

- Clarify the three-dimensional binding structure of protein caps with cryogenic electron microscopy (Cryo-EM) 

- Results of international joint research led by domestic researchers, 'Nature Communications (IF=15.7)' published

Picture description: (From left) Co-corresponding author Chung Jung-min of the Department of Biotechnology at Catholic University, Professor Cho Hong-baek of the Department of Bioscience at Sungkyunkwan University, and Co-first authors, Dr. Oh-hyun Kwon and Ye-seul Lee, integrated students in the Department of Biotechnology at Catholic University, and Dr. Beom-han Ryu of the Institute of Basic Science

 Through a joint study with Professor Cho Hong-baek of Sungkyunkwan University's Life Sciences Department, a team led by Professor Chung Jung-min of the Department of Biotechnology at Catholic University (President Choi Jun-kyu) identified a new molecular mechanism in which the representative super bacteria, Pseudomonas aeruginosa, blocks the inflow of external antibiotics by itself, setting a new turning point for the treatment of incurable infectious diseases.

 Pseudomonas aeruginosa, which causes infections, pneumonia, and sepsis in hospitals, is a representative gram-negative pathogenic bacterium that is extremely difficult to treat antibiotics because it has a hard outer membrane barrier. Pseudomonas aeruginosa forms a large protein passage called PilQ secretin on the outer membrane to assemble Type IV pilus, which is involved in surface attachment and mobility during the infection process. However, these outer membrane passages can be vulnerable to the inflow of external substances such as antibiotics if the assembly state is incomplete or not properly connected to the inner membrane complex. It is not clear how the bacteria prevent damage to the outer membrane barrier while maintaining the outer membrane passage necessary for the assembly of the fimbriae.

 The joint research team found a protein cap that seals the passage as a key to resolving this contradiction. As a result of the study, it was found for the first time that two proteins, "SlkA" and "SlkB," bind inside the PilQ channel and physically block the passage like a "plug." In fact, in the absence of SlkA and SlkB, antibiotic inflow through the PilQ passage increases and Pseudomonas aeruginosa becomes more vulnerable to antibiotics, especially in the absence of SlkA and SlkB.

 Among them, a research team led by Professor Jeong Jeong-min of Catholic University succeeded in visualizing the three-dimensional complex structure in which SlkA and SlkB proteins are bound inside the PilQ channel with high resolution using Cryo-EM, a cutting-edge bio-equipment. Existing academia estimated that the structural gate of the PilQ channel itself would block the inflow, but this study proved a new mechanism that a separate protein cap occupies the inside of the PilQ channel to complement the outer membrane defense function.

 This study is differentiated in that it identified the defense mechanism of antibiotic-resistant bacteria in multiple layers by connecting the three-dimensional structure of protein complexes and intracellular functions beyond gene-level phenomena. In addition, the binding site of the protein stopper and PilQ channel found by the research team is expected to be a new target for the development of antibiotic adjuvant that maximizes penetration of existing antibiotics in the future.

 The study was led by a joint research team from Catholic University and Sungkyunkwan University, and is an international joint research result involving Harvard Medical School, Michigan University, and UCLouvain. The paper, which was co-authored by Dr. Kwon Oh-hyun of Catholic University, Dr. Lee Ye-seul, integrated student of stone foil, and Dr. Ryu Bum-han of the Institute of Basic Science, was published in "Nature Communications (IF=15.7), a world-renowned author in the field of life science (DOI: 10.1038/s41467-026-73864-w).

 We are pleased to clearly demonstrate at the structural biology level the basic knowledge of treatment strategies to control superbacterial infections, a global health challenge, said Chung Jung-min, a professor of biotechnology at Catholic University. "In the future, we will further investigate the opening and closing mechanisms of bacterial outer membrane passages in the cell environment and accelerate follow-up studies such as searching for candidate substances to overcome antibiotic resistance."

This study was carried out with the support of the National Research Foundation of Korea (NRF) excellent research (task number RS-2022-NR071689). 

(Figure 1) Major antibiotic resistance threat cases presented by the U.S. Centers for Disease Control and Prevention (CDC). Multidrug-resistant P. aeruginosa is classified as one of the major antibiotic-resistant pathogens associated with hospital infections.

(그림2) (Figure 2) A conceptual diagram of PilQ secretin outer membrane passages blocked by SlkA or SlkB protein plugs during Pseudomonas aeruginosa Type IV pilus assembly. SlkA/B occupies PilQlumen before the inner membrane complex is docked, limiting the inflow of external substances.

(Figure 3) Comparison of the three-dimensional complex structure and actual alignment of protein stoppers in the outer membrane passage identified by ultracold electron microscopy. The Slk plug density observed in the purified protein complex is in good agreement with the PilQ lumen center density observed during intracellular Type IV pilus assay.